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ISSN 0042-8817 (Russian ed. Print)ISSN 2313-8254 (English ed. Online)

ISSN 2309-1681 (Russian ed. Online)

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Vol. 80

PROBLEMS OF NEUROSURGERYnamed after N.N. Burdenko

FUNDAMENTAL AND PRACTICAL JOURNAL

EDITORIAL BOARD

Editor-in-Chief A.N. Konovalov Deputy Editor-in-Chief O.N. Dreval’ Executive Editor A.V. KozlovScience Editors B.A. Kadashev, O.B. Belousova

Burdenko Neurosurgical Institute, Moscow, RussiaOffi cial journal of the Association of Neurosurgeons of Russia

«Zhurnal voprosy neirokhirurgii imeni

N N Burdenko» (Problems of

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CONTENTS

© Media Sphera, 2016 2

ORIGINAL ARTICLES

Absalyamova O.V., Kobyakov G.L., Ryzhova M.V., Poddubskiy A.A., Inozemtseva M.V., Lodygina K.S.Outcomes of Application of Modern First-Line Chemotherapy Regimens in the Multimodality Therapy of Patients with Glioblastoma . . . . . . 4Gushcha A.O., Arestov S.O., Vershinin A.V.The First Experience with a New Technique of Portal Endoscopic Discectomy for Herniated Cervical Discs . . . . . . . . . . . . . . . . . . . . . . . . . . 13Astaf’eva L.I., Kadashev B.A., Shishkina L.V., Kalinin P.L., Fomichev D.V., Kutin M.A., Aref’eva I.A., Dzeranova L.K., Sidneva Yu.G., Klochkova I.S., Rotin D.L.Clinical and Morphological Characteristics, Diagnostic Criteria, and Outcomes of Surgical Treatment

of TSH-secreting Pituitary Adenomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Khabarova E.A., Denisova N.P., Rogov D.Yu., Dmitriev A.B.The Preliminary Results of Subthalamic Nucleus Stimulation after Destructive Surgery in Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . 32Kondrakhov S.V., Zakharova N.E., Fadeeva L.M., Tanyashin S.V.Phase Contrast MRI-based Evaluation of Cerebrospinal Fluid Circulation Parameters in Patients with Foramen Magnum Meningiomas . . . 37Kushel’ Yu.V., Belova Yu.D., Tekoev A.R.Application of Resorbable Plates for Fixation of a Laminotomy Flap . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49Dzhindzhikhadze R.S., Dreval’ O.N., Lazarev V.A., Kambiev R.L.Minipterional Craniotomy in Surgery for Anterior Circle of Willis Aneurysms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

CASE REPORTS

Savateev A.N., Konovalov A.N., Gorelyshev S.K., Satanin L.A., Khukhlaeva E.A., Shishkina L.V., Ozerova V.I., Valiakhmetova E.F., Medvedeva O.A.A Giant Hyperostotic Parasagittal Meningioma in a Child with Neurofibromatosis Type II. A Case Report and Literature Review . . . . . . . . 59Martynova M.A., Konovalov N.A., Lubnin A.Yu., Shmigel’skiy A.V., Savin I.A., Tabasaranskiy T.F., Akhvlediani K.N., Sinbukhova E.V., Onoprienko R.A.Spinal Stroke in a Pregnant Female with an Endodermal Cyst of the Cervical Spinal Cord (a Case Report and Literature Review) . . . . . . . . . 67Goroshchenko S.A., Ivanov A.Yu., Rozhchenko L.V., Ivanova N.E., Zabrodskaya Yu.M., Razmologova O.Yu., Kondrat’ev A.N., Potemkina E.G., Dmitrievskaya A.Yu., Blagorazumova G.P., Radzhabov S.D., Petrov A.E., Ivanov A.A., Sinitsyn P.S., Bobinov V.V.Extrapontine Myelinolysis Developed After Aneurysmal Subarachnoid Hemorrhage (a Case Report and Literature Review) . . . . . . . . . . . . . 74Konovalov N.A., Shishkina L.V., Asyutin D.S., Onoprienko R.A., Korolishin V.A., Zakirov B.A., Martynova M.A., Cherkiev I.U., Pogosyan A.L., Timonin S.Yu.Extradural Spinal Cord Hemangioblastoma (a Case Report and Literature Review) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79Vasin R.A., Krasnikov M.A., Vasina S.V.Infant Form of Alexander Disease (Clinical Case and Literature Review) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

GUIDELINES FOR THE PRACTITIONER

Shimanskiy V.N., Karnaukhov V.V., Tanyashin S.V., Poshataev V.K., Shevchenko K.V., Odamanov D.A., Kondrakhov S.V.Use of Surgical Approaches to the Posterior Cranial Fossa in Patients in a Lying Position. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

REVIEWS

Shurkhay V.A., Goryaynov S.A., Aleksandrova E.V., Spallone A., Potapov A.A.Navigation Systems in Neurosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

Zav’yalov D.M., Peretechikov A.V.Prevention and Treatment of Postoperative Epidural Scar Adhesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105

3

In accordance with the resolution of the Higher Attestation Commission of the Ministry of Education and Science of theRussian Federation, the Problems of Neurosurgery named after N.N. Burdenko was included in the List of Leading PeerReviewed Journals and Periodicals issued in the Russian Federation where the main results of Candidate and Doctor Theses are recommended to be published.

Topics to be covered in our next issue:

● The current status of neurosurgical services in the Russian Federation

● Anatomy of the neural pathways of the brain

● Clinical recommendations for management of acoustic neuromas

4 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

ORIGINAL ARTICLES

© Group of authors, 2016

doi: 10.17116/engneiro20168064-12

Outcomes of Application of Modern First-Line Chemotherapy Regimens in the Multimodality Therapy of Patients with GlioblastomaO.V. ABSALYAMOVA, G.L. KOBYAKOV, M.V. RYZHOVA, A.A. PODDUBSKIY, M.V. INOZEMTSEVA, K.S. LODYGINA

Burdenko Neurosurgical Institute, Moscow, Russia

Objective. The objective of this study is to describe the procedure and outcomes of comprehensive first-line treatment in glioblastoma patients.Material and methods. We analyzed 107 glioblastoma patients who were operated on in 2010—2011. Seventy five patients underwent combined chemoradiotherapy (CRT) with simultaneous administration of 75 mg/m2 temozolomide (TMZ) followed by chemotherapy with 200 mg/m2 TMZ for 5 days, every 28 days. Separately, we examined 32 patients with large tumors, who received alternative treatments.Results. The median time to progression was 11.7 months in the study group and 7.2 and 8.1 months in the groups of alternative therapy. The one-year progression-free survival rate was 37%. Overall survival was 29.2 months.Conclusion. The chemoradiotherapy regimen involving TMZ followed by one-year TMZ monotherapy is an appropriate treatment for patients who underwent glioblastoma resection. With this approach, no tumor progression occurs in one third of patients during the first year. Thorough study of clinical and radiological findings in the course of treatment makes it possible to achieve maximum efficacy, avoid unreasonably early switch to second-line therapy, and timely detect tumor recurrence signs. The Response Assessment in Neuro-Oncology (RANO) criteria should be used to assess MRI-detected changes in the tumor size. The rates of overall and recurrence-free survival were significantly lower in patients with inoperable or partially resected tumors. The applied approaches provide only a slight advantage in tumor growth control, which necessitates the search for more effective treatment options for these patients. Inclusion of bevacizumab to the first-line therapy regimen may be a possible approach.

Keywords: glioblastoma, chemotherapy, evaluation criteria, tumor pseudoprogression.

e-mail: [email protected]

Glioblastoma (GB) is the most common primary

malignant tumor of the central nervous system in adults,

whose incidence is 20%. GB is characterized by an

extremely unfavorable prognosis: in most patients,

progression of the disease is detected within the first year

after surgery; overall survival (OS) did not exceed 1 year

for a long time [1]. Currently, a comprehensive approach

is used to treat GB patients, including surgery,

radiotherapy (RT), and chemotherapy (CT) and life

expectancy is up to 2 years.

Maximum possible tumor resection followed by a

combination of chemoradiotherapy (CRT) with

temozolomide (TMZ) and subsequent adjuvant

chemotherapy (TMZ) is the “gold standard” of the first-

line treatment of patients with GB. RT is applied on the

tumor area (including about 2―3 cm around it) at a total

dose of 60 Gy and single dose of 2 Gy along with

administration of TMZ (75 mg/m2). Chemotherapy with

TMZ at a unit dose of 200 mg/m2 is started 28 days after

completion of this treatment (during 5 days followed by

23-day break). This regimen was first described by R.

Stupp et al. [2], who have shown that inclusion of TMZ

in this treatment regimen increases the median time to

progression (MTTP) from 5 to 6.9 months, and OS from

12.1 to 14.6 months as compared to the group of patients

treated with radiation therapy alone. According to the

study by M. Gilbert et al. [3], which was completed in

2013, MTTP was 8.8 months, and OS was 18.9 months,

when using this regimen.

This study was aimed at evaluating the overall and

disease-free survival of 107 patients with morphologically

verified glioblastoma, who were treated at the Burdenko

Neurosurgical Institute in 2010—2011.

Materials and methods

We analysed treatment outcomes of 107 patients

with morphologically verified GBs, who were operated

on in 2010—2011 and followed on a regular basis at the

Burdenko Neurosurgical Institute. We retrospectively

analyzed the results of everyday work, when the decision

was made in each case in accordance with modern

standards of GB treatment with allowance for individual

characteristics, such as tumor size, general status, and

presence of intracranial hypertension.

A total of 75 patients underwent a combined CRT

with simultaneous administration of TMZ at a dose of 75

mg/m2 followed by CT with TMZ at a dose of 200 mg/

m2 for 5 days and then a 23-day break. Patients, who

postoperatively had large residual tumors, received the

combined chemoradiotherapy followed by CT with TMZ

at a dose of 150 mg/m2 from the 1st to 5th day of treatment

session + Carboplatin 300 mg/m2 on the first day of the

course; treatment courses repeated every 28 days

(treatment regimen with TMZ and Carboplatin, TC).

There were a total of 20 such patients. The average

number of CT courses in both groups was 6.2, from 0 (7

patients) to 21 (2 patients) courses. Twelve patients did

not receive RT. This decision was taken in patients, who

postoperatively had persisting signs of intracranial

hypertension in the fundus and/or very large tumor

(tumor remnants) accompanied by shift of midline

5PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

structures. These patients underwent CT in TC mode; in

the case of regression of intracranial hypertension signs

and decrease in tumor signs, RT was performed in

combination with CT. Postoperative treatment was

carried out at the Burdenko Neurosurgical Institute and

Oncology Centers in Moscow and other regions of

Russian Federation.

General information about the patient is shown in

Table 1.

Tumor size dynamics was assessed based on the

archival data of contrast-enhanced MRI of the brain

performed before CRT, 1 month after completion of the

CRT, and then after every 3 CT courses. Upon

completion of treatment, MRI was performed every 3—5

months and in the case of clinical signs of tumor

progression and evaluated according to RANO (Response

Assessment in Neuro-Oncology International Group)

criteria.

Results

At the time of data analysis, progression of the disease

was observed in 91 (85%) of 107 patients. Progression-

free survival for more than 1 year was observed in 37%

(40 patients). Progression-free survival for 12—18

months was observed in 17 (15.8%) patients, PFS for

18—24 months was observed in another 12 (11.2%)

patients, more than 24 months — 11 patients (10 — up to

3 years and 1 — more than 3 years). Regardless of

treatments, MTTP was 10.3 months, OS — 29.2 months.

In treatment groups, MTTP was as follows: combined

CRT with TMZ followed by therapy with TMZ — 11.7

months; combined CRT with TMZ followed by TC

treatment — 7.2 months; patients who started CT

possibly followed by RT — 8.1 months (p=0.008) (Fig. 1).

Overall survival was 33.3, 26.3, and 18 months,

respectively (p=0,007).

Discussion

Objective of the study was to assess treatment

outcomes of patients with glioblastoma, using high-level

surgical techniques, modern RT techniques, and

sufficient number of modern CT courses.

The number of followed patients

We describe treatment outcomes of only 107 patients,

which accounts for 31.4% of all patients, who were for

the first time operated on for GB at the Burdenko

Neurosurgical Institute in 2010—2011. Relatively small

number of patients included in the analysis was due to

both loss of medical history and failure to comply with

GB treatment standards [4]. Our findings are consistent

with data of A.V. Smolin et al., who conducted the

Russian multi-centered study on the epidemiology of

malignant gliomas from 01.01.2012 to 31.12.2013. This

study included 325 patients from 29 medical centers in

Russia. It has been shown that only every fourth patient

received combined CRT and 1/3 of patients received no

first-line CT. Among the patients who received first-line

CT, some patients received medications other than

TMZ [5].

Thus, higher numbers of MTTP obtained in this

study were due to the use of modern glioblastoma

treatment regimens. Furthermore, patients who did not

receive treatment, did not request re-consultation, those

who were unavailable for history taking and possibly died

in the early postoperative period, were not included in

our study.

Combined chemoradiation therapy with temozolomide followed by adjuvant therapy with temozolomide

In the study group, MTTP was 11.7 months. In

patients, who were treated at the Burdenko Neurosurgical

Institute using an identical regimen in 2006—2007,

MTTP was 9.7 months [6].

In world practice, the standard CRT mode with

TMZ followed by treatment with TMZ includes only 6

CT courses.

However, some clinicians are inclined to the opinion

that larger number of courses are advisable, especially in

patients with contrasted tumor remnants. There were no

comparative randomized trials assessing the effectiveness

of this approach. When comparing suitable groups from

various studies, the following results were obtained. In

the study by M. Stupp et al. [2], MTTP was 6.9 months in

the group of patients, who received CRT + 6 courses of

TMZ; in the study by Chinot O. et al. [7], MTTP was 6.2

months in the group of CRT + 6 courses of TMZ; in the

study by M. Gilbert et al. [4], MTTP was 8.8 months in

Table 1. General information about 107 patients with glioblastoma

Combination therapyCRT + TMZ, abs.

(%)

CRT + TC, abs.

(%)TC +/- RT, abs. (%) Total, abs. (%)

Number of patients 75 (70) 20 (18,7) 12 (11,3) 107

Males 37 (49,4) 8 (40) 7 (58,4) 52 (49)

Females 38 (50,6) 12 (60) 5 (41,6) 55 (51)

Average age, years 49 47 48 —

Local lesion 74 (98) 19 (95) 8 (66,6) 101 (94)

Multiple lesions 1 (2) 1 (5) 4 (33,4) 6 (6)

Tumor resection 75 (100) 19 (95) 9 (75) 103 (96,2)

Biopsy 0 1 (5) 3 (25) 4 (3,8)


ORIGINAL ARTICLES

the group of patients who received CRT + 12 courses of

TMZ. It should be noted that in the study of R. Stupp et

al., 16—17% of patients underwent only tumor biopsy, in

the study of Chinot O. et al., the proportion of biopsies

was 9.5—13.1%, M. Gilbert — 3%. Thus, it is still unclear

what exactly has determined increase in MTTP, either

longer CT or radical tumor resection.

In our series, 3.8% of patients underwent only tumor

biopsy. When prescribing more than 6 CT courses, we

were primarily guided by tolerability of therapy and the

presence of residual tumor. If therapy was tolerated

satisfactorily (blood parameters), we continued treatment

up to 10 courses. Retrospective analysis has shown that

51 patients had no progression after CRT and 6 CT

courses. In the cases, where CT was stopped or continued,

MTTP was 17.7 and 17.3 months, respectively, the

differences are not significant (p=0.512) (Fig. 2). When

extending CT for more than 10 courses, we were guided

by the presence of contrasted tumor remnants, absence

of progression signs during continued treatment, as well

as increased metabolic activity in a tumor as shown by

positron emission tomography (PET) of the brain with

C11 methionine. In 20 patients without progression after

10 CT courses, MTTP was 26.4 months in the cases when

CT was termination, and 19.2 months when it was

continued over 10 courses (p=0.015) (Fig. 3). The

differences were not significant. This results lead to

conclusion that these patients require continued

antitumor therapy, by probably in other regimens.

Bevacizumab in the first-line therapy for GB

The study of Cloughesy was one of the first researches

that provided the basis for the use of bevacizumab (Bev)

in patients with GB progression. The study described 167

patients with GB relapse, who were treated with Bev or

Bev in combination with irinotecan. Partial response

(tumor reduction by 50% or more) was achieved in 28.3%

of patients who received Bev and 37.8% of patients who

received Bev + irinotecan; in several patients, complete

response was achieved. We obtained similar results in 36

patients with GB relapse, who received combinations of

various cytostatics with Bev (in Russian Federation, Bev

was approved for the treatment of GB since November

2009). Partial response was achieved in 13 patients,

complete response – 3 patients [9].

According to the results of Avaglio and RTOG 0825

studies, application of Bev in the first-line treatment in

addition to R. Stupp’s regimen increases the MTTP, but

does not affect the OS. For example, MTTP was 6.2

months in patients, who were included in Avaglio and

used CRT regimen with TMZ. When this regimen was

supplemented with Bev at a dose of 10 mg/kg every 2

weeks starting from the first day of the CRT and further

until progression, MTTP was 10.8 months. OS was 16.7

and 16.8 months, respectively [7]. Such a difference in

the effect of Bev on the MTTP and OS was due to the fact

that patients, who did not receive Bev in the first line

treatment, received it in the second-line treatment and

for this reason OS was similar in both groups of patients.

Fig. 1. Median time to tumor progression in patients with glioblastoma who received various types of post-operative treatment.


Currently, Bev is not recommended as the first-line

therapy for GB.

Criteria to assess the efficacy of treatment of central nervous system tumors

When speaking of tumor progression, the criteria for

determining progression signs should be mentioned.

Since 1990, criteria suggested by D. Macdonald et al. [10]

were used in neuro-oncology for tumor evaluation. They

take into account tumor size, the presence of new lesions,

the dynamics of neurological symptoms, and the use of

steroid therapy. However, these criteria can not be used

to assess non-contrasted tumors, which is a drawback.

Another serious problem lies in the fact that Macdonald’s

criteria are used for the tumors subjected to therapy with

anti-angiogenic drugs (e.g., Bev), which change the

permeability of the capillaries and thereby inhibit tumor

contrasting. In this situation, the true spread of the tumor

can only be determined in the T2/FLAIR-mode. For this

reason, RANO [11] criteria are used since 2010. RANO

criteria assess tumor size over time using T1 contrast-

enhanced MRI and hyperintensive signal area using T2

and FLAIR modes and also take into account neurological

status and the use of dexamethazone (Table 2).

Case report

Here we provide a case report to illustrate our

treatment strategy.

Patient C., 40 years old. Since May 2012, the patient

experienced progressive headaches, there was an episode

of generalized seizure. MRI of the brain with intravenous

contrast performed on 26 May 2012 detected a mass

lesion of the right temporal lobe, actively accumulating

contrast and accompanied by a pronounced perifocal

edema (Fig. 4a). Tumor was resected on 02.07.12.

Histological examination identified GB. In July —

August 2012, the patient underwent CRT: RT single dose

of 2—3 Gy, total dose of 48 Gy (unfortunately, in some

institutions in the Russian Federation, non-standard

single-dose radiation therapy is used in the treatment of

patients with brain tumors) with simultaneous oral intake

of TMZ at a dose of 140 mg daily. MRI in September

2012 detected no contrasted tumor remnants (see

Fig. 4b). During the period from September 2012 to July

2013, the patient underwent 11 courses of chemotherapy

with oral intake of TMZ at a dose of 400 mg for 5 days

every 28 days. MRI in July 2013 detected no contrasted

tumor remnants (see Fig. 4c). In July 2013, PET of the

brain with C11 methionine detected the area with

enhanced accumulation of radiopharmaceutical,

accumulation index (AI) 1.62, tumor remnants with

moderate metabolic activity. Due to this fact, CT with

TMZ was continued and a total of 17 courses were

conducted by February 2014. Patient's condition was

satisfactory, steroid therapy was not carried out, seizures

did not recur, and the patient returned to work. During

the period from February 2014 to September 2015 (20

months), chemotherapy was not carried out. Scheduled

MRI in September 2015 (38 months after surgery)

detected increased area of hyperintensive signal in

FLAIR mode at the surgical area and in the right pole of

the temporal lobe. There was no worsening of neurological

symptoms. On 28.09.15, PET detected hypermetabolic

area with AI of 2.05 at the pole of the temporal lobe in

accordance with the changes detected by MRI, continued

tumor growth (see Fig. 4c). During the period from

Fig. 2. Median time to tumor progression in GB patients, who received 6 cycles of TMZ and more.


ORIGINAL ARTICLES

19.10.15 to 21.10.15, the patient underwent stereotactic

radiotherapy using hypofractionation regimen at the area

of tumor recurrence in the right temporal lobe, including

3 mm margin around this area (GTV/CTV 2.969/5.612

cm3), a total of 3 fractions, 8 Gy per fraction until average

total dose of =24.82/24.1 Gy using multiple beams

method (A=145), until total dose of 21.5 Gy prescribed

at the isodose of 81%. TMZ chemotherapy was resumed

from October 2015 to March 2016, a total of 6 courses

were carried out. In February 2016 (44 months after

surgery), MRI showed decrease in the hyperintensive

signal area in FLAIR mode at the pole of the right

temporal lobe and stable pattern at the surgical area. PET

of the brain with C11 methionine: decreased

accumulation of the radiopharmaceutical, AI 1.23 (see

Fig. 5d). There was no worsening of neurological status.

Headache and seizures did not recur since the surgery. At

the time of writing of this article, 48 months have elapsed,

there is no signs of disease progression.

Pseudoprogression

“Pseudoprogression” term was first suggested in

2007. Pseudoprogression (PsP) is a name for subacute

changes, developing within 12 weeks after RT and

characterized by X-ray picture of increase in contrasted

area by more than 25%. It is believed that combined CRT

with TMZ increases the incidence of PsP phenomenon.

Despite the MR-signs of disease progression, spontaneous

regression of both clinical symptoms and contrasted area

(MRI) is subsequently observed in some of these patients.

The incidence of PsP averages 20—30%. It was shown

that development of PsP correlates with methylated

MGMT gene in the tumor and may be a predictor of high

efficacy of the therapy [12]. Therefore, the use of the

aforementioned evaluation criteria is relevant no earlier

than 12 weeks after completion of RT. Before that time,

appearance of new lesions outside the irradiated area is

the main symptom of tumor progression.

For clinicians, pseudoprogression phenomenon

causes doubts in the choice of further treatment strategy.

On the one hand, when ignoring the PsP phenomenon

and changing treatment schedule, we deprive a patient of

the possibility to continue effective and convenient

therapy with TMZ. On the other hand, true progression

is much more common, and in this case, continuation of

previous therapy is inadvisable. A number of

investigators [13] “modify” pseudoprogression criteria,

considering as PsP only those cases, where increase is

contrasted area is not associated with worsening of

symptoms and the time acceptable for PsP diagnosis does

not exceed 1 month after chemoradiotherapy.

It is highly important to distinguish between true

progression and pseudoprogression, when planning a

second-line therapy of GB. False-high effectiveness

values can be obtained when including PsP patients in

the study.

In our series, we observed increase in contrasted area

by more than 25% within the period of 160 days after

diagnosis, i.e. about 12 week after completion of CRT, in

17 patients (10 of these patients continued treatment).

Seven (41%) of 17 patients survived for more than 1 year

after detection of progression. At the time of writing of

this article, 6 patients died and 1 patient is alive; overall

survival in this group is 22 to 66 months (average survival

is 33 months). Most likely, these 7 patients had

pseudoprogression phenomenon.

Metabolic, perfusion, diffusion, and X-ray studies

can be used to distinguish between progression and

pseudoprogression. Further studies are required to

investigate reliability and procedure of their use [12].

Fig. 3. Median time to tumor progression in GB patients, who received 10 courses of TMZ and more.


Patients with large and inoperable GBs

In 2009, the study “Chemotherapy in the treatment

of patients with inoperable malignant supratentorial

astrocytic gliomas” was completed at the Burdenko

Neurosurgical Institute. In this study, 37 patients with

inoperable large GBs, who underwent only STB followed

by CT, were treated using three regimens: PCV was used

in 15 (40.5%) patients, TMZ — 5 (13.5%), TMZ +

cisplatin — 17 (54%) patients. MTTP was 5, 4, and 8

months, median OS — 8.5, 6.0, and 10.5 months,

respectively. In the cases, where only CT was applied, the

highest direct effectiveness was obtained when using the

TMZ + cisplatin regimen: complete response was

observed in 2 patients, partial response — 10,

stabilization — 7, and progression — 7. When using

monotherapy with TMZ, stabilization was the maximum

effect [14].

The study of combination of TMZ + cisplatin was

preceded by a series of studies performed in patients with

recurrent GB. The study by A. Brandes et al. [15] was the

first and the largest series of cases that showed the efficacy

of the combination of TMZ + cisplatin in patients with

recurrent GB, who were not previously treated with CT.

The investigation was based on in vitro study, showing

that cisplatin is capable of not only reducing activity of

MGMT, but also enhancing the efficacy of TMZ in this

direction. Additionally, the efficacy of combination

TMZ + cisplatin as the first-line treatment was shown in

patients, who already received TMZ and thereafter had

PROP [16]. S. Balana et al. [17] have shown the

effectiveness of the use of TMZ + cisplatin as the first-

line treatment in patients with verified inoperable GB.

We used carboplatin instead of cisplatin in

combination with TMZ in this group of GB patients.

Carboplatin is less nephrotoxic and significantly less

emetogenic.

In 792 patients with advanced ovarian cancer,

combination carboplatin + paclitaxel was no less effective

than combination cisplatin + paclitaxel, had fewer side

effects and more convenient administration regimen

[18]. When comparing the effectiveness of combinations

bleomycin + etoposide + carboplatin or cisplatin (BEC/

BEP), it was shown that BEP is essentially superior to

BEC in terms of relapse-free and overall survival [19].

Previous treatment of 618 patients with disseminated

non-small cell lung cancer using carboplatin + paclitaxel

or cisplatin + paclitaxel modes showed that, while the

number of responses to treatment was similar, OS of

patients was higher in the case of the combination

cisplatin + paclitaxel, and carboplatin + paclitaxel

combination is a reasonable alternative, with the same

response rate, good safety profile, acceptable toxicity,

and ease of application [20]. No comparative evaluation

of the efficacy of the combinations cisplatin + paclitaxel

and TMZ + carboplatin was carried out in patients with

inoperable gliomas.

In our series, 12 patients received only CT as a first-

line therapy. Multifocal GBs were detected in 4 patients,

STB was performed in one of them and the rest underwent

resection of one tumor node. Disseminated diffuse GB

was observed in 8 patients. STB was done in 2 cases,

partial tumor resection — 6. In all cases, the size of the

original tumor or tumor remnants after resection

excluded the possibility of RT. These 12 patients received

CT in the TC mode. Six patients underwent RT after

tumor size reduction. MTTP was 8.1 months in the entire

group.

Based on the available data on the effectiveness of

TMZ in combination with platinum preparations in

patients with large GBs, we administered TC after

completion of CRT in patients with partially resected

GBs, a total of 20 patients. Of these, tumor progression

before completion of 6 CT courses was observed in 16

patients. Four patients continued treatment for more

than 6 courses, including 3 patients who had progression

after 8, 9 and 12 courses, respectively. The treatment was

Table 2. Criteria to assess the dynamics of central nervous system tumors

Complete response Partial response Stabilization Progression

*M **R M R M R M R

Contrasted foci

in T1 mode

No No Decrease

by 50% and

more

compared

to the

baseline

Decrease

by 50% and

more

compared

to the

baseline

Any other

situation

Any other

situation

Increase by

25% and

more

compared

to the

baseline

Increase by

25% and

more

compared to

the baseline

T2/FLAIR Not

considered

Stable or

decrease

Not

considered

Stable or

decrease

Not

considered

Stable or

decrease

Not

considered

Increase

significantly

New foci No No No No No No Yes Yes

Corticosteroids No No Stable or

decrease

Stable or

decrease

Stable or

decrease

Stable or

decrease

Any Any

Clinical status Stable or

improved

Stable or

improved

Stable or

improved

Stable or

improved

Stable or

improved

Stable or

improved

Worsened Worsened

Considered in

evaluation

All All All Any of the above

Note: *Macdonald’s criteria; **RANO criteria.


ORIGINAL ARTICLES

stopped after 10 courses in 1 patient. The median time to

progression in this group was 7.2 months.

Historical data show that patients with inoperable

GBs who receive only symptomatic therapy survive for

about 3 months, while those who receive radiotherapy

survive for 6—7 months [21]. Therefore, temozolomide +

cisplatin and TMZ + carboplatin regimens can be

recommended for the use in patients with disseminated

diffuse glioblastoma. However, in spite of the improved

OS, the results of treatment of patients with large GBs

remain unsatisfactory.

Early tumor progression in these patients is indicative

of relatively low efficacy of therapy and the need for more

effective medications, for example, Bev.

As mentioned above, the results of randomized phase

III studies show that Bev is not indicated in the first-line

treatment of GB. However, data analysis by O. Chinot

have shown that the use of Bev in the first-line treatment

has different effects on survival of patients with various

subtypes of GB. Thus, in patients with proneural GB and

no mutations of IDH1 gene, who received Bev in the

first-line treatment, OS was 17.1 months, while in the

placebo group it was 12.8 months (p = 0.002) [22]. It was

also shown that the use of Bev resulted in significantly

longer time to worsening of overall health status, physical

and social functioning, communication, and motor

deficits. It was reported that Bev can effectively reduce

the cerebral edema [23].

It should also be noted that the criteria for inclusion

of patients to Avaglio and RTOG 0825 implied that they

have Karnofsky score of 70 or higher, while the majority

of patients in our series who received TC had a lower

score. Thus, taking into account high direct efficacy of

Bev, which was detected both clinically and in MRI

studies, it is reasonable to examine its efficacy in the first-

line treatment of patients with diffuse disseminated GB.

The factors, predicting beneficial effect of Bev, such as

GB subtype, serum level of matrix metalloproteinase,

and methylation status of the MGMT gene, should be

studied.

Fig. 4. Example of treatment of a patient with glioblastoma of the right temporal lobe.Explanation in the text.

1, a — preoperative MRI; 1,b — MRI 2 months after surgery; 2 — MRI one year after surgery; 3 — PET and MRI 38 months after surgery, tumor progression; 4 — PET

and MRI 44 months after surgery, positive dynamics.


Conclusion

Chemoradiation therapy with temozolomide

followed by a year-long temozolomide monotherapy is

an optimal treatment regimen for patients who underwent

resection of GB. A third of patients treated using this

approach have no signs of tumor progression during the

first year. Thorough study of clinical and radiological

findings in the course of treatment makes it possible to

achieve maximum efficacy, avoid unreasonably early

switch to second-line therapy, and timely detect tumor

recurrence signs. The Response Assessment in Neuro-

Oncology (RANO) criteria should be used to assess

MRI-detected changes in the tumor size. The rates of

overall and recurrence-free survival were significantly

lower in patients with inoperable or partially resected

tumors. The applied approaches provide only a slight

advantage in control of tumor growth, which necessitates

the search for more effective treatment options for these

patients. Inclusion of bevacizumab to the first-line

therapy regimen may be a possible approach.

Commentary

This work focuses on an obviously important issue,

the treatment of patients with brain glioblastomas.

Strength of this study lies in the analysis of authors’ own

results of treatment of patients in their routine practice,

careful follow-up history taking, thoughtful analysis of

the results, and the use of both international and Russian

studies in their discussion. The authors collected

information about 107 patients treated at the Burdenko

Neurosurgical Institute in 2010—2012. Treatment of

glioblastomas is expensive, and for this reason in does not

meet international standards in a significant number of

cases in Russia. The situation, when a large number of

patients were treated at the same institution in full

compliance with its standards, is quite rare. However, as

shown in this study, this approach enables not only

reproducing, but also going beyond the results of

treatment obtained in the world’s best clinics. The

authors’ findings, demonstrating that there is no need to

increase the number of temozolomide chemotherapy

courses to more than six, is important from a practical

viewpoint.

A.V. Smolin (Moscow, Russia)

There is no conflict of interest.

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The incidence of cervical discogenic compression

syndromes is extremely high. According to J. Lawrence [1],

despite the relatively small proportion of detectable

lesions of the cervical intervertebral disc among the total

number of degenerative spinal diseases, about 10% of the

population experience periodic compression-related pain

in the cervical spine or in the hand.

Assessment of cervical hernia is based on conventional

staging classification of intervertebral disc herniation

(protrusion, prolapse, and sequester) proposed by

A. Decoulx [2], which is important in evaluation of the

clinical course of the process and selection of treatment

strategy, as well as classification of herniated intervertebral

discs in terms of their axial arrangement and relationship

with the bony structures of the spinal canal. The latter

distinguish between median, paramedian (laterally shifted

with respect to the sagittal plane), lateral, and foraminal

hernia.

Based on the analysis of a large number of cases,

J. Bland et al. [3] determined characteristic clinical

symptoms associated with cervical radicular compression,

having practical value to assess the severity of impairment

and axial arrangement of hernia. Along with the

characteristic radicular irradiation of pain, sensory

disturbances, loss of tendon reflexes corresponding to

innervated myosclerotome, and paresthesia, which are

indicative of root compression in the intervertebral

foramen, are often detected. In the case of questionable

data, Spurling’s test is recommended (axial load on the

neck along with side-to-side shaking), which leads to

worsening of paresthesia [4].

J. Knightly [5] conveniently distinguish two

pathoanatomical type of compression substrate formation

at the level of intervertebral disc: soft disc (or fragments of

prolapsing disc as the acute phase of the disease) and hard

disc (uncovertebral osteophytes as the chronic phase of

the disease). In our opinion, the structural state of the

compressing factor, as well as its axial arrangement is the

key factor in in the choice of surgical treatment. In

patients with “soft disc”, clinical presentation is

dominated by symptoms of brachialgia that often occur

after physical activity, sudden movement of the head, or

neck injury. Irradiation of acute radicular pain

corresponds to dermatomes and often depends on the

position of the head and limbs. “Helmet”-like or

homolateral hemicrania-like irradiation of the pain is

very typical for this group of patients. Hypesthesia,

accompanying this kind of compression, always involve

individual dermatomes and may be accompanied by an

isolated reduction of tendon reflexes in adjacent muscles.

Decrease in strength (paresis) of the proximal parts of the

upper limbs, which is often unilateral and transient.

The symptoms associated with the development of

“hard disc” are characterized by headache and armache,

which are often symmetrical and accompanied by

transient localized palpatory tenderness at the level of

e-mail: [email protected]© Group of authors, 2016

doi: 10.17116/engneiro201680613-20

The First Experience with a New Technique of Portal Endoscopic Discectomy for Herniated Cervical DiscsA.O. GUSHCHA, S.O. ARESTOV, A.V. VERSHININ

Research Center of Neurology, Moscow, Russia

Selection of the most appropriate tactics for surgical treatment of herniated cervical discs is a topical issue to be discussed. The idea of herniated disc removal using an endoscopic technique is not new. This is a routine surgery for the lumbar spine. However, application of endoscopic techniques in the cervical spine surgery was first reported only in 2014 (J. Yang, et al.).Objective. This study was aimed at mastering the methodology of a new technique, portal endoscopic discectomy, determining the indications for this surgery for herniated cervical discs, and comparing outcomes of this surgery with outcomes of anterior microsurgical discectomy. Material and methods. The study included 25 patients, who underwent portal endoscopic cervical discectomy. A comparison group consisted of 25 patients, who underwent anterior microsurgical discectomy and placement of an interbody cage.Results. Comparison of surgical outcomes showed no significant difference (p>0.05) in the severity of postoperative local and radicular pain syndrome. According to the Neck Disability Index (NDI), significant improvement occurred in patients with endoscopic surgery. According to the Odom criterion, significant advantage in the number of excellent and good outcomes was observed in study group patients. There were significant differences between the groups in the duration of postoperative hospital stay. The average duration was 3 days in the study group and 5 days in the control group.Conclusion. Portal endoscopic discectomy is a highly effective treatment for herniated cervical discs, which provides clinical outcomes associated with much less surgical trauma. The study demonstrates not only the efficacy of the suggested technique, but also its safety compared to conventional anterior microsurgical techniques, which usually involve interbody fusion. This surgery is superior to other interventions in terms of the rate of rehabilitation and social adaptation of patients and reduces postoperative hospital stay.

Keywords: portal endoscopic discectomy, cervical disc herniation, endoscopic spinal surgery.


ORIGINAL ARTICLES

hernia, which has a certain diagnostic value. This variant

of the disease is characterized by multiple areas of

desensitization up to conduction anesthesia, originating

at the level of the lesion and accompanied by impaired

muscle strength below the segment concerned, sometimes

up to deep paresis. Clinical presentation of calcified

compressing structures in the cervical spinal canal is

characterized by normoreflexia or hyperreflexia, which is

most likely due to chronic circulatory disturbances in the

anterior spinal artery system.

In patients with “hard disc”, development of clinical

symptoms takes much more time compared to those in

with “soft” hernias.

Conventional CT and MPT-studies provide

complementary information in the diagnosis of the

disease. The former method is preferable to identify

compression factors (hernia, osteophytes), and the latter

is preferable to detect the results of compression

(compression of the spinal cord and roots). Bischoff

(2003) investigated sensitivity, specificity, and accuracy

of CT, MRI, and myelography when establishing the

“herniated disc” and “spinal stenosis” diagnoses. The

accuracy and sensitivity of CT is slightly higher compared

to MRI. CT remains the best method to assess central

stenosis. MRI provides images of the whole cervical spine

and enables detecting stenosis in frontal and sagittal

projections (Fig. 1).

The studies of J. Wilmink [6] showed the following

clinical and radiographic correlations of CT results.

1. Complete occlusion of the intervertebral

foramen by laterally migrated masses of the degenerated

intervertebral disc (“soft disc”) is always accompanied by

radicular syndrome.

2. Narrowing of the intervertebral foramen due to

osteophyte (“hard disc”) results in the root swelling and

less pronounced radicular syndrome compared to the first

variant.

3. Paramedian disc protrusion that does not result

in complete occlusion of the intervertebral foramen and

pronounced compression of the spinal cord often causes

the development of radicular symptoms on the

contralateral (with respect to hernia) side.

Treatment of compression syndromes caused by

degenerative changes in the cervical spine has a 50-year-

long history, and, despite this fact, there is currently no

common viewpoint on the criteria for selection of certain

surgical procedures. This can be explained, on the one

hand, by continuous improvement of the techniques of

cervical spine surgery and development of “spinal design”

operations, and, on the other hand, deepening of

understanding of the pathogenesis and biomechanics of

these changes. Both anterior and posterior approaches in

the cervical spine surgery have been developing in parallel

over 50 years. Many surgeons developed the anterior

approach through the interfascial space, using the

transverse or oblique incision along the anterior margin of

the sternocleidomastoid muscle [7, 8]. The history of

Fig. 1. Neurodiagnostic studies in patients with right-sided osteophyte at C5—C6 level on the right and “soft” disc hernia at C6—C7 level on the right. The use of CT (a) in combination with MRI (b, c) enabled determining the morphological character of root compression. The arrow shows the bone-density disc herniation.

a

b

c


Material and Methods

We compared surgical outcomes in 25 patients with

C5—C6 [9] and C6—C7 lateral disc herniation [16], who

underwent endoscopic portal cervical discectomy.

Retrospective evaluation of surgical outcomes in 25

patients, who were also operated on by the first author and

underwent a microsurgical single-level anterior cervical

discectomy with interbody fusion at C5—C6 or C6—C7,

was used as a comparison group. The operation performed

in the control group patients is described in detail in

relevant guidelines [14, 15].

In both groups, early postoperative outcomes were

assessed as follows: VAS (visual analogue scale) — timing

and extent of radicular pain regression; decrease in pain

based on NDI (Neck Disability Index) — social adaptation

of patients; Odom criteria — overall postoperative

recovery. NDI provides a measure of patient's social

adaptation based on summation of points characterizing

the possibility of usual activities (walking, sleeping,

reading, recreation, etc.). Odom characterizes the effect

of the surgery in general, from good to unsatisfactory.

Evaluation of NDI and Odom criteria was carried out

immediately before the discharge. In addition, the time of

postoperative hospital stay was evaluated.

Mann-Whitney test was used in statistical processing

to assess the validity of the results.

The technique of portal endoscopic cervical discectomy

Patient’s positioning on the operating table

The patient is laid on the operating table in prone

position with hands placed along the body. The head is

placed on the soft headrest or fixed in Mayfield head

clamp. The cervical spine is placed in neutral position.

Planning the incision

Electron-optical converter (EOC) is typically used

for incision planning, images of the cervical spine are

taken in the lateral projection. A sterile needle is placed in

the plane of the target intervertebral disc. Incision is

planned 1—2 cm lateral to the midline, depending on

patient’s physique (Fig. 2).

Operative approach

Skin incision is followed by incision of fascia and

EOC-controlled punctural placement of surgical cone at

the projection of the desired interval (Fig. 3). The base of

the lower articular process of the overlying vertebra is and

optimal point to place a port. Surgical port installation is

followed by preserving resection of adjacent vertebral

arches and flaval ligament is released. When the port is

properly installed, no significant resection of the

intervertebral joint is required. It should be remembered

that, according to various authors [16—18], resection of

posterior approaches begins in 1955, when

D. Northfield [9] proposed bilateral laminectomy,

extended by one segment above and below the pathological

level. In 1961, W. Scoville [10] performed the limited

bilateral laminectomy supplemented with bilateral facet

resection. The development of the posterior approached

was aimed at decompression of neural structures by means

of resection of the posterior supporting complex of the

arch and spinous process. These approaches did not

always enables removal of compressing masses located on

the ventral surface of the spinal canal, although several

cases of removal of disc hernia and vertebral body

osteophytes have been reported [11]. Posterolateral

approaches include posterior foraminotomy or

facetectomy. This surgical technique was developed in

1944 by R. Spurling [4] and later on, in more detail, by

Frykholm, W. Scoville [12] (“keyhole” technique). This

posterior approach enabled foraminotomy and herniated

disc resection through a small incision. However, most

neurosurgeons still prefer to use a more safe anterior

approach due to the probability of neurological deficit

and the need for segment stabilization [13]. Existing

endoscopic methods belong to intradisc interventions,

which are not capable of sufficient decompression of the

spinal structures.

During the last 10 years, portal endoscopic

discectomy, which was proved to be effective and safe,

has been widely used in our department to treat herniated

lumbar intervertebral discs [14]. Since 2014, this

technique has been successfully used to treat herniated

cervical intervertebral discs. In this paper, we provide a

detailed description of the portal endoscopic discectomy

for herniated cervical intervertebral discs and the most

important technical features of this method based on our

own experience.

It should be noted that this is the first ever detailed

report on application of this method in cervical surgery

both in Russian and international literature. When

analyzing published data, we found a large number of

research dealing only with application of full endoscopic

technique (i.e., cervical surgery through percutaneous

approach, both anterior and posterior, including only

foraminotomy) [15—17]. It should be taken into account

that both lumbar and cervical portal endoscopic methods

are technically similar to microsurgical interventions, but

differ from the latter in the degree of soft tissue

traumatization associated with these approaches and

visualization quality, which in this case enables “peeking

behind the root”.

The study was aimed at mastering the methodology of

the new technique, portal endoscopic discectomy,

determining the indications for this operation in patients

with herniated cervical disc, and comparing the results of

this operation with the results of the anterior microsurgical

discectomy.


ORIGINAL ARTICLES

25 to 50% of the intervertebral joint results in segmental

instability. Soft tissue removal from the intralaminar

space is followed by opening of the flaval ligament,

preferably as medial as possible and by blunt

dissection [19].

The main stage of the surgery

Opening of the flaval ligament usually results in

visualization of dural sac, whose separation provides the

approach to the gaine radiculaire. There is usually venous

plexus along the latter (see Fig. 3a), which is coagulated

and intersected. After that, the root becomes more mobile

despite the compression. Root displacement enables

visualization of disc hernia and its removal (see. Fig. 3b).

Surgical wound closure

The wound is closed layer by layer. Particular

attention is paid to restoration of the integrity of the

muscle aponeuroses in the surgical area.

Rigid cervical collar should be used for 3 weeks in the

early postoperative period to reduce axial loads on the

operated spinal motion segment.

Results

There was no worsening of neurological deficit in

both the study and control groups. In 2 (8%) patients in

the group of endoscopic removal of disc hernia, transient

numbness in the region of innervated dermatome was

observed followed by full regression by the time of

discharge. Preoperatively, median intensity of pain in the

shoulder and forearm as assessed by VAS score was 6 (3;

8) in the endoscopic discectomy group and 6 (4; 8) in the

microsurgical anterior discectomy group. After surgery,

this value decreased to 1 (0, 6) in the posterior endoscopic

discectomy group and 2 (1; 6) in the microsurgical

anterior discectomy group. In both groups, there was

significant decrease in pain (p=0.016 and p=0.034,

respectively). Immediately before discharge from the

Fig. 2. Positioning of incision, frontal (a) and lateral (b) projection (EOC display view).

a b

a b

Fig. 3. The main stage of the operation. a — separation of the gaine radiculaire; b — removal of disc herniation.


hospital, the level of pain in the shoulder and forearm did

not differ significantly in these two groups (p>0.05). When

assessing pain in the neck, two groups were comparable in

the preoperative period (p>0.05) and significant decrease

in the severity of pain was observed in the postoperative

period (p=0.024 in the study group and p=0.034 in the

control group) (Table 1).

All study group patients noted complete or nearly

complete regression of pain syndrome immediately after

the operation.

Significant improvement of the score was observed in

patients who underwent endoscopic surgery. In both

groups, patients were subjectively satisfied with the

outcome. As for Odom criteria, there were significantly

more excellent and good outcomes in study group patients

(Table. 2).

Significant differences were found, when comparing

the time of postoperative hospital stay: it was 3 (2; 5) days

in the study group and 5 (4; 6) days in the control group.

In the study group, 1 (4%) patient reported the recurrence

of radicular pain one week after surgery. Preoperative and

postoperative MPT of this patient are shown in Fig. 4

and 5. Control MRI showed that disс hernia was

completely removed and the pain was not associated with

its recurrence. Antineuritic therapy for 2 weeks resulted in

complete regression of pain syndrome.

Thus, these studies demonstrate safety and efficacy of

the posterior portal endoscopic discectomy. When the

anatomy of the compressing factor is quite clearly

understood, this type of intervention is superior to other

operations in terms of the rate of rehabilitation and social

adaptation of patients and shortens postoperative hospital

stay.

Our results provided the basis for formulation of

indications and contraindications for the portal cervical

endoscopic discectomy.

Surgery is indicated in the following cases:

— clinical presentation of radiculopathy

corresponds to the side and level of the lesion detected by

MRI/CT;

— CT/MRI studies confirm the correspondence

between the “soft” compression of the root, which is

located in the lateral third of the width of the spinal canal,

and the clinical presentation of the disease;

— there is no effect of conservative treatment

during 3 weeks.

The operation is contraindicated in the following cases:

— There are signs of segmental instability;

— There is kyphotic deformity of the spine at the

level of disc herniation.

Discussion

The choice of surgical approaches in the treatment of

compression syndromes presenting with neurological and

vascular disorders is associated with a number of

controversial issues [20, 21], although these interventions

have been existing for rather long period [15]. The main

problem is, which decompression option should be

selected, either anterior or posterior one. Both methods

enable quite adequate solution of this problem. Selection

of decompression direction is determined by localization

Table 1. The intensity of pain in the neck, shoulder, and forearm on the visual analogue scale (VAS) before and after surgery

CriterionPatients with endoscopic posterior discectomy

(n=25), study group

Patients with microsurgical anterior discectomy

(n=25), control group

Pain in the shoulder and forearm (median and range)

Preoperative score 6 (3; 8) 6 (4; 8)

Score before discharge 1 (0; 4) 2 (1; 6)

Whitney-Mann test, р 0,016 0,034

Pain in the neck (median and range)




Table 2. Surgical outcomes according to NDI index and Odom criterion

Criterion (criterion)Patients with endoscopic posterior

discectomy (n=25), study group

Patients with microsurgical anterior discectomy

(n=25), control group

NDI (median and range)




Odom criterion (median and range)

Very good/good 21 17

Satisfactory/unsatisfactory 4 8


ORIGINAL ARTICLES

a b

Fig. 4. Preoperative MRI.a — sagittal projection; b — axial projection (explanation in the text).

ba

Fig. 5. Postoperative MRI. a — sagittal projection; b — axial projection (explanation in the text).

Fig. 6. The algorithm of selection of surgical approach in patients with cervical spondylogenic compression.


of compressing factor as proved for single-level

procedures.

According to opinion of H. Jho expressed in a private

conversation, posterior cervical foraminotomy has

limitations in the case of frontal compression with

osteophyte, posterior compression with uncovertebral

joint, and pronounced cicatricial process. The cardinal

clinical syndrome of cervical radiculopathy requires more

thorough examination of the patient, since it is often not

accompanied by unequivocal x-ray data about the cause

of the compression, and almost never has pathognomonic

changes in neurovascular structures. The highest accuracy

of detection of muscular atrophy in corresponding

muscles was proved to be the main criterion of the level of

radiculopathy. Modern neurovisualization methods

enable identification of the compressing factor: “soft”

(herniated disc) or “hard” (osteophyte or bone spike),

which is a decisive factor in the choice of surgical

approach. In the case of lateral “soft” disc, posterior

portal endoscopic resection is indicated, whereas more

radical removal of osteophyte in this area can be achieved

through the ventral approach. The nature of the

compressing factor in patients with the cervical

radiculopathy syndrome should also be considered in the

context of neurological symptoms. In the case of

osteophyte, the severity of radicular symptoms (especially

pain) is substantially lower than in the case of “soft”

hernia.

To our knowledge, inefficiency of surgical treatment

of patients with radiculopathy is primarily due to

underestimation of neurological symptoms and

interpretation of neurovisualization data. In particular,

the paramedian location of disc hernia is often

accompanied by radicular symptoms in the contralateral

hand. The ignorance of this fact may cause inadequate

choice of the side of surgical approach and therefore the

lack of clinical effect of the surgery.

Confirmed spine deformity and detected segmental

instability are significant factors in choosing the direction

of surgical approach. Cervical spine kyphosis associated

with degenerative processes in the vertebrae always

suggests the use of ventral approach accompanied by

appropriate stabilizing measures.

Based on these data and surgical outcomes, we

developed the algorithm for selection of surgical approach

in patients with cervical spondylogenic compression

(Fig. 6).

The use of endoscopic microdiscectomy in the

treatment of herniated cervical intervertebral discs is

highly effective and provides clinical results with

considerably less surgical trauma. We discovered technical

features and proposed recommendations, which will

contribute to widespread use of this promising minimally

invasive technique in neurosurgical practice.


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ORIGINAL ARTICLES

disc herniation? A comparative cohort study. Spine (Phila Pa 1976). 2014

Oct 1;39(21):1743-1750.

PMID: 25010095

doi: 10.1097/BRS.0000000000000508

21. Li XC, Zhong CF, Deng GB, Liang RW, Huang CM. Full-Endoscopic

Procedures Versus Traditional Discectomy Surgery for Discectomy: A Sys-

tematic Review and Meta-analysis of Current Global Clinical Trials. Pain Physician. 2016 Mar;19(3):103-118.

PMID: 27008284

The article provides a detailed description and comparative

analysis of the use of innovative technique of portal endoscopic

discectomy in treatment of herniated cervical discs. The study

included 25 patients, who were operated on in 2014—2016. The

control group included 25 patients, who were operated on using

anterior cervical discectomy with installation of a single-level

interbody implant. The authors suggested indications for the

use of portal endoscopic discectomy: paramedian or lateral

herniation of the cervical disc with monoradicular symptoms

and no calcification of disc herniation as evidenced by CT. The

signs of segmental instability and spinal deformity, which is

usually indicative of segment stabilization, are considered as

contraindication. The technique of surgical intervention from

patient positioning on the operating table to surgical wound

suturing is described in detail.

Treatment outcomes were assessed on VAS scale (visual

analog scale), preoperative and postoperative values were

compared. Preoperative comparison of the groups showed no

statistically significant difference between the groups of

patients. Social adaptation and quality of life have been assessed

using NDI (Neck Disability Index). Additionally, overall

recovery of patients was compared using Odom criterion and

time of patients’ hospital stay was evaluated. High level

statistical processing of the results was performed using modern

statistical processing tools, which proves the validity of the

results of the study.

In my opinion, this article is a valuable and relevant

scientific work. The provided information can be used to

develop methods of portal cervical endoscopic discectomy. The

presented data demonstrate the efficacy and safety of the

method.

Commentary

The bulk of the article focuses on describing the techniques

and nuances of the operation. In our clinic, we use portal

endoscopic discectomy to treat lumbosacral intervertebral disc

herniation, but the use of this technique in the cervical spine is

associated with a number of difficulties. The correct positioning

of the endoscopic port is the most challenging problem. The

authors carefully describe this issue and note the nuances, so

that it is, in fact, guidelines to master this method.

Selection of patients for this operation is a disputable

question. Indeed, the posterior approach is only suitable for

resection of lateral and paramedian disc hernia, since even a

small traction of the compressed spinal cord can cause severe

postoperative neurological disorders. This fact was the main

argument to switch from the posterior microsurgical approach

to anterior approaches in the late 1900s. The authors

supplemented the standard preoperative examination complex

with CT of the cervical spine to measure preoperative density of

disc hernia. This is due to the fact that significant traction of

nerve structures and the use of bulky microsurgical instruments

is required for removal of ossified herniation of intervertebral

discs, which in turn eliminates the advantages of endoscopic

approach. In our view, this additional preoperative examination

is reasonable and improves safety of the technique.

Therefore, this material is relevant and highly informative.

The detailed description of the procedures and techniques of

the portal endoscopic discectomy makes this work a valuable

guideline for the operation. This technique is a new promising

trend in neurosurgery. The authors fully proved the effectiveness

and safety of the method.

N.L. Konovalov (Moscow)

18. Zdeblick TA, Ducker TB. The use of freeze-dried allograft bone for anterior

cervical fusions. Spine (Phila Pa 1976). 1991 Jul;16(7):726-729.

PMID: 1925745

19. Goushcha AO, Arestov SO. Torakoskopicheskaya khirurgiya v lechenii

novoobrazovanii pozvonochnika i paraspinal'nykh neirogennykh

opukholei. Russian traumotology and orthopedy. 2010;2(56):129-131.

(In Russ.).

20. Yang JS, Chu L Chen L, Chen F, Ke ZY, Deng ZL. Anterior or posterior

approach of full-endoscopic cervical discectomy for cervical intervertebral



doi: 10.17116/engneiro201680621-31

Clinical and Morphological Characteristics, Diagnostic Criteria, and Outcomes of Surgical Treatment of TSH-secreting Pituitary AdenomasL.I. ASTAF’EVA1, B.A. KADASHEV1, L.V. SHISHKINA1, P.L. KALININ1, D.V. FOMICHEV1, M.A. KUTIN1, I.A. AREF’EVA1, L.K. DZERANOVA2, YU.G. SIDNEVA1, I.S. KLOCHKOVA1, D.L. ROTIN3

1Burdenko Neurosurgical Institute, Moscow, Russia; 2Endocrinology Research Center, Moscow, Russia; 3Moscow Scientific Clinical Center, Moscow, Russia

Thyrotropinomas (TSH-secreting tumors) are a rare type of pituitary adenomas, which account for about 0.5—2.0% of all pituitary tumors. The criterion of thyrotropinoma includes visualization of the tumor along with normal or elevated blood level of the thyroid-stimulating hormone (TSH) and high level of free T4 (fT4) and free T3 (fT3).Objective. The study was aimed at investigating clinical, diagnostic, and morphological characteristics and treatment outcomes of TSH-secreting pituitary tumors.Material and methods. The study included 21 patients aged 15 to 67 years with pituitary adenoma and normal or elevated blood level of TSH in combination with elevated levels of fT4 and fT3, who were operated on at the Burdenko Neurosurgical Institute in the period between 2002 and 2015. The patients were tested for the levels of TSH, fT4, fT3, prolactin, cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol/testosterone, and insulin-like growth factor (IGF-1) before surgery, in the early postoperative period, and 6 months after surgery. The thyroid status was evaluated using the following reference values: TSH, 0.4—4.0 mIU/L; fT4, 11.5—22.7 pmol/L; fT3, 3.5—6.5 pmol/L. An immunohistochemical study of material was performed with antibodies to TSH, PRL, GH, ACTH, LH, FSH, and Ki-67 (MiB-1 clone); in 13 cases, we used tests with antibodies to type 2 and 5 somatostatin receptors and D2 subtype dopamine receptors.Results. Thyrotropinomas were detected in patients aged 15 to 67 years (median, 39 years) with an equal rate in males (48%) and females (52%). Before admission to the Neurosurgical Institute, 11 (52%) patients were misdiagnosed with primary hyperthyroidism; based on the diagnosis, 7 of these patients underwent thyroid surgery and/or received thyrostatics (4 cases). Hyperthyroidism symptoms were observed in 16 (76%) patients. The blood level of TSH was 2.47—38.4 mIU/L (median, 6.56); fT4, 22.8—54.8 nmol/L (median, 36); fT3, 4.24—12.9 pmol/L (median, 9.66). Tumors were endosellar in 4 (19%) cases and the endo-extrasellar in 17 (91%) cases. Total tumor resection was performed in 7 (33%) patients. All these tumors were either endosellar or endo-suprasellar. No total resection was performed in patients with infiltrative growth of adenoma (invading the skull base structures). An immunohistochemical study of resected tumor specimens detected only TSH expression in 3 (14%) cases; 18 (86%) tumors were plurihormonal and secreted TSH and GH and/or PRL. Of 13 tumors, expression of the type 2 dopamine receptor was detected in 9 (69%) cases; expression of type 5 and type 2 somatostatin receptors was found in 6 (46%) and 2 (15%) cases, respectively.Conclusion. Postoperative decrease in the TSH level to 0.1 mIU/L or less was the criterion of total tumor resection. Total resection was performed in 33% of patients, having only endosellar and endo-suprasellar tumors. In most cases, tumors were plurihormonal and secreted TSH and GH and/or PRL.

Keywords: thyrotropinoma, TSH-secreting pituitary adenoma, central hyperthyroidism, acromegaly, somatostatin analogues.

Abbreviations:ACTH — adrenocorticotrophic hormone

AB — antibodies

IMH — immunohistochemical study

IGF-1 — insulin-like growth factor-1

LH — luteinizing hormone

OGTT — oral glucose tolerance test

PRL — prolactin

fT3 — free T3

fT4 — free T4

STH — somatotropic hormone

TRH — thyrotropin-releasing hormone

TSH — thyroid stimulating hormone, thyrotropic hormone

TSH-PA — TSH-secreting pituitary adenoma

FSH — follicle stimulating hormone

CAIT — chronic autoimmune thyroiditis

D2DR — D2 subtype dopamine receptors

L-T4 — levothyroxine

SSt2 — type 2 somatostatin receptors

SSt5 — type 5 somatostatin receptors


ORIGINAL ARTICLES

Thyrotropinomas (TSH-secreting tumors) are a rare

type of pituitary adenomas, which account for about

0.5—2.0% of all pituitary tumors. The criterion of

thyrotropinoma includes visualization of the tumor along

with normal or elevated blood level of the thyroid-

stimulating hormone (TSH) and high level of free T4

(fT4) and free T3 (fT3). Overproduction of TSH by these

tumors leads to hyperstimulation of the thyroid gland

and clinical presentation of so-called central

hyperthyroidism. This TSH production is autonomous

due to impaired down-regulation of thyroid hormones,

which affects the hypothalamic-pituitary-thyroidal

system. Low incidence of these tumors as well as

sometimes insufficient doctors’ awareness of clinical

features and diagnosis of central hyperthyroidism can

lead to hyperdiagnosis of Basedow's disease or other

thyroid diseases involving hyperthyroidism, which can

result in unreasonable thyroid surgery and/or therapy

with radioactive iodine.

Material and methods

The study included patients with pituitary adenoma

and normal or elevated blood level of TSH in combination

with elevated levels of fT3 and fT4, who were operated on

at the Burdenko Neurosurgical Institute during the

period from 2002 to 2015. The group included 21 patients

aged 15 to 67 years (median 39 years), 11 females (52%)

aged 15 to 63 years (median 30 years) and 10 males (48%)

aged 15 to 67 years (median 49 years).

All patients underwent MRI of the brain. All

identified tumors were macroadenomas sized 16 to 64

mm in diameter (median 26 mm). We classifies them

according to their growth pattern and location (see Table). Thus, endo-sellar and endo-suprasellar adenomas

not invading skull base structures (10 cases) were

considered as non-infiltrative. Endo-extrasellar tumors

invading the skull base structures, including cavernous

sinus, were considered as infiltrative (11 cases).

The patients were tested for the levels of TSH, fT4,

fT3, prolactin, cortisol, LH, FSH, estradiol/testosterone,

and, in 13 cases, IGF-1 before surgery and in the early

postoperative period. In the case of high level of IGF-1,

growth hormone level was additionally studies during

oral glucose tolerance test. Thyroid status was evaluated

using the following reference values: TSH, 0.4—4.0

mIU/L; fT4, 11.5—22.7 pmol/L; fT3, 3.5—6.5 pmol/L.

At admission to the Burdenko Neurosurgical Institute,

thyroid status of patients who had a history of

thyroidectomy and patients treated with somatostatin

analogues or thyrostatics was assessed prior to the

thyroidectomy or beginning of medication. In patients

with thyrotropinoma and primary hypothyroidism,

evaluation was carried out during therapy with

levothyroxine; high levels of free thyroid hormone

fractions and high levels of TSH were the criteria for

inclusion in the study.

The patients were operated on through the

transsphenoidal approach in 18 cases, including 14 cases

of endoscopic endonasal approach and 3cases of

transcranial approach (cases 2, 8, and 9). One patient

(case 9) was reoperated at the Burdenko Neurosurgical

Institute for continued tumor growth after non-radical

transcranial tumor resection 6 years before reoperation.

Another patient (case 19) was previously operated on in

other clinic and was admitted with tumor recurrence 18

months after surgery. In both cases, hormone level before

the first operation is unknown.

Operating material was stained with hematoxylin

and eosin using the standard procedure followed by

thorough histological examination.

Immunohistochemical study of the material was carried

out using antibodies (ABs) to TSH, PRL, STH, ACTH,

LH, FSH, and Ki-67 proliferation marker (MiB-1

clone). Tumors with Ki-67 MI expression of less than 3%

were considered as non-aggressive, 3% or more —

aggressive. In 13 cases, AT tests were carried out with

type 2 and 5 somatostatin receptors and D2 subtypes

dopamine receptors (D2DR).

Follow-up study was carried out in 12 patients.

Follow-up time was 1 month to 7 years (median, 6

months).

Results

Clinical presentation of the disease included mainly

symptoms of hyperthyroidism in 16 (76%) of patients,

whose history was 1 to 13 years (median 4 years).

Furthermore, we detected symptoms of mass effect of the

tumor: visual impairment in 8 (38%) patients and

cephalgic syndrome in 7 (33%). Two patients were

admitted in grave condition with large tumors

accompanied by occlusive symptoms due to compression

of the third ventricle (case 2, 8).

Four of eight reproductive-age females had

amenorrhea (in two of them it was primary); 4 female

patients had normal menstrual function. Lactorrhea was

observed in 3 females. Androgen deficiency was

diagnosed in 3 males.

Psychopathology usually fit into the presentation of

anxiety and phobic disorders in the form of neurotic

syndrome (12 patients) and panic attacks (11). Emotional

disturbances in the form of depression were observed

only in 3 patients. Eight patients complained of fatigue

and weakness, 8 — palpitations, 5 — anxiety, 11 — mood

lability, 3 — sleep disorder, 3 — sweating, 3 — tremor, 2

— subfebrile temperature, 2 — weight loss. The patients

often had a combination of the aforementioned

complaints. Psychiatric symptoms were most often

moderate (13 patients).

Seven patients (see Table) had a history of thyroid

surgery (6 — hemithyroidectomy, one of these patients

had been operated on twice; 1 — thyroidectomy).


Four patients received thyreostatic therapy; at the

time of admission, 2 of them (cases 9 and 10) still received

thyrostatics. In these patients, fT4 levels before treatment

with thyrostatics were 27.4 and 54.8 nmol/L and TSH

levels were 5.59 and 6.52 mIU/L, respectively. At the

time of admission to the Burdenko Neurosurgical

Institute, normalization of fT4 level to 17.5 and 22.0

nmol/L was accompanied by increase in TSH levels to

9.72 and 10.2 mIU/L, respectively.

Thyroid ultrasound was performed in 13 patients:

diffuse goiter was detected in 4 patients, nodular goiter —

3, diffuse nodular goiter — 1, and thyroid hypoplasia was

observed in 1 patient with secondary TSH-PA.

At admission, three patients received levothyroxine:

one of them previously underwent thyroidectomy (case

8), two patients with chronic autoimmune thyroiditis

(CAIT) had primary hypothyroidism. Despite the high

dose of levothyroxine (200 and 175 μg) and high level of

free fractions of the thyroid hormones, TSH level was

high (cases 16 and 19). We regarded these tumors as

secondary thyrotropinomas. One of them had previously

been operated on at the other hospital and was admitted

to the Burdenko Neurosurgical Institute with recurrent

pituitary adenoma.

Three patients had symptoms of acromegaly (change

in appearance, growth of extremities, etc), confirmed by

the results of hormonal blood test (high levels of IGF-1

and absence of STH suppression below 1.0 ng/ml during

the oral glucose tolerance test, OGTT).

In patients with TSH-PA, blood level of TSH was

2.47—38.4 mIU/L (median, 6.56), fT4 level — 22.8—

54.8 nmol/L (median, 36), fT4 level — 4.24—12.9

pmol/L (median, 9.66).

We found no correlation between the levels of TSH

and fT4 (Fig. 1), between the level of TSH and fT3, as

well as fT4 and fT3.

IGF-1 was tested in 10 patients with no clinical

symptoms of acromegaly, 2 of them had elevated levels of

IGF-1. They were tested for STH during OGTT,

suppression of STH below 1.0 ng/ml was found. Five

(24%) patients had hyperprolactinemia from 528 to 2678

mIU/L (median, 758).

Two patients (one with TSH-PA and the other with

mixed TSH-STH-secreting adenoma) were

preoperatively treated with prolonged somatostatin

analogues, which resulted in normalization of TSH,

STH, and IGF-1 levels (cases 12 and 14).

All 21 patients had macroadenomas: 4 cases —

endosellar, 6 cases — endo-suprasellar, not invading the

skull base structures (non-infiltrative). In 11 patients,

tumors invaded the skull base structures, including the

cavernous sinus (infiltrative). When comparing the

growth pattern of tumors in 7 patients having a history of

thyroid surgery, we found that, in this group, infiltrative

growth occurred in 5 (71%) cases, whereas in 14 patients,

who had no previous thyroid surgery, infiltrative growth

occurred in 6 (43%) cases. However, there were no

statistical differences, when comparing tumor growth

pattern in the groups of patients with and without history

of thyroid surgery, as well as in various age and gender

groups.

Postoperative TSH level was elevated in only 1 out of

21 patients. It decreased in 20 patients; in 10 cases, it was

even lower than normal (0.01 ± 0.19 mIU/L), and in 10

patients it reached the normal range (0.68—2.9 mIU/L).

Maximal reduction occurred on day 1 after operation.

The rate of decrease in fT4 levels were significantly lower.

Thus, fT4 level tested on day 1—3 after surgery remained

high in all patients. However, subsequent measurements

on day 5—7 days after surgery showed its normalization

or reduction in most of the cases.

The tumor was totally resected only in patients with

endosellar (3 cases) and endo-suprasellar (4) tumors. In

the case of infiltrative tumor, there were no cases of total

resection. We studies protocols of operations and

concluded that thyrotropinomas were in most cases

similar to other typical adenomas, they were rarely dense

and well perfused. Intense venous bleeding occurred only

in 2 cases during tumor resection from the cavernous

sinus. Close adherence of the tumor with vessels and

nerves was observed in 2 cases during transcranial

operations. One patient had a large hemorrhagic cyst

within the tumor.

We compared postoperative TSH levels in patients

with radical and non-radical tumor resection. In the first

case, TSH level measured in the early postoperative

period was not detectable or no more than 0.1 mIU/L.

Normalization of TSH or its reduction to 0.1 mIU/L,

as well as transient postoperative hypothyroidism, are

not the criteria of completeness of tumor resection. Thus,

normalization or reduction of serum level of TSH, fT4,

and fT3 was observed in all patients even in the case of

subtotal resection. However, further follow up of 5

patients with postoperative euthyroidism and tumors

remnants showed that 4 patients had elevated levels of

TSH and/or fT4 6—12 months after surgery; one patient

with mixed STH-TSH-secreting tumor maintained

euthyroidism, but the levels of STH and IGF-1 remained

high. These patients underwent stereotactic radiotherapy

of residual tumor tissue.

Fig. 2 shows the dynamics of TSH and fT4 in

patient A., 21 years old, with non-radical tumor resection,

Fig. 3 shows changes in the level of TSH and fT4 in

patient B., 38 years old, with radical tumor resection.

As can be seen from Fig. 2, subtotal tumor resection

in patient A. led to decrease in TSH level to 0.52 mIU/L

on day 1 after the operation and development of transient

hypothyroidism. However, euthyroid state was diagnosed

in 1 month, and recurrence of hyperthyroidism occurred

in 1 year. The patient underwent a course of stereotactic

radiation therapy followed by remission of the disease.

TSH level below 0.1 mIU/L was considered as the

criterion of radical tumor resection.


ORIGINAL ARTICLESSu

mm

ary

tabl

e of

the

mai

n da

ta o

f 21

patie

nts

with

thyr

otro

pino

ma

Pri

or

to a

den

om

ec

tom

y a

nd

tre

atm

en

t w

ith

th

yro

sta

tic

s a

nd

/or

SA

in

th

e e

arl

y

po

sto

pera

tive p

eri

od

an

d i

n 6

—1

8 m

on

ths

Aft

er

pit

uit

ary

ad

en

om

ec

tom

yIM

G c

ha

rac

teri

stic

s o

f re

sec

ted

tu

mo

rs*

S/N

S

ex

Age,

yea

rs

His

tory

of

trea

tmen

t

Th

yro

id

sta

tus

TS

H,

mIU

/L

fТ4

,

pm

ol/

L

PR

L,

mIU

/L

Tu

mo

r

gro

wth

pa

ttern

TS

H,

mIU

/L

fТ4

,

pm

ol/

l

MR

I si

gn

s o

f

tum

or

rem

nan

ts

Th

yro

id

sta

tus

Tre

atm

en

tT

SH

PR

LS

TH

DR

-D2

Sst

2S

st5

Ki-

67

,

%

1F

25

-H

yp

erT

2,7

14

3,1

72

66

Inf

0,1

92

0,6

0N

DN

D+

+

+

+

–+

0—

1

2F

15

-H

yp

erT

3,1

53

7,0

01

47

Inf

2,3

53

0,4

0Y

es

Hy

perT

RT

+

––

+–

–0

—1

3F

26

-H

yp

erT

4,0

53

1,7

08

50

No

n-

inf

<0

,01

11

,70

No

Hy

po

TL

-Т4

+

+

+

ND

ND

ND

2

4M

38

-H

yp

erT

4,2

82

3,6

04

20

No

n-

inf

0,0

62

8,3

0N

oH

yp

oT

L-Т

4+

+

+

N

DN

DN

D3

5M

67

-H

yp

erT

4,7

53

9,5

01

33

No

n-

inf

0,0

91

7,3

0N

oH

yp

oT

L-Т

4+

+

+

N

DN

DN

D3

6M

45

HM

EH

yp

erT

+A

CR

O

5,0

13

9,2

01

34

No

n-

inf

0,9

22

2,3

0N

DN

D+

+

+

N

DN

DN

D5

7F

30

-H

yp

erT

5,2

14

0,5

02

73

No

n-

inf

<0

,01

10

,40

No

Hy

po

TL

-Т4

+

+

+

ND

ND

ND

5

8M

39

-H

yp

erT

5,5

92

0,5

64

20

Inf

2,9

02

1,5

0N

DN

D+

−

−+

––

0—

1

9F

56

HM

E,

TS

Hy

perT

5,5

92

7,4

02

67

8In

f2

,40

21

,30

Yes

ND

+

+

+

+–

–0

—1

10

M2

1T

SH

yp

erT

6,5

25

4,8

02

37

Inf

0,5

23

3,1

1Y

es

Hy

perT

RT

+

−−

––

–0

—1

11

M3

4-

Hy

perT

6,5

63

6,4

05

28

Inf

2,1

32

1,5

0N

DN

D+

−

+

––

–0

—1

12

M6

5H

ME

,

SA

Hy

perT

7,5

02

6,9

02

80

Inf

1,1

21

1,8

0N

DN

D+

+

+

N

DN

DN

D0

—1

13

M5

9H

ME

Hy

perT

+A

CR

O

7,7

03

6,1

01

48

Inf

0,1

41

0,5

0Y

es

Eu

T+

AC

RO

SA

,RT

+

+

+

ND

ND

ND

5

14

M5

3S

AH

yp

erT

7,9

62

8,8

61

51

No

n-

inf

0,1

01

5,1

0N

oE

uT

No

+

+

+

+–

+2

15

F3

3-

Hy

perT

10

,87

39

,73

19

09

Inf

0,1

61

6,9

0N

DN

D+

+

+

+

–+

0—

1

16

F3

9-

Hy

po

T1

3,5

02

2,8

07

05

No

n-

inf

0,1

01

3,0

0N

oH

yp

oT

L-Т

4+

+

+

N

DN

DN

D3

17

F1

5-

Hy

perT

13

,96

23

,70

54

0N

on

-

inf

0,0

11

0,9

0N

oH

yp

oT

L-Т

4+

−

+

+–

+5

18

F6

3T

EH

yp

oT

22

,93

28

,30

75

8N

on

-

inf

1,4

49

,80

ND

ND

+

+

−–

–+

0—

1

19

F2

1-

Hy

po

T2

7,9

02

4,5

02

88

No

n-

inf

2,4

72

7,2

0N

oE

uT

L-Т

4+

+

−

+–

+5

20

F5

6H

ME

,

TS

Hy

perT

28

,10

36

,20

48

3In

f4

,20

24

,90

Yes

Hy

perT

RT

+

−+

+

+–

0—

1

21

F6

0H

ME

,

TS

Hy

perT

+A

CR

O

38

,40

52

,80

49

9In

f1

,60

24

,50

ND

ND

+

−+

–+

–0

—1

Not

e. H

ME

— h

em

ith

yro

idec

tom

y;

TE

— t

hy

roid

ec

tom

y;

TS

— t

hy

rost

ati

cs;

Hy

perT

— h

yp

ert

hy

roid

ism

; H

yp

oT

— h

yp

oth

yro

idis

m;

Eu

T e

uth

yro

id;

AC

RO

— a

cro

mega

ly,

the a

cti

ve p

ha

se;

Inf

— i

nfi

ltra

tive t

um

or;

No

n-i

nf

— n

on

-

infi

ltra

tive t

um

or;

ND

— n

o d

ata

; L

-T4

— l

evo

thy

rox

ine;

SA

— s

om

ato

sta

tin

an

alo

gu

es;

RT

— r

ad

ioth

era

py

. *

no

ca

ses

of

ex

pre

ssio

n o

f L

H,

FS

H,

AC

TH

were

dete

cte

d.


As can be seen from Fig. 3, radical tumor resection in

patient B. was accompanied by decrease in TSH level to

0.06 mIU/L on day 1 after surgery and persistent

hypothyrosis. Disease remission was observed throughout

the whole follow-up period (2 years). The patient was

administered with levothyroxine 1 month after surgery.

Four patients with radical tumor resection developed

panhypopituitarism, which persisted 6—18 months after

surgery (secondary hypothyroidism, hypocorticism,

hypogonadism, STH-deficiency); in 3 of them, it

occurred in combination with diabetes insipidus.

IMH-study of resected tumor samples showed that

all tumor were stained with AB to TSH; expression of

only TSH was detected in 3 (14%) cases (“pure” TSH-

secreting tumors), in 18 (86%) cases, tumors were

plurihormonal: 2 cases demonstrated expression of TSH

and PRL, 4 cases — TSH and STH, 12 cases — TSH,

STH, and PRL (Fig. 4).

In 4 (29%) out of 14 cases with expression of PRL,

there was increased blood level of PRL before surgery

(758 mIU/L, 850 mIU/L, 1909 mIU/L, 2678 mIU/L);

the remaining 10 (71%) tumors were accompanied by

normoprolactinemia (133—288 mIU/L). Tree (19%) out

of 16 patients with STH expression in tumor tissue were

diagnosed with acromegaly (see Table).

Expression of type 2 dopamine receptors (D2DR)

was detected in 9 (69%) of the 13 tumors, type 5

somatostatin receptor (SSt5) — 6 (46%), type 2

somatostatin receptor (SSt2) — 2 (15%) (see Table).

In 5 of 9 cases, D2DR expression occurred in

combination with expression of PRL. In 4 of 6 cases,

SSt5 expression was accompanied by STH expression.

Two tumors with SSt2 expression were also associated

with expression of STH, however, there were no cases of

adenoma with concomitant expression of SSt5 and SSt2.

The patients, who preoperatively received somatostatin

analogues with a positive effect in the form of

normalization of TSH and fT4 levels, demonstrated

expression of TSH and STH (case 12) and SSt5 (case 14)

in tumors.

There was no relationship between expression of

PRL and dopamine receptors, as well as STH and

somatostatin receptors in tumor cells.

The group average Ki-67 MI was 0—5% (median

1%), it was less than 3% in 13 cases, 3% or more in 8

cases. No statistical difference was found when analyzing

the proliferative activity of the pituitary tumor (Ki-67

MI) in patients who previously underwent thyroid

surgery and not operated patients (see Table).

Discussion

TSH-PA accounts for 0.5—2% of all pituitary

tumors [1]. The first case of hyperthyroidism and increase

in sella dimensions was described in 1960. [2]. In 1970, S.

Hamilton et al. [3] described TSH-PA with proved TSH

measurement using radioimmunoassay. Previously,

these tumors were considered casuistic and were detected

at the stage of large invasive pituitary macroadenomas.

However, the discovery of supersensitive hormonal

methods and high-resolution neuroimaging techniques

facilitated detection of TSH-PA at the stage of small

tumors. Recently published data show that the incidence

of TSH-PA in European countries may be 0.28 cases per

1 million population [4]. The incidence of TSH-PA is

equal in males and females, in contrast to the

predominance of females among the patients with thyroid

diseases [5]. Familial cases of TSH-PA were described

within MEN-1 [6] and in FIPA-families (familial

isolated pituitary adenoma associated with AIP gene

mutation) [7].

0

10

20

30

40

50

60

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

TSH

fT4

Levels of TSH, mIU/L and fT4, pmol/L

Casenumbers

Fig. 1. Preoperative blood level of TSH and fT4 in patients with thyrotropinoma. Dotted lines show the upper limits of reference values for both parameters. No correlation between blood levels of TSH and fT4 were found.


ORIGINAL ARTICLES

TSH-PA occurs in various age groups of patients

from 8 to 84 years [8—10]. However, most of the cases

described in the literature occurred in patients aged 50—

60 years [1]. In our study, the average age of males was 49

years, females were younger, their average age was 30

years.

The criteria of TSH-secreting pituitary tumors

include its visualization and normal or elevated blood

levels of TSH along with elevated levels of fT4 and fT3.

The symptoms of hyperthyroidism in combination with

these hormonal values exclude Graves disease [11]. In

difficult diagnostic cases, when there is no obvious

clinical hyperthyroidism and TSH-PA cannot be reliably

diagnosed based on the analysis of basal levels of

hormones, functional tests are used (test with thyrotropin-

releasing hormone, TSH), triiodothyronine suppression

assay, assessment of the molar ratio of α-subunit/TSH).

Differential diagnosis with the syndrome of thyroid

hormone resistance, which is also characterized by high

levels of fT4 and fT3 in combination with high or normal

level of TSH is the most challenging problem. This

syndrome is characterized by reduced sensitivity of

peripheral tissues to thyroid hormones; it is an autosomal

dominant hereditary disease caused by mutation in the

gene encoding β-type receptor to thyroid hormones [1,

12]. Pituitary adenoma detected by MPT-study in most

cases confirms TSH-PA. However, there are reported

cases of combination of the syndrome of thyroid hormone

resistance with TSH-secreting pituitary microadenomas

and pituitary incidentaloma [13].

According to the literature [14], normal level of TSH

is detected in approximately 30% of cases of TSH-PA.

Despite the TSH-dependent genesis of hyperthyroidism,

we found no direct correlation between the level of fT4

and TSH in our study. Similar data are reported in the

review by R. Beck-Peccoz [1].

Normal level TSH along with high levels of fT3 and

fT4 can be explained by increase in biological activity of

TSH molecule [15]. TSH molecules secreted by pituitary

tumors are heterogeneous and may have normal,

reduced, or increased ratio between their biological and

immunological activity, which that can be associated

with post-translation changes in the tumor cell [16, 17].

Normal blood level of TSH in some TSH-PA patients

justifies the need for testing both TSH and free fractions

of thyroid hormones in all patients with pituitary

adenoma.

6,52

0,52 0,68

2,79 2,94 2,17 3,16 2,48

1,73 1,56

Preopera�ve

1 day

5days

14days

1month

6months

1 year 2 years 3 years 4 years

TSH 4,0

0,4

0,1

Fig. 2. Patient A., 21 years old, with non-radical tumor resection (case 10). a — dynamics of TSH level; b — dynamics of fT4 level (yellow dotted line show upper and lower limits of reference values of blood level of TSH and fT4, respectively;

red dotted line shows the threshold, below which TSH values correspond to completeness of surgery).

54,8

33,1

10,1 7,18

18,9 22

27,3

19,4 14,2 12,4

fT4, pmol/L

fT4 22,7

11,5

Preopera�ve

1 day

5days

14days

1month

6months

1 year 2 years 3 years 4 years

b

a


Cases of TSH-secreting tumors associated with

chronic autoimmune thyroiditis have been reposted in

the literature [18—20]. Normal or elevated level of TSH

along with high level of fT4 and fT3 [18] is also considered

a diagnosis criterion of TSH-PA in patients with primary

hypothyroidism resulting from CAIT or thyroidectomy,

who receive replacement therapy with levothyroxine. We

reported 2 cases of TSH-PA in CAIT patients. Despite

the high dosed of levothyroxine and elevated level of fT4,

TSH level remained high. MRI study detected decrease

in tumor size in one case, and relapse after previous

pituitary adenomectomy in the other. Histological

examination confirmed the presence of mixed pituitary

adenoma with expression of TSH, PRL, and STH in

both cases. The role of long-lasting increase in TSH level

and pituitary hyperplasia in CAIT patients in the

pathogenesis of TSH-PA was discussed in the literature

[19, 20].

Clinical presentation of TSH-PA consists of

symptoms of hyperthyroidism and mass-tumor effect.

Symptoms of hyperthyroidism were detected in most

(76%) patients and were similar to manifestation of

primary hyperthyroidism, but they were characterized by

milder course and absence of other autoimmune

syndromes, which are common in diffuse toxic goiter

(endocrine ophthalmopathy, pretibial myxedema, and

acropathy). Prevalence of circulating antibodies to

thyreoglobulin and thyroid peroxidase in TSH-PA

patients is similar to that in the general population.

However, the literature [21, 22] described the patients

who developed Graves' disease after resection of pituitary

adenoma; bilateral exophthalmos in combination with

autoimmune thyroiditis. In most patients,

hyperstimulation of thyroid with TSH results in diffuse

increase in thyroid size, in 72% of cases — to formation

of single or multiple nodules [1]. Goiter is usually

detected even in patients who previously underwent

partial thyroidectomy due to growth of residual thyroid

tissue. Differentiated thyroid cancer was reported in

several patients with TSH-PA [23—26]. In patients with

thyroid nodules, monitoring of thyroid nodules and thin-

needle aspiration biopsy are required.

In most cases of TSH-PA reported in the literature,

where patients were first misdiagnosed with primary

4,28

0,06 0,01 0,01

0,16 0,27 0,68 0,7

Preopera�ve

1 day 5 days 1 month 2 months 6 months 1 year 2 years

TSH, mIU/L

TSH

L-Т4

0,4 0,1

4,0

23,6

28,3

16,9

7,00

12,6 12,6 13,2 13,5

Preopera�ve

1 day 5 days 1 month 2 months 6 months 1 year 2 years

fT4, pmol/L

fT4

L-T4

22,7

11,5

Fig. 3. Patient B., 38 years old, who underwent radical tumor resection (case 4). a — dynamics of TSH level; b — dynamics of fT4 level (yellow dotted line show upper and lower limits of the reference values of blood level of TSH and fT4,

respectively, red dotted line shows the threshold, below which TSH values correspond to completeness of surgery).

б

а


ORIGINAL ARTICLES

hyperthyroidism (Graves' disease), they often had a

history of thyroid surgery and/or radioactive iodine

therapy. In these cases, tumors often become more

aggressive and demonstrate infiltrative growth pattern.

Decrease in blood levels of circulating thyroid hormones

resulting from this treatment leads to activation of tumor

growth by a mechanism similar to development Nelson

syndrome after bilateral adrenalectomy during treatment

of Cushing's disease [1].

Likewise, more than half (52%) of patients in our

study were misdiagnosed with primary hyperthyroidism.

For this reason, most of them underwent thyroid surgery

and/or received thyreostatic therapy. In our study, we

found no clear statistical differences in the infiltrative

growth pattern depending on the previous thyroid

surgery. This is probably due to the general late diagnosis

of TSH-PA, when they are detected at the stage of large

tumor. Nevertheless, 7 patients were operated on at our

institution over the last 2 years (2014—2015), and only 3

(43%) of them had endosellar adenomas and

hyperthyroidism without symptoms of tumor mass effect,

whereas during the period from 2002 to 2013, most

patients, 13 (93%) of 14, had large tumors and were

diagnosed at the stage of tumor mass effect with

pronounced visual or other neurological disorders. It is

likely that in the future, given the use of ultra-sensitive

hormonal methods, as well as better doctors’ awareness

of these rare tumors, the rate of early detection of TSH-

PA at the stage of small-size tumor will increase.

Most of TSH-PA secret not only TSH, but also other

pituitary hormones, mainly STH and PRL. This may be

due to the fact that somatotropic, lactotropic, and

thyrotropic cells have a common progenitor cell. A rare

type of mixed TSH/gonadotropin secreting adenoma is

described in the literature without hypersecretion of

ACTH in the blood; the mechanism of occurrence of

these tumors have not been studied, because thyrotropic

and gonadotropic cells have different progenitor cells [1].

Clinically silent thyrotropinomas with TSH expression

but without increase in blood level of TSH and clinical

presentation of hyperthyroidism have been reported [27].

In our study, most tumors, 18 (86%), were

plurihormonal with preferential secretion of TSH, STH,

and/or PRL. None of the tumors secreted gonadotropin

and ACTH. “Pure” TSH-secreting tumors were found

only in 3 (14%) cases. Tumors with concomitant

expression of PRL or STH were associated with increased

blood level of RLP and clinical presentation of

acromegaly only in 4 (29%) and 3 (19%) cases,

respectively. The absence of clinical presentation of

hyperprolactinemia and/or acromegaly in other patients

with expression of PRL and/or STH was probably due to

secretion of biologically inactive forms of PRL and/or

STH.

According to the literature [1], most TSH-PAs

demonstrate expression of various receptors, including

receptors to TRH, dopamine, and somatostatin.

Expression of somatostatin receptors is often detected in

TSH-PA, especially in mixed STH-TSH-secreting

tumors. This explains the effective ability of somatostatin

analogs to lower TSH levels in patients with these tumors

[28, 29]. In our study, SSt5 expression was detected in

46% of cases and in most cases, it was accompanied by

STH expression in the tumor, while SSt5 expression was

rarely detected.

Surgery followed by radiotherapy is the basic method

of treatment for TSH-PA in the case of non-radical

resection [30, 31]. The literature provides no strict

criteria for remission after surgical treatment of

thyrotropinomas. However, clinical remission of

hyperthyroidism, normalization of thyroid hormone

levels, and regression of neurological symptoms are

considered as remission criteria. At the same time, these

biochemical and clinical criteria can be transitory and

are not considered as indicators of complete resection

[1]. Normalization of blood level of TSH also cannot be

an indicator of completeness, especially in patients with

normal preoperative level of TSH. Normalization of

α-subunit and/or the molar ratio of α-subunit and TSH

may be used to assess the effectiveness of therapy [32,

33]. Nevertheless, these two parameters are of low

sensitivity and are not applicable in patients with normal

preoperative levels. Triiodothyronine suppression test

and TRH stimulation test, which have optimal sensitivity

and specificity, were suggested as the most valid tests for

completeness of tumor resection [32, 33].

Undetectable blood level of TSH may be a good

indicator of radical resection. It is important to clarify

Fig. 4. Immunohistochemical expression of hormones by TSH-secreting pituitary adenomas.

TSH-posi�ve tumors (21)

“pure” TSH-3

TSH-STH-4 TSH-PRL-2 TSH-STH-PRL-12

Plurihormonal-18


that virtually undetectable TSH level should be

understood as its level below the functional sensitivity

threshold of detection method (<0.01 mIU/L). Indeed,

in our series of observations, postoperative decrease in

TSH levels below 0.01 mIU/L was characteristic of

completely resected tumors. However, all these cases

were accompanied by the development of

panhypopituitarism, including hypothyroidism, which

required administration of levothyroxine. Patients with

postoperative TSH levels of 0.01-0.1 mIU/L remained

euthyroid during the follow-up period (6—18 months).

Therefore, we arbitrarily defined TSH level of 0.1 mIU/L

and below as a marker of radical tumor removal.

However, these patients should be followed in the future

since delayed relapse of hyperthyroidism can occur.

Although adenomectomy is currently the treatment

of choice, treatment with somatostatin analogues is

believed to be effective in reducing TSH level,

normalization of fT4 and fT3 levels, and restoring

euthyrosis in 90% of cases [30, 34, 35]. In our study,

preoperative therapy with somatostatin analogues in 2

patients successfully normalized euthyrosis and the levels

of TSH and fT4.

The literature provides no data on the incidence of

TSH-PA recurrence. We observed 2 cases of continued

tumor growth in previously operated patients, which

required reoperation. In our series of observations, none

of the patients operated on at the Burdenko Neurosurgical

Institute had continued tumor growth during the

aforementioned follow-up period. Given the possibility

of delayed recurrence of hyperthyroidism in patients with

non-radical tumor resection, the possibility of stereotactic

irradiation of residual tumor tissue should be considered

even in the cases of euthyroid state. In the case of

complete resection of the tumor and the development of

hypothyroidism, tumor recurrence is unlikely at least

during the first years after the surgery.

Conclusion

In summary, TSH-secreting tumors are rare

representatives of pituitary adenomas. Early diagnosis of

these tumors and differential diagnosis, which rule out

other conditions accompanied by hyperthyroidism, are

of key importance. Surgical treatment is currently the

main method of treatment, however radical removal of

infiltrative tumors is impossible. Postoperative TSH level

of no more than 0.1 mIU/L can be considered as the

criterion of radical removal. It should be noted that

transient euthyrosis often occurs in patients with non-

radical tumor resection. However, the likelihood of

recurrence of hyperthyroidism nessessitates considering

the question of stereotactic irradiation of residual tumor

tissue. Therapy with somatostatin analogs can be effective

to achieve euthyrosis.


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Commentary

The article analyzes clinical cases of TSH-secreting tumor,

which is an extremely rare endocrine disease. Measurement of

TSH level is among the most commonly prescribed hormonal

tests. Increased TSH requires an accurate differential diagnosis,

because it can be caused by various endocrine disorders and

therefore it can require fundamentally different approaches to

the choice of treatment. In typical cases, thyrotropinoma is

accompanied by development of thyrotoxicosis with normal or

elevated TSH levels. Long-lasting untreated thyrotoxicosis

(including cases of misinterpretation of hormonal disorders)

leads to severe changes in many body systems (cardiovascular,

nervous, digestive, reproductive, etc.).

The authors provide very important guidelines for

practicing endocrinologists and neurosurgeons, characterizing

clinical cases of thyrotropinomas. They pay attention to the

very high percentage of misdiagnosis at the stage of outpatient

examination before admission to the Burdenko Neurosurgical

Institute; in some cases, patients with thyrotropinomas even

underwent thyroid resection.

All reported tumors were macroadenomas, in 91% of cases

they were endo-extrasellar. Most patients (76%) had clinical

signs of hyperthyroidism. Along with clinical signs of

hyperthyroidism, these patients also had various neurological

symptoms, including visual disturbances and cephalgic

syndrome. According to US study of the thyroid gland, 13

patients had various structural changes (diffuse goiter, nodular

goiter, diffusely nodular goiter). When combined with

thyrotoxicosis, this could contribute to inadequate differential

diagnosis of primary, rather than central thyrotoxicosis. When

comparing tumor growth patterns in 7 (71%) patients with a

history of thyroid surgery, most of them were diagnosed with

infiltrative growth. However, no statistical differences were

found, when comparing tumor growth patterns in the groups of

patients with and without history of thyroid surgery. In any


case, erroneous management of these patients may have

irreversible consequences.

Concomitant primary hypothyroidism, either

postoperative or resulting from chronic autoimmune thyroiditis,

with thyrotropinoma is one of the most disputable and

challenging problems. The authors regard these tumors as

secondary thyrotropinomas.

Complex hormonal examination of some patients also

detected other hormonal disorders. Tumors polymorphism was

further confirmed by immunohistochemical studies, where

isolated TSH expression was detected in only 14% of cases,

while the majority of tumors showed expression of TSH and

STH and/or PRL.

The paper points out that radical resection was possible in

33% of patients, having only endosellar and endo-suprasellar

tumor. There were no cases of complete resection of infiltrative

tumors. It would be proper to specify the tactics of management

of these patient, when radical adenomectomy is impossible.

It was found that normal postoperative level of TSH or its

decrease to 0.1 mIU/L, as well as transient postoperative

hypothyroidism are not the criteria of the effectiveness of tumor

removal. This proves once again that the verification of the

diagnosis and radical treatment pose significant problems. The

literature provides evidence of high efficacy of the use of

somatostatin analogues for thyrotropinomas, as also shown in

this work.

In this regard, the study of expression of dopamine and

somatostatin receptors in the resected tissue of pituitary

adenoma becomes highly important. The paper demonstrated

high incidence of expression of type 2 dopamine receptors and

type 5 somatostatin receptors.

In conclusion, the authors once again emphasize diagnostic

criteria of TSH-secreting pituitary tumor and differential

diagnosis of various types of thyrotoxicosis.

The article is extremely important, since it covers very

challenging issues of diagnostic criteria and management of

pituitary adenomas.

F.M. Abdulhabirova (Moscow, Russia)


ORIGINAL ARTICLES

doi: 10.17116/engneiro201680632-36

The Preliminary Results of Subthalamic Nucleus Stimulation after Destructive Surgery in Parkinson’s DiseaseE.A. KHABAROVA, N.P. DENISOVA, D.YU. ROGOV, A.B. DMITRIEV

Federal Center of Neurosurgery, Novosibirsk, Russia

Objective. The study was aimed at evaluating the efficacy of bilateral electrical stimulation (ES) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) after prior pallidotomy or ventrolateral (VL) thalamotomy.Material and methods. The study included 9 patients with bilateral STN ES, who previously underwent unilateral destructive surgery on the subcortical structures: pallidotomy (5 patients) and VL thalamotomy (4). Control group consisted of 9 patients with STN ES and without prior destructive surgery.Clinical and neurological examination included quantitative assessment of motor disturbances using the Hoehn—Yahr scale and Unified Parkinson's Disease Rating Scale (UPDRS). UPDRS was used to evaluate the motor activity (part III of the scale) and severity of drug-induced dyskinesia and motor fluctuations (part IV of the scale).Results. In the group of STN ES with preceding destruction of the subcortical structures, an improvement in motor functions in the early period (6 months) was 45%, and severity of drug-induced complications decreased by 75%. In a group of STN DBS without destruction, motor disturbances were improved by 61%, and drug-induced complications were decreased by 77%. Improvement in motor functions amounted to 51.9% in patients with preceding pallidotomy (GPi destruction) and 37.5% in a group with preceding VL thalamotomy.The equivalent dose of levodopa was reduced by 51.39%, from 1,008±346 to 490±194, in the study group and by 55.04%, from 963±96 to 433±160, in the control group.Conclusion. Bilateral STN neurostimulation is effective after unilateral stereotaxic destruction of the subcortical structures in PD patients.

Keywords: Parkinson’s disease, bilateral subthalamic nucleus neurostimulation, pallidotomy, VL thalamotomy.


Parkinson's disease (PD) or idiopathic parkinsonism

is the second most common (after Alzheimer's disease)

neurodegenerative disease [1]. Detectability of PD

among individuals older than 65 years is about 1%. Most

cases occur at the ages of 60—70 years, but in 15% of

cases, PD first occurs at the age of 45 years [1], i.e. in

workable and socially active population.

Despite the fact that the replacement dopaminergic

therapy is effective, more than 50% of patients develop

motor fluctuations within 2—5 years of therapy with

levodopa and the risk of dyskinesias increases by 10%

every year [2].

In this regard, development of complications or

resistance to dopaminergic therapy raises the question of

application of more effective non-drug methods to

correct parkinsonism symptoms. Neurostimulation of

subthalamic nucleus and ventrolateral thalamotomy and

pallidotomy are most commonly used for this purpose.

Surgical treatment of PD is effective at all stages of

the disease, but the modern trend is toward earlier

surgical treatment of patients, which prevents them from

losing social activity and enables returning to work [3, 4].

The moment when it is advisable to change from

pharmacotherapy to surgery still remains the main

disputable issue [4]. It is also being discussed, which

method should be offered to the patient: stimulation or

destructive interventions in the subcortical brain

structures. The unilateral thalamotomy and pallidotomy

effectively reduce the severity of tremor and rigidity on

the contralateral side, but this treatment has limitations.

Complications of VL thalamotomy in the form of

hemiparesis, lateropulsion upon walking, dysarthria, and

dysphagia (in the case of operation on the dominant

hemisphere) occur within the first few days after surgery

in almost 1% of operated patients and usually mostly

regress within the first weeks after the operation [5, 6].

The incidence and severity of perioperative complications

increase considerably after the second operation on the

opposite side. According to D. Louw [7], dysarthria and

severe mental disorders after bilateral VL thalamotomy

developed in 30—60% of cases. In 5—14% of cases,

pallidotomy can cause intraoperative and postoperative

complications in the form of partial or complete

hemianopsia, transient aphasia, and central facial palsy

[7—10]. In the case of bilateral symptoms, pallidotomy

on the contralateral side is associated with quite high (up

to 17%) risk of mental and speech disorders without

significant improvement of the results of the first

pallidotomy [7, 11].

Bilateral chronic electrical stimulation (ES) of the

subthalamic nucleus (STN) reduces the severity of

tremor and rigidity on both sides, as well as intensity of

hypokinesia, reduces the overall severity of movement

disorders and increases daily activity of PD patients,

which improves the quality of life of these patients [6, 12,

13].

Thus, pharmacotherapy often cannot solve the

problem of multiple PD symptoms and the use of

functional neurosurgery methods based on modulation

of hyperactivity of the subthalamic nucleus and medial


segment of the globus pallidus has been acknowledged as

the effective treatment of PD patients [12, 13].

At the same time, it is poorly understood how

effective is bilateral STN ES after destructive

interventions. Additionally, there is no reliable

information, whether the result of this procedure in

patients after destructive operations is comparable to that

in patients, who did not undergo destructive surgery on

the subcortical structures, and whether destructive

operation provides the patient with any long-term

advantages.

The objective of this research was to demonstrate our

own experience with bilateral neurostimulation of the

subthalamic nucleus in PD patients after previous

pallidotomy and VL thalamotomy and evaluate the

effectiveness of this method in the early follow-up period.


The study included PD patients with bilateral STN

ES after prior destructive surgery. The patients were

operated on at the department of functional neurosurgery

of the Federal Neurosurgical Center in Novosibirsk from

2013 to 2014.

The study included 9 patients (5 males, 4 females)

with STN ES, who previously underwent unilateral

destructive operations on the subcortical structures

(study group). Of these, pallidotomy was performed in 5

patients, VL thalamotomy was performed in 4 patients.

At the time of destructive surgery, average age of patients

was 54.9 years (47—64 years), at the time of STN ES —

55.9 years (47—65 years). Disease duration ranged from

5 to 20 years (mean duration, 12 years). The average

period between operations was 14 months (5 — 26

months).

Bilateral neurostimulation was carried out in the case

of progression of motor disorders.

The control group consisted of 9 patients (5 males, 4

females) with STN ES, which did not undergo destructive

surgery. The average age in the group was 54.9 years

(48—61 years). The disease duration was 7—16 years

(mean duration, 12 years).

Indications for surgery and selection criteria for STN

ES were identical in both groups. In patients with bilateral

neurostimulation, minimum follow-up time was 12

months, maximum — 30 months (average, 21 months).

Motor disorders were quantified in the clinical

neurological study before and after operations on the

following scale:

Hoehn-Yahr Scale (M. Hoehn, M. Yahr, 1967)

modified by Lindvall, Tetrud, and Langston (O. Lindvall

et al, 1987; J. Tetmd, J. Langston, 1987), which includes

both the conventional 5-point classification of severity of

parkinsonism and 1.5 and 2.5-point severity gradations.

The third edition of the unified PD evaluation scale

(Unified Parkinson's Disease Rating Scale, UPDRS),

(S. Fahn, R.Elton, 1987) contains 42 criteria. It estimates

motor activity (part III) and severity of drug-induced

dyskinesias and motor fluctuations (part IV). Each

criterion may score 0 to 4 points. The decrease in the

total score resulting from treatment was considered as a

positive dynamics.

There were no significant differences between study

and control group patients in age and duration of history.

In both groups, patients underwent a bilateral STN

ES. Neurostimulator programming was carried out

1 month after surgery. Neurostimulation parameters

were selected based on better clinical response of motor

manifestations and absence of side effects (dysarthria,

levodopa-dependent dyskinesia). No surgical

complications were observed in patients in the early

postoperative period.

Daily dose of dopaminergic preparations was

assessed based on determining the equivalent doses of

levodopa, which were calculated according to the

formula: 100 mg of levodopa = 130 mg of levodopa with

controlled drug release = 70 mg of levodopa + catechol-

O-methyltransferase inhibitor = 1 mg of pramipexole =

5 mg of ropinirole = 50 mg of piribedil [14]. Calculation

was made in the study and control groups before and 12

months after STN neurostimulation.

Results

In the study group, improvement of motor functions

after 12 months averaged 45% (22 to 50 UPDRS points)

(Table 1). Notably, 66.6% of patients in this group had a

dextral destruction (Table 2).

The number of UPDRS points (part III) 6 months

after the destructive intervention in this group decreased

by an average of 17% (33—65 points) (see Table 2). This

time interval for estimation was determined by the fact

that some of patients underwent STN ES in 6 months.

In the control group, improvement of motor

disorders in 12 months averaged 61%.

In 12 months, the severity of treatment complications

(medicinal dyskinesias and motor fluctuations) decreased

by an average of 75% in the main group and by 77% in the

control group (see Table 1).

Study group patients with bilateral STN ES had

various degrees of improvement depending on the

location of destruction. In patients with unilateral

pallidotomy, improvement of motor disorders was

51.9%, in the group with preceding VL thalamotomy —

37.5% (Table 3).

According to UPDRS (part III), clinical presentation

before ES was more severe in the control group patients

compared to that in the study group. This is due to

preserved clinical effect of unilateral stereotaxic

destruction in the study group, which occurred in the

form of milder rigidity, tremor, and dyskinesias on the

contralateral side.

The results of tests were similar in both groups 12

months after connection of neurostimulator (see


ORIGINAL ARTICLES

Table 1). Prior to STN ES, study group scored 51 UPDRS

points (35—65), control group — 74 points (63—82).

During STN ES, study and control groups scored 28

(22—50) and 29 points (20—42), respectively (see Table 1). After bilateral neurostimulation, equivalent

dose of levodopa decreased by 51.39%, from 1008±346

to 490±194, in the study group, and by 55.04%, from

963±96 to 433±160, in the control group.

Discussion

Stereotactic thermal destruction of the deep

structures of the brain is a technique that enabled safe

and effective suppression of PD symptoms at certain

stage of the disease [6].

Unilateral pallidotomy (destruction of the internal

segment of the globus pallidus, GPI) effectively treats

medicamentous dyskinesia in the contralateral limbs,

and, to a lesser extent, in the ipsilateral limbs, and also

reduces fluctuations of daily motor activity [9].

For many years, ventrolateral thalamotomy was used

to treat pharmacoresistant tremor in PD patients [9, 15,

16]. In this case, the incidence and severity of

perioperative complications significantly increase after

the second operation on the contralateral side [7].

Despite the excellent initial clinical effect in the case

of optimal positioning of destruction point, 10—15% of

patients resume preoperative symptoms within 1—2

years after the operation, often in the ipsilateral

extremities and axial muscles, which is associated with

progression of the disease [15]. Therefore, further surgery

is required in the future. Bilateral destructive interventions

are associated with high risk of complications. According

to J. Siegfried and B. Lippitz [17], chronic ES of

subcortical structures is the method of choice in PD

patients, who previously underwent stereotactic

destruction. This method uses autonomous implantable

systems, which enable chronic neurostimulation [18].

The main advantages of ES include minimal injury

to the brain tissue, which occurs during implantation of

the electrode, and reversibility of neurostimulation

effects. Modern neurostimulators enable noninvasive

correction of many parameters of stimulation program

(the use of monopolar or bipolar stimulation, various

intensity of electrical stimulation) [19]. Minimal

invasiveness of this techniques prevent from persistent

neurological complications characteristic of destructive

methods [12, 20].

Minimal invasiveness of this technique enables

single-stage bilateral surgery even in elderly patients [4,

20, 21]. The results of postmortem studies of operated

patients, who died of intercurrent diseases, have shown

that prolonged exposure to electrical stimulation does

not cause damage to the structures around the active

electrode [22]. The possibility of noninvasive correction

of neurostimulation parameters enables selecting an

individual effective and comfortable treatment program,

and eliminates side effects of neurostimulation [4].

The literature provides scarce information on the

effectiveness of STN ES in patients with previous

destructive interventions. The study of G. Kleiner-

Fisman et al. [23] showed that prior unilateral pallidotomy

does not impair the effectiveness of the subsequent

bilateral STN ES. In this study, electrophysiological

parameters also did not change significantly in the study

and control groups.

Our study showed that decrease in the severity of

motor disorders as assesses on the UPDRS scale was

lower in the group of patients with bilateral STN EN

preceded by unilateral pallidotomy and VL thalamotomy

as compared to the control group. This is due to preserved

clinical effect of previous unilateral stereotaxic

destruction, which occurs in the form of milder rigidity,

tremor and/or drug-induced dyskinesias on the side

contralateral to destruction area. Similar results were

obtained in the work of W. Ondo et al. [14]. In our study,

improvement in motor disturbances resulting from STN

ES were less pronounced in the group with prior VL

thalamotomy compared to the group with prior

destruction of GPi.

Assessment of the dynamics of drug-induced

complications showed that improvement was similar in

the study and control groups, which is consistent with the

aforementioned studies [14, 23]. Decrease in the

equivalent dose of levodopa in the study and control

Table 1. Characteristics of STN ES group patients, who previously underwent destruction, and STN EN group without prior destruction

ParameterStudy group with previous destruction

(n=9)

Control group without destruction

(n=9)

Age at the time of stimulation, years 55,58 (47—65) 54,88 (48—61)

Sex:

M 5 (56%) 5 (56%)

UPDRS part III prior to STN neurostimulation

(off) 51 (35—65) 74 (63—82)

UPDRS part III after STN neurostimulation in

12 months (off) 28 (22—50), 45% 29 (20—42), 61%

UPDRS part IV prior to STN neurostimulation 8 (5—11) 9 (5—12)

UPDRS part III after STN neurostimulation in

12 months 2 (1—3), 75% 2 (1—4), 77%


groups before STN EN and after 12 months of ES also

did not differ significantly.

W. Ondo et al. [14] believe that unilateral VL

thalamotomy may cause insufficiently accurate

positioning of STN EN electrode on the side of prior

destruction. A. Zaidel et al. [24] reported change and

decrease in neuronal activity of the subthalamic nucleus

after previous pallidotomy. In this regard, in patients

with preserved good clinical effect of destructive

operations or extensive destruction area, an option of

unilateral STN ES on the side contralateral to the

destruction area may be considered in the case of further

progression of the disease and emergence of indications

to STN ES.

Conflicting results of analyzed studies may be due to

a small number of patients with prior destruction of

subcortical structures in all these studies.

Methods of functional neurosurgery are currently an

integral part of the treatment of PD patients [25, 26].

Modern trends are towards earlier surgical treatment of

patients [3, 4]. In some patients, motor disorders can be

significantly reduced by unilateral stereotactic

interventions [14, 23]. However, disease progression is

accompanied by depletion of reserves of pharmacotherapy,

and some patients, who previously underwent destructive

operations, may require repeated surgery [27, 28].

Conclusion

The literature data and the results of our study show

that bilateral STN electrostimulation is effective and can

be used in patients with Parkinson's disease, who

previously underwent unilateral stereotactic destructive

operations on subcortical structures.


Table 2. Characteristics of patients with ES, who previously underwent stereotactic destruction (study group)

Preceding destruction Following STN ES

Sex

Age at the

time of

destruction,

years

Destruction

nucleus

Location

(R, right;

L, left)

Motor

disturbances

before

destruction

(off)

Motor

disturbances

after

destruction

in 6 months

(off)

Age at the

time of

stimulation,

years

Location

(B,

bilateral)

Motor

disturbances

before

neurostimulation

(off)

Motor disturbances

after

neurostimulation

in 6 months (off)

M 54 Gpi R 55 45 55 B 55 25

F 62 Vim L 59 54 63 B 54 25

M 53 Gpi L 67 62 53 B 62 31

M 47 Vim R 65 65 47 B 65 50

M 59 Vim R 57 33 60 B 35 22

F 64 Gpi L 52 40 65 B 50 28

F 47 Gpi R 57 46 50 B 54 22

M 51 Vim R 56 39 53 B 37 22

F 57 Gpi R 53 49 57 B 50 23

54,88

(47—64)

58 (52—67) 48 (33—

65)

55,88

(47—65)

51 (35—65) 28 (22—50)

Table 3. Study group with preceding stereotactic destruction

GPI VIM

Sex

Age at the

time of

stimulation,

years

Duration

of disease

history,

years

Motor

disturbances

before

neurostimulation

(off)

Motor

disturbances after

neurostimulation

in 6 months (off)

Sex

Age at the

time of

stimulation,

years

Duration

of disease

history,

years

Motor

disturbances

before

neurostimulation

(off)

Motor

disturbances after

neurostimulation

in 6 months (off)

M 55 15 55 25 F 63 11 54 25

M 53 13 62 31 M 47 5 65 50

F 65 12 50 28 M 60 11 35 22

F 50 15 54 22 M 53 20 37 22

F 57 10 50 23 3m/

1f

55,75

(47—63)

12 (5—

20)

48 (35—65) 30 (22—50)

2

m/3

f

56 (50—

65)

13 (10—

15)

54 (50—62) 26 (22—31)

51,85%


ORIGINAL ARTICLES

REFERENCES1. Levin OS, Fedorova NV. Parkinson's Disease. M.: Medpress-inform. 2011.

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5. Selby G. Stereotactic surgery. In: Koller WC. ed. Handbook of Parkinson’s disease. NY: Marsel Desser. 1992;529-544.

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7. Louw DF, Burchiel RG. Ablative therapy for movement disordes. Compli-

cations in treatment for movement disordes. Neurosurgery Clinics of North America. 1998;9:2:367-373.

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son’s disease by posterior GPi pallidotomy: 1-year results of a pilot study.

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Efficacy of bilateral pallidotomy. Neurosur Focus. 1997;2:3.

12. Tomsky AA, Bril EV, Shabalov VA, Fedorova NB. Electrical stimulation of

the subthalamic nucleus in Parkinson's disease. Voprosy neirokhirurgii imeni NN Burdenko. 2006;3:14-17. (In Russ.).

13. Walker HC, Watts RL, Schrandt CJ, Huang He, Guthrie CL, Guthrie BL,

Montgomery EB. J Activation of subthalamic neurons by contralateral sub-

thalamic deep brain stimulation in Parkinson disease. J Neurophysiol. 2011

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14. Ondo WG, Silay Y, Almaguer M, Jankovic J. Subthalamic Deep Brain

Stimulation in Patients With a Previous pallidotomy. Movement Disorders.

2006;21:8.

15. Fox MW, Ahlskog JE, Kelly PJ. Stereotactic ventrolateralis thalamotomy

for medically refractory tremor in post-levodopa era Parkinson’s disease

patients. Journal of Neurosurgery. 1991.

16. Tronnier V, Fogel W, Kronenbuerger M, Steinvorth S. Pallidal stimulation:

an alternative to pallidotomy? Neurosurgical Focus. 1997;2:3:E12.

17. Siegfried J, Lippitz B. Chronic electrical stimulation of the VL-VPL com-

plex and of the pallidum in the treatment of movement disorders: personal

experience since 1982. Stereotact. Funct Neurosurg. 1994;62:71-75.

18. Haris M. Complications of deep brain stimulation surgery. Mov Disord.

2002;17(3):S162−S166.

19. Paul S. Larson Deep Brain Stimulation for Movement Disorders. Neuro-therapeutics. 2014 July;11(3):465-474.

20. Bril EV, Tomsky AA, Gamaleya AA, Shabalov VA. Comparative study of

efficiency of neurosurgical treatment (electrostimulation of a subthalamic

nucleus) and pharmacotherapy in patients with developed stage of Parkin-

son's disease. Zhurnal nevrologii i psikhiatrii im SS Korsakova. 2014;6:55-61.

(In Russ.).

21. Deuschl G, Volkmann J, Krack P. Deep brain stimulation for movement

disorders. Mov Disord. 2002;17:S1.

22. Haberler C, Alesch F, Mazal PR, Pilz P, Jellinger K, Pinter MM, Hainfell-

ner JA, Budka H. No tissue damage by chronic deep brain stimulation in

Parkinson’s disease. Ann Neurol. 2000 Sep;48(3):372-376.

23. Kleiner-Fisman G, Fisman D, Zamir O, et al. Subthalamic nucleus deep

brain stimulation for Parkinson’s disease after successful pallidotomy: clini-

cal and electrophysiological observations. Mov Disord. 2004;19:1209-1214.

24. Zaidel A, Moran A, Marjan G. Prior pallidotomy reduces and modifies neu-

ronal activity in the subthalamic nucleus of Parkinson’s disease patients. Jour-

nal Compilation a Federation of European Neuroscience Societies and Black-

well Publishing Ltd. European Journal of Neuroscience. 2008;27:483-491.

25. Castrioto A, Lozano AM, Poon YY, et al. Ten-year outcome of subthalam-

ic stimulation in Parkinson disease: a blinded evaluation. Arch Neurol. 2011;68:1550-1556.

26. Zibetti M, Merola A, Rizzi L. Beyond Nine Years of Continuous Subtha-

lamic Nucleus Deep Brain Stimulation in Parkinson’s Disease. Mov Disord.

2011;26:13.

27. Esselink RA, de Bie RM, de Haan RJ, Lenders MW, Nijssen PC, Staal MJ,

Smeding HM, Schuurman PR, Bosch DA, Speelman JD. Unilateral palli-

dotomy versus bilateral subthalamic nucleus stimulation in Parkinson’ s

disease: one year follow-up of a randomized observer — blind multicentre

trial. Acta Neurochir (Wien). 2006;148(12):1247-1255.

28. Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, Kim JY, Cho SY, Lim YH,

Kim MR, Jeong SY, Jeon BS. The effects of bilateral subthalamic nucleus

deep brain stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008 Oct 15;273(1-2):19-24. Epub 2008 Jul 21

The article focuses on electrical stimulation (ES) of the

subthalamic nucleus (STN) in patients with Parkinson's

disease, who previously underwent destructive operation on the

deep structures of the brain. Modern literature provides

numerous publications dealing with ES of STN and the internal

segment of the globus pallidus. The effectiveness of this method

of treatment during short follow-up period was proved by a

number of randomized trials; there are also publications

reporting long-term results. A large number of studies cover the

issues of the effect of neurostimulation on various manifestations

of Parkinson's disease: motor symptoms, cognitive impairment,

balance and gait disorders, impulsive-compulsive disorders.

In recent years, destructive operations were abandoned in

favor of neurostimulation all over the world, which is very

promising due to the adjustability of its effect. However,

destructive operations still can be used in some cases with

predominance of unilateral manifestations of Parkinson's

disease. At the same time, patients who underwent destructive

operations can be sent for neurostimulation in the case of

disease progression.

In recent studies dealing with neurostimulation, previous

destructive operation was considered as an exclusion criterion.

However, there are several studies containing information on

the use of STN ES in small groups of patients, who previously

underwent destruction, and its effectiveness.

In general, this study is highly relevant and the results are

interesting and important for functional neurosurgery of

Parkinson's disease. Further studies will provide valuable data

to develop the optimal strategy of neurosurgical treatment of

Parkinson’s disease.

A.A. Tomskiy (Moscow, Russia)

Commentary


doi: 10.17116/engneiro201680637-48

Phase Contrast MRI-based Evaluation of Cerebrospinal Fluid Circulation Parameters in Patients with Foramen Magnum MeningiomasS.V. KONDRAKHOV, N.E. ZAKHAROVA, L.M. FADEEVA, S.V. TANYASHIN


Background. Meningiomas of the foramen magnum (FM) region account for 1.8 to 3.2% of all meningiomas. The international literature provides insufficient data describing the state of cerebrospinal fluid (CSF) circulation in these patients.Material and methods. We studied 38 patients with FM meningiomas aged 35 to 79 years (mean age, 56.7 years). Meningioma size averaged 30 mm (10—60 mm). Anterolateral meningiomas were observed in 29 patients, ventral — in 5 patients, and dorsal — in 4 patients. Twenty nine patients underwent surgery. All operated patients were examined before and after surgery. CSF circulation was studied using phase contrast MRI (PC-MRI).Results. The size and localization of FM meningiomas do not significantly affect CFS circulation parameters. Pyramidal symptoms, sensory disorders, and XIth cranial nerve dysfunction correlate with CFS circulation parameters. According to preoperative PC-MRI data, CFS circulation parameters were significantly higher in all patients with FM meningioma compared to normal values. Surgery was followed by decrease in the peak positive velocity, peak negative velocity, and range of maximum linear velocity amplitude. Positive and negative volumes and stroke volume did not change. Recovery dynamics of CFS circulation parameters was similar, regardless of surgery completeness. According to PC-MRI data, CFS circulation parameters did not reach normal values in all groups of operated patients.Conclusion. The results of investigation of CFS circulation in patients with FM meningiomas support the use of palliative surgery (partial resection, dural plasty, craniovertebral junction decompression) in the case of inoperable meningiomas.

Keywords: foramen magnum meningioma, surgery, cerebrospinal fluid circulation, phase contrast magnetic resonance imaging.


Meningiomas of the foramen magnum (FM) region

account for 1.8 to 3.2% of all meningiomas [1,2].

FM meningiomas are among the most challenging

pathologies in neurosurgery in connection with the fact

that the main arteries, cranial nerves, and medulla

oblongata are located in this area. Growing tumor

displaces and, in many cases, involves vertebral arteries

in its stroma.

Completeness of resection of meningiomas located

in this area depends on the location of the original

growth, density, and size of the tumor, arachnoid

membrane integrity, tumor invasion of vertebrobasilar

system vessels and caudal group of cranial nerves, applied

approach, and many other factors [3—7]. According to

different authors, total resection of FM meningiomas

was achieved in 70—96% of cases [8—11]. Therefore, the

rate of non-radical removal of meningiomas located in

his region is high.

Most publications dealing with craniovertebral

meningiomas describe the degree of completeness of

tumor resection. Available literature provides no reports

demonstrating the effect of tumor size and location on

the state of CSF circulation, severity and dynamics of its

impairment in patients with FM meningiomas and after

resection of these meningiomas.

The issues of the effect of the extent of meningioma

resection or decompressive surgery on the passability of

the subarachnoid cisterns of the craniovertebral junction

and the role of impairment and recovery of the CSF

circulation in the development of clinical manifestations

of this pathology and their changes were almost not

covered so far.

According to available preliminary data, the

effectiveness of tumor resection characterized by various

extent can be assessed based on both clinical signs and

reliable quantitative values of CSF circulation.

Phase-contrast MR is the main non-invasive imaging

method for CSF spaces. As opposed to MR and CT

cisternography, this technique can be used to assess not

only anatomical characteristics of the CSF system and

geometry of CSF spaces with slow CSF motion, but also

to visualize fast CSF motion [12—16]. Thus, phase

contrast MRI provides the most adequate assessment of

CSF dynamics without limitation to the craniovertebral

junction [17—22]. The literature [23] provides data on

the evaluation of CSF circulation using phase contrast

MRI in patients with syringomyelic and arachnoid cysts.

Elucidation of the mechanisms of CSF circulation

disorders in patients with FM meningiomas will clarify

the pathogenesis of clinical manifestations of the disease

caused by direct tumor action on the neural structures

and impaired CSF circulation.

The research was aimed at studying the characteristics

of the CSF circulation in patients with meningiomas of

the craniovertebral junction and changes in the CSF

circulation parameters depending on the extent of the

surgery.

The study was aimed at:

— Evaluating CSF circulation disturbances

depending on the size of FM meningiomas;

— Assessing CSF circulation disturbances

depending on the location of meningiomas (anterior,

anterolateral, posterior);


ORIGINAL ARTICLES

— Assessing the impact of CSF circulation

disorders on the severity and dynamics of clinical

symptoms in patients with FMR meningiomas;

— Assessing the severity of CSF circulation

disorders before and after surgery and the nature of

changes in CSF circulation parameters, depending on

the extent of surgical intervention.

Materials and methods

The study was based on the results of examination of

38 patients with FM meningiomas aged 35 to 79 years

(mean age, 56.7 years). In our series, most patients were

45—50 and 60 —65 years old (Fig. 1).

Maximum tumor size was calculated based on

contrast enhanced T1-weighed MRI anatomical slices in

three projections. Maximum size of meningiomas ranged

10 to 60 mm, median 30 mm. Distribution of the

maximum size of meningiomas is shown in Fig. 2.

Most patients in our series had anterolateral FM

meningiomas, a total of 29 cases. Ventral meningiomas

were detected in 5 patients, dorsal — 4 (Fig. 3).

Surgery was conducted in 28 patients. The extend of

the surgery varied from total resection to biopsy

accompanied by dural plasty with aponeurosis. One

patient underwent ventriculoperitoneal shunting due to

occlusive hydrocephalus. Nine patients had not been

operated on. Five of them underwent radiotherapy. In 1

patient, operation was canceled due to the burdened

somatic status. In 3 cases, surgery was not proposed due

to small tumor size and minimal symptoms. These

patients were followed. We used the classification

proposed by K. Amautovic [24, 25] to assess the

completeness of tumor resection:

— total resection (gross-total resection) — complete

tumor resection, including the involved DM fragments.

It corresponds to grade I tumor resection according to

Simpson's classification (Simpson I);

— almost total resection (near-total resection) — in

the case of preservation and coagulation of the tumor at

the DM matrix. It corresponds to grade II tumor resection

according to Simpson's classification (Simpson II);

— subtotal resection — resection of more than 60%

of tumor volume It corresponds to grade III tumor

resection according to Simpson's classification (Simpson

III);

— partial resection — resection of less than 60% of

the tumor, including biopsies and simple decompression.

It corresponds to grade IV—V tumor resection according

to Simpson's classification (Simpson IV—V).

The examples of total and subtotal resection of

meningiomas are shown in Fig. 4 and 5.

Distribution of patients according to the extent of

tumor resection is shown in Fig. 6.

All operated patients underwent preoperative and

postoperative (in 3—6 months) examination. Nine

30 35 40 45 50 55 60 65 70 75 80 850

1

2

3

4

5

6

7

8

9

Age, years

Cas

e N

o

Fig. 1. Patients’ age distribution.


patients, who had not been operated on, were examined

once.

The studies were carried out on Signa HDxt MR

tomograph (General Electric Medical Systems) using the

magnetic field strength of 1.5 T.

All patients underwent MRI in the following modes:

– standard T1 and T2-weighted MRI in the axial and

sagittal planes; they were obtained using spin echo pulse

sequence, SE (600/20) and FastSE (4500/84);

— 3D T2-weighed MRI modes (3D-CUBE mode,

which provides a clear view of the outline of the

subarachnoid spaces, and FIESTA mode, showing

pulsatile CSF movement);

— phase contrast MRI (PC-MRI) with reference to

the cardiac cycle based on the PC-MRI pulse sequence

with parameters TR 26/TE 11/FA 20 gy, 256/160 image

matrix, in two replicates. The slice (4 mm thick) was

selected at C2—C3 level, perpendicular to the vertebral

canal, with FOV = 200 mm. The average scan time was

3—4 min.

Heart contraction curve was recorded using

peripheral plethysmograph. A total of 16 images per

cardiac cycle were recorded, corresponding to the

different phases of the cardiac cycle. Spin velocity

encoding (VENC-Velocity encoding) averaged 15 cm/s.

In the case of artifacts, VENC could be changed in the

range from 0 to 20 cm/s. Data were processed in offline

mode based of the Report Card software package. Region

of interest in the intradural space was selected based on

PC-MRI (Fig. 7), stroke volume, linear and volumetric

velocity of CSF circulation were calculated as a function

of the cardiac cycle phase (Fig. 8).

Data processing using Report Card software provided

the following characteristics of the CSF circulation:

positive peak velocity, negative peak velocity, positive

volume, negative volume, amplitude range of the

maximum linear velocity, and stroke volume. The

physical meaning of CSF circulation parameters obtained

by PC-MRI is as follows:

— positive peak velocity — maximum linear

velocity of CSF in the craniocaudal direction;

— negative peak velocity — maximum linear

velocity of the CSF in the caudocranial direction;

— amplitude range of the peak velocity — the range

of maximum linear velocity variation in one cardiac

cycle.

These three parameters represent velocity

characteristics of CSF circulation, wherein the latter one

is derived from the positive and negative velocities.

Positive volume — the amount of CSF passing

through the axial slice at C2—C3 during systole.

Negative volume — the amount of CSF passing

through the axial slice at C2—C3 during diastole.

Stroke volume — the amount of CSF passing through

the axial slice at C2—C3 during one cardiac cycle.

0 5 10 15 20 25 30 35 40 45 50 55 60 650

1

2

3

4

5

6

7

8

9

Maximum size, mm

Cas

e N

o

Fig. 2. Distribution of the maximum size of meningiomas.


ORIGINAL ARTICLES

Positive and negative volume and stroke volume are

volumetric characteristics of CSF circulation. As in the

case of linear velocity, stroke volume is derived from the

positive and negative volume.

Normal values of the main indices at C2—C3 were

obtained based the study including healthy volunteers,

which was previously performed at the Burdenko

Neurosurgical Institute (Table 1) [26].

Statistical processing of the material used Descriptive

Statistics methods (scattering diagram, distribution of

variables, mean and standard deviation) and

nonparametric statistics methods describing the ordinal

values (linear relationship between the Spearman’s

parameters, group analysis with calculation of confidence

probability of intergroup differences using Mann Whitney

test, medians, and percentiles). The data were processed

using Statistica v.10 software.

Results

Preoperative characteristics of CSF circulation in

patients with FMR meningiomas.

We used MRI to visualize CSF movement through

the third ventricle, cerebral aqueduct, large cistern, and

spinal canal. Fig. 9 shows an example of the preoperative

examination of patient S., 46 years old, who was

diagnosed with FM meningioma.

Table 2 shows the average and median values of CSF

circulation parameters in 38 patients.

Anterolateral76%

Ventral13%

Dorsal11%

Fig. 3. Location of FM meningiomas in the analyzed series.

Fig. 4. Total resection of FM meningioma. a, b — preoperative contrast enhanced T1-weighed MRI of the brain (sagittal and axial projections); d, e — contrast enhanced T1-weighed MRI of the brain after total

resection (gross-total resection, sagittal and axial projection); c —overall view of the tumor after opening of the dura mater and arachnoid membranes; f — after total

removal of the tumor node (1 — cerebellum, 2 — arachnoid, 3 — tumor, 4 — caudal group of cranial nerves, 5 — resected tumor bed, 6 — medulla oblongata, 7 — loop

of the posterior inferior cerebellar artery).


Comparative analysis of quantitative characteristics

of СSF circulation at C2—C3 in apparently healthy

individuals and patients with CSF meningiomas showed

СSF circulation disorders in the form of statistically

significant increase in all investigated parameters

(p<0.05) in patients with meningioma.

The relationship between meningioma size and CSF circulation parameters

We found no correlation between meningioma size

and CSF circulation parameters.

Examples of various relationships between tumor

size and CSF circulation parameters are shown in Fig. 10

and 11.

The relationship between CSF circulation and location of meningiomas

CSF circulation parameters were compared in three

groups of patients depending on tumor location (ventral,

anterolateral, and dorsal) based on Mann-Whitney test.

The analysis found that tumor location, as well as FM

meningioma size, has no significant effect of CSF

circulation parameters.

Fig. 5. Subtotal resection of FM meningioma. a, b — preoperative contrast enhanced T1-weighed MRI of the brain (sagittal and axial projections); d, e — contrast enhanced T1-weighed MRI of the brain after

subtotal resection (subtotal resection, sagittal and axial projections); c —overall view of the tumor after opening of the dura mater and arachnoid membranes; f —

intraoperative view after subtotal removal of the tumor (1 — cerebellum, 2 — arachnoid, 3 — meningioma, 4 — caudal group of cranial nerves, 5 — medulla oblongata,

6 — meningioma remnants tightly adherent to the vertebral artery, 7 — loop of the posterior inferior cerebellar artery).

Partial25%

Near-total21%

Gross-total29%

Subtotal25%

Fig. 6. The completeness of meningioma resection in 28 patients.


ORIGINAL ARTICLES

Clinical manifestations and their correlation with CSF circulation parameters

Clinical presentation of FM meningiomas consists of

various symptoms. We combined these symptoms into

several characteristic syndromes:

1) cerebellar syndrome — dizziness, cerebellar

ataxia, impaired statics, gait, and coordination;

2) cerebral symptoms are caused by increased

intracranial pressure. They manifest in the forms of

headache, dizziness, nausea, and vomiting;

3) bulbar syndrome — hoarseness, nasal voice,

decreased palatal and pharyngeal reflexes, choking when

swallowing, tongue deviation toward the affected muscle,

atrophy and fibrillar twitching of a half of the tongue.

This syndrome is associated with a direct effect of the

tumor on the medulla oblongata and exiting roots of the

IX, X, and XII pairs of cranial nerves;

4) pyramidal disorders — symptom resulting from

tumor compression of the pyramidal pathways at the

level of medulla oblongata and spinal cord and

manifesting in the form of various severity of conduction

motor disorders;

5) sensitivity disorders. These disorders are mainly

caused by direct effect of meningiomas on the afferent

pathways of the medulla oblongata and superior cervical

spinal cord;

6) cervical syndrome — presents with restricted

neck mobility, pain in the cervico-occipital area, head

tilt;

7) dysfunction of the XIth pair of cranial nerves

presents with paresis, plegia, atrophy of

sternocleidomastoid and trapezius muscles.

Preoperative and postoperative distribution of the

incidence of the aforementioned syndromes and their

relationship to the CSF circulation parameters, as well as

the significance of differences in the subgroups are

summarized in Tables 3 and 4.

Preoperative positive and negative volume and stroke

volume significantly differ (p<0.05) in the subgroups of

patients with/without pyramidal symptoms. In the

subgroup of patients having pyramidal symptoms, these

values are significantly lower compared to patients

without pyramidal disturbances. In our opinion, this may

be due to the characteristics of the tumor node

configuration. Local effect on the anterolateral surface of

the medulla oblongata is characterized by more

pronounced clinical manifestations in the case of smaller

tumor compared to larger tumor volume, having no

direct contact with the anterolateral surface of the

medulla oblongata. Positive and negative peak velocity

and range of maximum velocity amplitude do not depend

on the neurological symptoms (p> 0.05).

Postoperative values (29 patients) of the positive and

negative peak velocity and range of the maximum velocity

amplitude are significantly higher (p<0.05) in patients

having sensory disorders and dysfunction of the XIth pair

of cranial nerves. No statistically significant correlation

Fig. 7. Axial slice at C2—C3. a — the spinal cord; b — “area of interest” in the intradural space.

Table 1. Quantitative characteristics of CSF circulation at C2—C3 in healthy volunteers

CSF circulation parameter according to

PC-MRIValues

Amplitude range of the maximum linear

velocity, cm/s

7,2±0,68

Stroke volume, ml 1,04±0,37

Fig. 8. PC-MRI study protocol.


Table 2. Preoperative quantitative characteristics of CSF circulation at C2—C3 in patients with FM meningiomas

CSF circulation parameter Median Std. Dev. Median 25,000 th 75,000 th

Positive peak velocity, cm/s 10,97 4,7 12,2 6,67 14,8

Negative peak velocity, cm/s 9,89 4,59 9,77 5,33 14

Positive volume, ml 0,99 0,48 0,93 0,75 1,39

Negative volume, ml 0,84 0,49 0,92 0,38 1,16

Amplitude range of the maximum linear velocity, cm/s 20,86 8,61 21,38 16,23 29

Stroke volume, ml 1,83 0,83 1,83 1,43 2,41

of other CSF circulation parameters with clinical

presentation was found (p>0.05). In some cases, this is

due to the small number of observations. For example,

only one patient was initially diagnosed with hypertensive-

hydrocephalic syndrome, which regressed after surgery,

and therefore this parameter could not be reliably

evaluated.

Postoperative dynamics of CSF circulation in patients with FM meningiomas

Examination of 28 patients before and 3—6 months

after tumor resection resulted in the following quantitative

values of the main CSF circulation parameters at C2—

C3 (Tables 5 and 6).

Comparative analysis of preoperative and

postoperative medians of the main CSF circulation

parameters showed that positive peak velocity, negative

peak velocity, and amplitude range of the maximum

linear velocity are significantly lower after surgery. There

is no significant differenced in the positive and negative

volume and stroke volume (p>0.05). Therefore, CSF

circulation improves after surgery in terms of velocity

characteristics and remains unchanged in terms of

volumetric characteristics (Table 7).

The effect of the extent of surgical intervention on the recovery of CSF circulation

We compared the medians of all significantly varying

parameters of CSF circulation (peak positive velocity,

peak negative velocity, amplitude range of maximum

linear velocity) between the four groups of patient

according to completeness of tumor resection (Table 8,

Fig. 12).

The resulting values demonstrate that significant

improvement of CSF circulation parameters was

achieved in the case of total resection; they were better

than postoperative values after almost total and subtotal

tumor resection. The group with partial resection was the

second best in terms of recovery of CSF circulation

parameters.

Comparative analysis of the medians of the main

parameters of preoperative and postoperative CSF

circulation has shown that surgery results in significantly

reduced positive peak velocity, negative peak velocity,

amplitude range of the maximum linear velocity. There

was no significant changes in the positive and negative

volume and stroke volume (p>0.05). Therefore, CSF

circulation improves after surgery in terms of velocity

Рис. 9. a — FIESTA MRI: CSF circulation unit is visualized on the anterior surface of the brain stem (at the FM); b — axial peak PC image at C2—C3 during systole. A narrow high-signal band in the intradural space (shown by arrow) corresponds to CSF movement in the craniocaudal direction during systole; c — axial peak PC image at C2—C3 during diastole. A narrow high-signal band in the intradural space (shown by arrow) corresponds to CSF movement in the caudocranial direction during diastole.


ORIGINAL ARTICLES

characteristics and remains unchanged in terms of

volumetric characteristics (Table 7).

It should be noted that postoperative velocity

characteristics of CSF circulation improve according to

PC-MRI, but does not reach normal values, regardless of

the completeness of resection.

Discussion

Publications dealing with investigation of CSF

circulation based on PC-MRI studies are dominated by

studies in patients with Chiari malformation [13—16]

and hydrocephalus [22, 27]. Available literature provides

no studies of CSF circulation in patients with FM

meningioma.

Chiari malformation is the most similar to FM

tumors in terms of the pathogenetic basis of CSF

circulation changes. Analysis of the literature

demonstrates conflicting data on CSF circulation

parameters at the superior cervical level in both healthy

volunteers and patients with type I Chiari malformation

before and after the operation [13—16, 28, 29]. This may

be caused by the following reasons: different specifications

of MR imager; measurements at different levels;

heterogenous age composition of the patients under

study; the study did not take into account the

degenerative-dystrophic changes affecting CSF

circulation processes; many authors provide not all CSF

circulation parameters, which makes it difficult to

compare the results.

Fig. 10. Anterolateral FM meningioma sized 24 mm. All CSF circulation characteristics are 2—3-fold higher than normal.a — contrast-enhanced T1-weighed MRI, sagittal view; B — contrast-enhanced T1 MRI, axial view.

Fig. 11. Anterolateral FM meningioma sized 38 mm. All CSF circulation characteristics are within the normal range. a — T1-weighed MRI, sagittal view; b — T2-weighted MRI, axial view.


Tabl

e 4.

Pos

tope

rativ

e ne

urol

ogic

al s

ympt

oms

in 2

9 pa

tient

s w

ith F

M m

enin

giom

as. M

edia

ns o

f C

SF c

ircu

latio

n pa

ram

eter

s at

C2—

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depe

ndin

g on

the

pre

senc

e/ab

senc

e of

a c

erta

in s

ympt

om

com

plex

, as

wel

l as

the

sign

ifica

nce

of d

iffer

ence

s be

twee

n th

e su

bgro

ups

Sy

mp

tom

co

mp

lex

Pea

k p

osi

tive v

elo

cit

yP

ea

k n

ega

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elo

cit

yP

osi

tive v

olu

me

Nega

tive v

olu

me

Am

pli

tud

e r

an

ge,

ma

x..

Str

ok

e v

olu

me

n%

Med

ian

+M

edia

n–

pM

edia

n+

Med

ian

–p

Med

ian

+M

edia

n–

pM

edia

n+

Med

ian

–p

Med

ian

+M

edia

n–

pM

edia

n+

Med

ian

–

Cere

bell

ar

syn

dro

me

11

37

,98

,21

9,7

0,6

8,5

9,6

80

,67

0,5

60

,80

,76

0,7

0,6

0,5

91

7,8

61

9,3

10

,62

1,2

1,47

Cere

bra

l

syn

dro

me

72

4,1

9,8

9,6

30

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9,6

59

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0,8

50

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0,7

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80

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17

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2

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17

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19

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0,6

31

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1,2

Py

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dis

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41

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8,8

80

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58

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70

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0,6

10

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1,3

17

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0,1

90

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1,21

Sen

sory

dis

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82

7,6

11

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7,4

60

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11

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50

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10

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0,0

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1,2

6

Cerv

ica

l

syn

dro

me

31

0,3

13

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0,3

41

2,9

9,6

50

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1,4

20

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0,2

30

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0,6

10

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26

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60

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1,4

71,

2

Dy

sfu

nc

tio

n o

f

XI

14

48

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0,7

96

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0,0

11

0,1

58

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0,0

80

,86

0,5

70

,19

0,8

60

,50

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20

,69

14

,54

0,0

31

,57

1,15

Tabl

e 3.

Pre

oper

ativ

e ne

urol

ogic

al s

ympt

oms

in 3

8 pa

tient

s w

ith F

M m

enin

giom

as. M

edia

ns o

f C

SF c

ircu

latio

n pa

ram

eter

s at

C2—

C3

depe

ndin

g on

the

pre

senc

e/ab

senc

e of

a c

erta

in s

ympt

om

com

plex

, as

wel

l as

the

sign

ifica

nce

of d

iffer

ence

s be

twee

n th

e su

bgro

ups.

Sy

mp

tom

co

mp

lex

Pea

k p

osi

tive v

elo

cit

yP

ea

k n

ega

tive v

elo

cit

yP

osi

tive v

olu

me

Nega

tive v

olu

me

Am

pli

tud

e r

an

ge,

ma

x.

Str

ok

e v

olu

me

n%

Med

i-

an

+

Med

i-

an

–p

Med

i-

an

+

Med

i-

an

–p

Med

i-

an

+

Med

i-

an

–p

Med

i-

an

+

Med

i-

an

–p

Med

i-

an

+

Med

i-

an

–p

Med

i-

an

+

Med

i-

an

–

Cere

bell

ar

syn

dro

me

26

68

,41

0,2

01

4,6

50

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9,6

41

0,8

40

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1,8

61

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0,6

40

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0,8

50

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20

,60

23

,70

0,5

11

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1,7

8

Cere

bra

l

syn

dro

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16

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3,4

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10

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9,6

20

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0,3

71

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0,7

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21

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0,7

01

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1,71

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lba

r

syn

dro

me

61

5,8

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12

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0,7

81

0,7

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30

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0,9

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0,9

00

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52

3,4

82

1,3

80

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41,

87

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10

26

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0,7

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00

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20

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71

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sory

dis

ord

ers

11

28

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01

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8,0

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1,3

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1,7

11,

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Dy

sfu

nc

tio

n o

f

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51

3,2

12

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0,6

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3,3

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0,3

50

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0,9

00

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1,0

60

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0,5

22

8,0

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30

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21,

81

Not

e. I

n T

ab

les

3 a

nd

4:

n —

th

e n

um

ber

of

pa

tien

ts,

% —

sy

nd

rom

e o

cc

urr

en

ce r

ate

; m

ed

ian

+ —

med

ian

of

resp

ec

tive i

nd

ices

in p

ati

en

ts h

avin

g t

he c

om

ple

x o

f sy

mp

tom

s; m

ed

ian

– —

med

ian

of

resp

ec

tive i

nd

ices

in p

ati

en

ts w

ith

ou

t

sym

pto

m c

om

ple

x;

p<0

.05

.


ORIGINAL ARTICLES

We used the technique that was previously developed

at the Burdenko Neurosurgical Institute and

demonstrated in the article of N.V. Arutyunov reporting

the study of CSF circulation in patients with type I Chiari

malformation [26]. According to the findings of N.V.

Arutyunov et al. (2009), all preoperative CSF circulation

parameters in patients with type I Chiari malformation

were significantly lower than normal values. After

surgery, all CSF circulation characteristics significantly

increase and reach normal level. In our study, the reverse

trend was observed in patients with FM meningiomas

before surgery: all CSF circulation parameters were

above normal. Our data, demonstrating increase in

velocity values of CSF circulation, are in agreement with

hydrodynamic continuity law (Castelli’s law), whereby

the flow rate of the fluid in pipes is inversely proportional

to their cross-section. In our opinion, increase in

volumetric characteristics of CSF circulation is due to

turbulent motion of the CSF below meningiomas (C2―

C3). After surgery, velocity characteristics of CSF

circulation (peak positive and negative velocity,

amplitude range of the maximum linear velocity) in

patients with FM meningiomas significantly decreased,

but did not reach normal values; volumetric parameters

(positive and negative volume, stroke volume) did not

changed. Since the follow-up study was conducted 3—6

months after the operation, these CSF circulation

characteristics can be attributed to the development of

postoperative cicatrical changes.

Conclusion

According to PC-MRI, all preoperative CSF

circulation parameters in patients with FMR

meningiomas exceed normal values. The relationship

between these parameters and tumor size and location

was not established. We found only correlations between

some parameters and clinical manifestations of the

disease, which can indirectly indicate the role of tumor

configuration in CSF circulation disorders. After the

operation, velocity characteristics of CSF circulation

decrease, volumetric characteristics remain unchanged.

Table 5. Quantitative characteristics of CSF circulation at C2—C3 in 28 patients with FM meningiomas before tumor resection

CSF circulation parameter Median Std.Dev. Median 25,000 th 75,000 th


Peak negative velocity, cm/s 10,85 4,47 11,90 6,46 14,52



Amplitude range of maximum linear velocity, cm/s 22,97 8,16 23,70 17,27 29,26

Stroke volume, ml 1,92 0,80 1,91 1,56 2,28

Table 6. Quantitative characteristics of CSF circulation at C2—C3 in 28 patients with FM meningiomas after tumor resection

CSF circulation parameter Median Std.Dev. Median 25,000 th 75,000 th


Peak negative velocity, cm/s 8,88 3,87 9,67 4,96 11,40



Amplitude range of maximum linear velocity, cm/s 17,84 7,65 19,56 9,71 24,05

Stroke volume, ml 1,50 0,90 1,27 1,04 2,15

0

5

10

15

20

25

Gross-total Near-total Subtotal Partial

Positive peak velocity, cm/s

Peak negative velocity, cm/s

Amplitude range of maximum linear velocity, cm/s

7,15 6,36

13,5310,63 9,3

20,53

11,7 10,2

23,4

9,63 9,68

19,31

Fig. 12. CSF circulation recovery as a function of the extent of tumor resection according to PC-MRI.


Table 7. Median of preoperative and postoperative quantitative characteristics of the CSF circulation at C2 —C3 and probability values in patients with FM meningiomas

CSF circulation parameter Median 25,000 th 75,000 th Median 25,000 th 75,000 th p-value

Positive peak velocity, cm/s 14,20 10,05 15,05 9,75 4,66 12,45 0,0058

Peak negative velocity, cm/s 11,90 6,46 14,52 9,67 4,96 11,40 0,039

Positive volume, ml 1,01 0,82 1,44 0,78 0,42 1,18 0,096

Negative volume, ml 0,97 0,46 1,16 0,66 0,21 1,14 0,29

Amplitude range of maximum linear

velocity, cm/s 23,70 17,27 29,26 19,56 9,71 24,05 0,0072

Stroke volume, ml 1,91 1,56 2,28 1,27 1,04 2,15 0,12

Table 8. Quantitative characteristics of CSF circulation (median and percentiles) at C2—C3 as a function of the extent of surgical intervention

ParameterExtent of tumor resection

Total Near-total Subtotal Partial

Positive peak velocity, cm/s 7,15 (4,39—11,7) 10,63 (5,15—12,6) 11,7 (6,71—13,2) 9,63 (3,93—9,88)

Peak negative velocity, cm/s 6,36 (4,77−10,56) 9,3 (4,9—10,1) 10,2 (9,65—14,30) 9,68 (3,25—10,4)

Amplitude range of maximum linear velocity,

cm/s 13,53 (9,25—22,13) 20,53 (9,88—21,5) 23,4 (16,36—27,4) 19,31 (7,27—20,28)

Decrease in these values does not depend on the

completeness of tumor resection.

The small number of patients and differently directed

changes in the velocity and volumetric parameters

complicate interpretation of the results and indicate that

routine use of PC-MRI in the treatment of FM

meningiomas is inappropriate at this stage.

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proach for large anterior/anterolateral foramen magnum tumours. Br J Neurosurg. 2004;18:164-167.

doi: 10.1080/02688690410001681028

25. Arnautović KI, Al-Mefty O, Husain M. Ventral foramen magnum menini-

giomas. J Neurosurg. 2000;92:71-80.

doi: 10.3171/spi.2000.92.1.0071

26. Arutyunov NV, Korniyenko VN, Reutov AA, Fadeyeva LM. Cerebrospinal

fluid flow at the upper cervical spinal level in health and Chiari I

malformation. Vestnik Rentgenplogii i radiologii. 2009;4-6:37-42. (In

Russ.).

27. Henry-Feugeas M, Idy-Peretti I, Baledent O, Cornu P, Lejay H, Bittoun J,

Schouman-Claeys AE. Cerebrospinal fluid flow waveforms: MR analysis in

chronic adult hydrocephalus. Invest Radiol. 2001;36:146-154.

doi: 10.1097/00004424-200103000-00003

28. Hofman E, Warmuth-Metz M, Bendszus M, Solymosi L. Phase-contrast

MR imaging of the cervical CSF and spinal cord volumetric motion analysis

in patients with Chiari I Malformation. AJNR. 2000;21:151-158.

29. Meadows J, Kraut M, Guarnieri M, Haroun RI, Carson BS. Asymptom-

atic Chiari type I malformations identified on magnetic resonance imaging.

J Neurosurg. 2000;92:920-926.

doi: 10.3171/jns.2000.92.6.0920

In this article, the authors focus on a rare pathology,

namely meningioma of the foramen magnum (FM) region,

which accounts for 3.2% of all meningiomas, and CSF

circulation status after surgical treatment, which is scarcely

described in the literature.

The Materials and Methods summarizes the experience in

38 patients with anterolateral (29 patients), ventral (5), and

dorsal (4) FM meningiomas. A total of 29 patients were

operated on. All operated patients were examined before and

after surgery. CSF circulation was studies using phase contrast

MRI (PC-MRI).

The study demonstrated that the size and location of FM

meningiomas did not significantly affect the characteristics of

CSF circulation. Neurologic deficit correlated with CSF

circulation parameters. Most importantly, the dynamics of

recovery of CSF circulation parameters is the same regardless

of the completeness of surgery. In all groups of operated

patients, CSF circulation characteristics do not reach normal

values as evidenced by PC-MRI, which pathogenetically

justifies the use of palliative surgery (partial resection, dural

plasty, decompression of the craniovertebral junction) in the

case of inoperable meningiomas.

The article as a whole, references, and summary provide

detailed presentation of the matter under investigation. This

study included a sufficient number of patients, which makes it

statistically significant, summarizes the experience with PC-

MRI and the influence of radical surgery on the CSF

circulation parameters in patients with FM meningiomas, and

proves the possibility of palliative surgery.

L.M. Zaytsev (Moscow, Russia)

Commentary


doi: 10.17116/engneiro201680649-51

Application of Resorbable Plates for Fixation of a Laminotomy FlapYU.V. KUSHEL’, YU.D. BELOVA, A.R. TEKOEV


The paper describes a new technology ― application of resorbable plates and pins for securing a laminotomy flap in children’s neurosurgery. Four patients were operated on at our clinic. We describe in detail a surgical technique and compare it with a traditional fixation technique using ligatures.

Keywords: fixation, resorbable plates and pins, ultrasonic tip, laminotomy.


Laminotomy is widely used for surgical access to

pathologies of the spinal canal [1]. The duration of

laminotomy, especially in case of multilevel access, is

rather short (much shorter than standard laminectomy).

However, the process of fixing the laminotomy flap can

take a lot of time, often as much as the time required for

all previous stages of the surgery. The technology used for

fixing the laminated flap is either ligatures through each

arch or titanium mini-plates [1, 2]. We deliberately did

not use titanium mini-plates in our practice for several

reasons: difficulty of achieving good fixation of screws in

children’s thin and soft vertebrae arches and issues with

relaminotomy in the event of relapse of the disease.

Therefore, until recently our main method of fixation

was ligatures [1, 3].

Resorbable plates and pins (biodegradable plates and

special screws for them) are made of amorphous polymer

consisting of D-lactide and L-lactide in equal proportions

[4, 5]. Biodegradation requires about 90 days and occurs

by hydrolysis. The screws used for this method differ

from the “true” ones by the absence of threads and

therefore there is no need use a screwdriver. In essence,

they are pins that can be softened using a special

ultrasonic nozzle and subsequently “flow into” the

bone’s diploque, which allows them to become fixated in

it once the ultrasonic action is stopped and they solidify.

The technology is simple and convenient. In addition,

the plate itself is also softened by heating at a temperature

of 60 °C and can be modeled “in situ”. The manufacturer

positions these products for cranial and maxillofacial

surgery [5, 6]. Our experience with the use of resorbable

plates and screws in the surgery of craniosynostosis and

complex skull defects in children led to the idea of using

the same fixation technology for laminotomy.

Material and Methods

Resorbable plates and screws were used to fix

laminotomy flaps in 4 patients aged 4 to 11 years (at 3, 4,

5, and 9 levels). In total, the fixation was performed at 21

levels. The operations were performed for intradural

tumors and cysts of the spinal cord. The average time of

fixation was 15 minutes (which is approximately 2.5

times shorter than the duration of traditional fixation by

ligatures). There were no complications, flap

displacements or tissue reactions. The minimal follow up

period was 3 months.

Operation technique

In all cases laminotomy was performed after

subperiosteal dissection, following the procedure

described previously by the first author [1]. The intradural

stage of the surgery was performed using microsurgical

techniques and depended on a specific pathology. The

stage of fixing the flap began after tight sealing of the dura

mater. We used 1-mm thick plates with 4 holes in all

cases (the length and arrangement of holes was always

sufficient for our purpose) and pins with a diameter of 2.4

mm and a length of 5 mm. Plates were bent “in situ” to

produce the required configuration, just before they were

fixed. The fixation of all plates to the flap was carried out

immediately afterwards (Fig. 1).

Further, the flap was put in place and, if necessary,

the plates were additionally bent to ensure their optimal

contact with the base of the arches. Then most cranial

and caudal arches were fixed, which ensured correct

position of the flap in the wound. Finally, all the other

plates were fixed (Fig. 2). The wound was sutured layer

by layer in accordance with general surgical principles.

A schematic depiction of the method for fixing a

laminated bone flap is shown in Fig. 3.

Discussion

Literature search for use of resorbable plates and

screws in neurosurgery produced only results related to

cranial application [4, 6—8]. Therefore, it was not

possible to compare our experience with the literature

data. Nevertheless, it should be noted that resorbable

materials are gradually getting traction in traumatology,

orthopedics and spinal surgery and there are already

relevant publications. However, the main issues that are

discussed in these papers are mechanical strength and


ORIGINAL ARTICLES

reliability of fixation in comparison with metallic

analogs [5].

In our clinical study, this comparison is not

determinative. It is well known that the purpose of

laminotomy and fixation of the flap is not so much

immediate “stabilization” as restoration of the place of

fixation of the paraspinal musculature and prevention of

gross epidural fibrosis. In this situation, the main goal of

fixation is to position the flap “in situ”, where the

mechanical load on it is minimal, so even ligature fixation

is sufficient. We have been successfully using ligatures to

fix the laminotomy flaps since 2003 (more than 270

laminotomies were performed), and we have never noted

any issues related to insufficient rigidity of fixation or flap

displacement. The only significant drawback of this

technique is that it is labor-intense and time-consuming,

especially in case of laminotomies of more than 3 levels.

For example, the process of fixing a 5-level flap in the

thoracic spine can take up to 40 minutes. This procedure

becomes even more time-consuming in case of narrow

canal and thick arches. In addition, the process of drilling

holes in the roots of the arches often leads to additional

venous bleeding from the epidural veins, which also leads

to unnecessary waste of time and resources. The use of

resorbable plates is more promising in this situation. The

use of standard titanium plates in children is less desirable

for reasons we have already mentioned above: difficulty

in achieving good fixation of screws in thin and soft

arches of children’s vertebrae and issues with

relaminotomy in the event of relapse of the disease. In

addition, the classical technology of drilling holes and

tightening the screws does not provide any benefits in

terms of technology or convenience (in a narrow and

deep wound it is even more difficult) than imposing

ligatures.

Therefore, we became interested in resorbable plates

with ultrasonic “welding” of “screws”. Our preliminary

experience with the use of resorbable plates and pins was

positive. This technology provides reliable and fast

fixation for fixing a laminotomy flap. In addition, by

bending the plates in a specific manner, one can slightly

increase the transverse dimension of the spinal canal to

ensure decompression. The biggest drawback and the

main obstacle to the wide application of the described

technology, are the price of implantable products and

special equipment required for their installation.

Conclusion

The paper presents the initial experience of using

resorbable plates and pins (screws) for fixing a laminotomy

flap. We describe the surgical technique and provide

comparative evaluation of the proposed technology with

those already commonly used in practice.

The local ethical committee of the Burdenko

Neurosurgical Institute of the Ministry of Health of the

Russian Federation at the meeting of 09.06.16 (protocol

No 06/2016) approved the publication of this paper in a

specialized medical journal.


Fig. 1. Laminotomy flap with fixed plates.

Fig. 2. Laminotomy flap fixed in place.

Fig. 3. Scheme of the flap fixation. a — sagittal projection; b — frontal projection; c — general view in three

projections. 1 — laminotomy flap, fixed in its place; 2 — resorbable pins (screws);

3 — resorbable plates.


REFERENCES1. Kuschel YV. The role of laminotomy and laminoplasty in reducing the

frequency of post-operative kyphoscoliosis in children operated on for

intramedullary tumors. Problems of neurosurgery named after N.N. Burdenko. 2007;20-24..

2. Ruggeri A, Pichierri A, Marotta N, Tarantino R, Delfini R. Laminotomy in

adults: technique and results. Eur Spine J. 2012;21:364-372.

doi: 10.1007/s00586-011-1826-2

3. Kuschel YV. «Open-door» laminoplasty to remove common intramedullary

tumors in children — a new approach to intradural spinal pathology.

Problems of neurosurgery named after N.N. Burdenko. 2007;45-46.

4. Acosta HL, Stelnicki EJ, Rodriguez L, Slingbaum LA. Use of absorbable

poly (d,l) lactic acid plates in cranial-vault remodeling: presentation of the

first case and lessons learned about its use. Cleft Palate Craniofac J.

2005;42:333-339.

5. Vaccaro AR, Madigan L. Spinal applications of bioabsorbable implants. J Neurosurg. 2002;97:407-412.

6. Freudlsperger C, Castrillon-Oberndorfer G, Baechli H, Hoffmann J,

Mertens C, Engel M. The value of ultrasound-assisted pinned resorbable

osteosynthesis for cranial vault remodelling in craniosynostosis. J Cranio-maxillofac Surg. 2014;42:503-507.

7. Salokorpi N, Sinikumpu JJ, Iber T, Zibo HN, Areda T, Ylikontiola L, San-

dor GK, Serio W. Frontal cranial modeling using endocranial resorbable

plate fixation in 27 consecutive plagiocephaly and trigonocephaly patients.

Childs Nerv Syst. 2015;31:1121-1128.

8. Stendel R, Krischek B, Pietila TA. Biodegradable implants in neurosurgery.

Acta Neurochir (Wien). 2001;143:237-243.

This work is devoted to the use of resorbable plates and

pins for laminoplasty in children. The process described by the

authors was previously used only for cranioplasty, so its

application in spinal surgery is off-label.

The laminoplasty is widely used in treatment of cervical

spondylogenic myelopathy in Japan (Hirobayashi, Kurokava),

and in Russia (A.O. Guscha, O.A. Dreval). At present, there are

titanium plates of special shape for fixing the arches available

for carrying out this operation. Of course, the use of resorbable

products is an attractive alternative to metal ones, especially

when ultrasonic “welding” is used for fixing pins in place.

It remains unclear whether it is possible to use these

products in the elderly, given the frequency of laminoplasty in

the stenosis of the spinal canal at the cervical level and the

frequent sclerosis and fragility of the arches in this category of

patients.

A.O. Guscha (Moscow, Russia)

Commentary


ORIGINAL ARTICLES

doi: 10.17116/engneiro201680652-58

Minipterional Craniotomy in Surgery for Anterior Circle of Willis AneurysmsR.S. DZHINDZHIKHADZE, O.N. DREVAL’, V.A. LAZAREV, R.L. KAMBIEV

Russian Medical Academy of Postgraduate Education, Moscow, Russia; Inozemtsev City Clinical Hospital, Moscow, Russia

One of the significant events in aneurysm surgery was promotion of a microneurosurgical technique by G. Yasargil. Despite its versatility, pterional craniotomy is associated with extensive osteotomy and a significant incision of the skin and temporal muscle, which may lead to the adverse cosmetic effects, risk of temporomandibular joint dysfunction, injury to the frontal branch of the facial nerve, and facial and scalp numbness. We present our experience with minipterional craniotomy in surgery for anterior circle of Willis aneurysms in 40 patients. There were no serious complications or deaths. Also, there were no intraoperative aneurysm ruptures. All patients experienced expected transient hypesthesia in the temporal region, which was not considered as a complication. In this case, hypesthesia was significantly milder compared to that in the classical pterional craniotomy. Patients assessed the postoperative cosmetic outcome as excellent.

Keywords: minipterional craniotomy, keyhole, minimally invasive surgery, aneurysms.


The traditional pterional approach in surgery of

cerebral aneurysms was proposed by G. Yasargil. The

approach includes an arcuate incision of the skin from

the tragus to the midline along the hairline, followed by

an extensive dissection of the temporal muscle and

craniotomy of the frontotemporal region [1, 2].

This classical extensive approach is often associated

with various postoperative complications, unsatisfactory

cosmetic results, prolonged stay of patients in a hospital,

and prolonged postoperative recovery at the outpatient

stage, which entails great economic costs. Later,

J. Hernesniemi et al. [3] modified pterional craniotomy

(PC) and proposed a lateral supraorbital approach that

differed (in the authors’ opinion) from PC by the

subfrontal trajectory facilitating an approach to the

parasellar space and causing less damage.

The modern concept of keyhole surgery involves

reducing the aggressiveness of surgery by minimizing a

surgical approach. Modified keyhole approaches were

initially proposed in surgery of anterior circulation

aneurysm and parasellar space-occupying lesions

[4―23]. We have used a differentiated approach for

surgical accesses and the concept of keyhole surgery for

anterior circulation aneurysms and anterior and middle

cranial fossa tumors since 2014.

In this work, we present the experience of using the

minipterional craniotomy (MPC) in surgery of anterior

circle of Willis aneurysms.


In the period between March 2014 and December

2015, 40 aneurysms were clipped using the minipterional

craniotomy. The aneurysm location was as follows: 30

middle cerebral artery (MCA) aneurysms, 7 internal

carotid artery (ICA) aneurysms in the area of the posterior

communicating artery orifice, and 3 ophthalmic

aneurysms. The male:female ratio was 1:2.5. The mean

age of patients was 53.7 years. Thirty patients had

unruptured aneurysms. Ten patients had subarachnoid

hemorrhage (SAH): 7 of these were operated on in the

acute period. The condition of these patients was assessed

using the Hunt―Hess scale, and the amount of SAH was

assessed using the Fisher scale. Four patients underwent

surgery in the early period. Three patients underwent

clipping in the long-term period. All patients had a

Hunt―Hess grade of I or II and Fisher grade 1 or 2 SAH.

Preoperatively, all patients underwent two-

dimensional and 3D-CT angiography. The surgical

approach was chosen after a thorough evaluation of the

anatomy of intracranial structures and aneurysms. All

aneurysms clipped using MPC were of small or medium

size, no more than 15 mm in diameter. In the case of

complex large and giant aneurysms, the method of choice

involved more extended approaches ranging from the

classical pterional craniotomy to the orbitozygomatic

approach and its different modifications. Also, we did

not consider MPC as an acceptable technique in patients

in a decompensated state (Hunt―Hess grade IV―V) as

well as in the case of massive subarachnoid hemorrhages

and large parenchymal hematomas accompanied by

brain edema and intracranial hypertension. Along with

clipping, most of the patients underwent extensive

decompressive trepanation.

Surgical technique

Surgery is performed under general anesthesia, with

the patient in a supine position with the head turned in

the opposite direction at an angle of 30―60°, depending

on the lesion location. The neck is maximally extended

to provide gravitational retraction of the frontal lobe

from the skull base and adequate venous drainage. A

4―5 cm arcuate incision of the skin and soft tissues is

performed in the temporal region, starting from the


zygomatic process, 1 cm anterior to the superficial

temporal artery, and to the hairline or not reaching the

superior temporal line (Fig. 1).

Next, the classical interfascial temporal muscle

dissection is performed, with the frontal branch of the

facial nerve being preserved. An incision of the temporal

fascia is performed by monopolar coagulation with

preservation of the myofascial cuff. After a subperiosteal

dissection, the temporal muscle is expanded by a small

retractor or reduced by hook tensioners. This enables full

exposure of the pterion area. A burr hole is placed

superior to the frontozygomatic suture. A craniotomy,

2―3 cm in size, includes the lateral sphenoid bone, a

portion of the frontal bone below the superior temporal

line, and a minimum portion of the temporal bone. Like

in the classical PC, the sphenoid crest is resected until

the meningo-orbital artery in the superior orbital fissure

is visualized (Fig. 2).

The dura mater (DM) is opened by a semi-oval

incision, with its base directed towards the pterion. The

intradural stage of surgery is performed under a

microscope (Fig. 3).

The subsequent technique depends on the aneurysm

location. In the case of MCA aneurysms, the Sylvian

fissure is dissected anteriorly to the superficial Sylvian

veins that should be preserved from damage. The Sylvian

fissure is sharply dissected. Usually, small bridging veins

coming from the temporal lobe to the frontal lobe can be

coagulated without consequences. Of great importance is

a dissection in the subarachnoid space area to preserve

the cortex and minimize its damage. However, this is not

always possible in patients after massive subarachnoid

hemorrhage accompanied by brain edema and

obliteration of the Sylvian fissure. In the case of MCA

M1 bifurcation aneurysms, the transsylvian approach,

without dissection of the parasellar cisterns, may be

sufficient. In this situation, identification of the M1

segment to provide proximal control is the priority, and

then, the MCA branches (M2 segment) and aneurysms

are identified. After dissection, the aneurysm is clipped

with temporary clipping or without it. In the case of ICA

aneurysms, the classical microsurgical technique with

early brain relaxation by opening of the optic nerve and

carotid artery cisterns is used. Further, a limited

dissection of the medial Sylvian fissure is performed to

provide moderate traction of the frontal lobe and

visualization of the ICA bifurcation. The posterior

communicating artery is visualized through the optic-

carotid triangle. Arachnoid adhesions of the ICA are

sharply dissected, and then the anterior choroid artery is

identified. The microsurgical technique is dictated by the

aneurysm location. In the case of carotid-ophthalmic

aneurysms, intradural resection of the anterior clinoid

process may be necessary to provide proximal control

and visualization of the ophthalmic artery.

In the case of adequate brain relaxation after draining

the cerebrospinal fluid from the subarachnoid cisterns

and/or after pharmacological exposures, there is no need

for significant retraction of the parenchyma. In the case

of hemorrhage, the brain may be edematous. In these

cases, the carotid cistern is first opened for adequate

relaxation, which then enables more comfortable and

less traumatic dissection of the Sylvian fissure. Early

placement of a lumbar drain may be an alternative in

SAH patients.

After clipping the aneurysm and verifying its

complete exclusion (it is optimal to use intraoperative

indocyanine green (ICG) angiography, followed by

opening of the aneurysm), hemostasis is performed. The

DM is tightly closed. A bone flap is fixed with craniofixes

or miniplates. The temporal fascia/muscle, subcutaneous

tissue, and skin are sutured in layers (Fig. 4). Given a

small wound size, wound drainage is not performed,

which is also an undoubted advantage of minimally

invasive surgery.

Below, we provide an example of surgery in a female

patient with a carotid-ophthalmic ICA aneurysm. The

microsurgical stage of surgery was performed without

retractors (Fig. 5).

Results and discussion

All aneurysms were completely excluded from the

cerebral circulation, which was confirmed by

Fig. 1. A skin incision (solid line) for minipterional craniotomy. The dotted line indicates an incision for classical pterional craniotomy.

a

b


ORIGINAL ARTICLES

intraoperative opening of aneurysms and subsequent

monitoring using intraoperative indocyanine green

angiography and control 3D-SCT angiography in the

postoperative period. There were no serious complications

or lethal cases in patients. Also, there were no

intraoperative aneurysm ruptures. All patients

experienced transient hypesthesia in the temporal region,

which was expected and, therefore, was not regarded as a

complication. It should be noted, that the hypesthesia

area was significantly smaller when compared to the

outcomes of classical pterional craniotomy.

Fig. 2. Minimal pterional craniotomy.a ― an intraoperative view: a skin-aponeurotic flap is moved anteriorly, and the temporal muscle is spread by a retractor; b ― the size of a bone flap.

a b

Fig. 3. Stages of microsurgical treatment of a left MCA aneurysm.a ― SCT-angiography: a saccular aneurysm of the left MCA M1 segment is seen; b ― an intraoperative view after minipterional craniotomy and opening of the DM;

the center of craniotomy is situated over the Sylvian fissure; c, d ― stages of Sylvian fissure dissection; e ― the saccular aneurysm of the MCA M1 segment; f ―

clipping of the aneurysm; g, h ― intraoperative indocyanine green angiography: the aneurysm is excluded from blood flow, the MCA branches, not stenotic, are

visualized; i ― a view after clipping of the aneurysm and opening of the aneurysmal sac.


Patients assessed the postoperative cosmetic result as

excellent. In 2 patients, a follow-up examination at up to

10 months revealed minimal dysfunction in the

temporomandibular joint area and symptoms of temporal

muscle atrophy in the craniotomy area.

The traditional approach in surgery for intracranial

aneurysms of the anterior circulation is the pterional

craniotomy proposed by M. Yasargil in 1975 [1, 2].

Pterional craniotomy is associated with a quite extensive

osteotomy and a significant incision of the skin and

temporal muscle, which may lead to the following side

effects: temporal muscle atrophy, scar formation, facial

asymmetry, risk of temporomandibular joint dysfunction,

chewing pain, discomfort when wearing glasses, damage

to the frontal branch of the facial nerve, scalp numbness,

and scar alopecia. Exposure of the cortex at the intradural

stage, more significant in size, may be accompanied

by damage to the cortex due to the influence

of the non-physiological environment, retractor

trauma, etc [21―25].

The concept of keyhole is not new. Since its

introduction by A. Perneczky et al. [10, 11, 21―25],

considerable experience in surgery of aneurysms and

intracranial tumors has been accumulated. Keyhole

surgery is a modern concept that significantly reduces

injury caused by surgery. The size of keyhole craniotomy

is 2―3 cm, on average. However, this is not just a

reduction in the trephination window size. Keyhole

means the creation of an optimal surgical corridor in

each particular case to access a certain lesion with

minimal injury to both soft tissues, including the temporal

muscle, and brain tissue. This goal is achieved through

the use of small incisions of soft tissues, minimal DM

opening, and exposure of the cortex with minimal

retraction of the brain. This enables achieving the main

goals of minimally invasive neurosurgery: minimization

of surgical invasion, improvement of the cosmetic effect

compared to that of classical surgery, shorter surgery

time, reduction in blood loss, postoperative pain, and

postoperative complications, and shorter total hospital

stay, which reduces financial and economic costs for

treatment of patients. It is also important to assess the

outcomes of minimally invasive microsurgery of

aneurysms in terms of patient satisfaction with surgery.

The keyhole approaches used for anterior circulation

aneurysms are primarily supraorbital and minipterional

ones. B. Chehrazi [6] was one of the first researchers who

described a temporal transsylvian approach to aneurysms

as an alternative to the classical pterional craniotomy,

which was accompanied by a decrease in the trephination

Fig. 4. The wound closure stage.a ― a bone flap is put in place and fixed; b ― sutures on the skin; c, d, e ― control craniography and CT.


ORIGINAL ARTICLES

window. Later, many authors [5―16] used the mini-

invasive approach in aneurysm surgery, calling it a

modified pterional craniotomy. E. Figueiredo et al. [10,

11] compared the minipterional approach and the

pterional craniotomy in two groups of patients. Despite

the similar treatment outcomes, the authors noted that

the minipterional approach was associated with less

damage to soft tissues and less craniotomy, which

reduced the time of surgery and recovery period and

improved cosmetic results. A necessary support in

keyhole surgery of aneurysms is the use of an additional

imaging technique, intraoperative indocyanine green

fluorescence angiography [4, 26―28].

Keyhole surgery is based on a thorough preoperative

assessment to determine the trephination window

position depending on the pathological process and

individual patho-anatomic picture. We associate the

good results of surgical treatment in our group with

careful preoperative selection of candidates for minimally

invasive surgery and exclusion of patients being at the

decompensated stage (Hunt―Hess grade IV―V).

Patients with unruptured aneurysms are ideal candidates

for keyhole surgery, except for patients with large and

giant aneurysms. Among patients with the clinical

presentation of SAH, the most favorable candidates for

minimally invasive surgery are patients with Hunt―Hess

grade I―II aneurysms. For subcompensated and

decompensated patients, we consider the classical

pterional approach with its modifications (orbitopterional

or orbitozygomatic craniotomy) as the method of choice.

Fig. 5. Stages of microsurgical treatment of a carotid-ophthalmic ICA aneurysm.a ― SCT-angiography: a carotid-ophthalmic aneurysm on the right is visualized; b ― an intraoperative image after minipterional craniotomy and opening of the

DM; the Sylvian fissure is indicated by the arrow; c ― intradural resection of the anterior clinoid process by a 2 mm diamond burr; d, e ― stages of aneurysm

isolation; f ― aneurysm clipping; g ― a view of the surgical wound at the end of surgery.


Conclusion

The minipterional craniotomy is the method of

choice for most MCA and some ICA aneurysms. The

main goal of keyhole surgery is not only to reduce the

trephination window but also to decrease traction brain

injury. An important support in minimally invasive

14. Mori K, Osada H, Yamamoto T, Nakao Y, Maeda M. Pterional keyhole

approach to middle cerebral artery aneurysms through an outer canthal skin

incision. Minim Invas Neurosurg. 2007;50:195-201.

doi: 10.1055/s-2007-985837

15. Mori K, Esaki T, Yamamoto T, Nakao Y. Individualized pterional keyhole

clipping surgery based on a preoperative threedimensional virtual osteoto-

my technique for unruptured middle cerebral artery aneurysm. Minim Invas Neurosurg. 2011;54:207-213.

doi: 10.1055/s-0031-1286335

16. Nathal E, Gomez-Amador JL. Anatomic and surgical basis of the sphenoid

ridge keyhole approach for cerebral aneurysms. Neurosurgery.

2005;56:ONS178-ONS185.

doi: 10.1227/01.NEU.0000145967.66852.96

17. Paladino J, Mrak G, Miklic P, Jednacak H, Mihaljevic D. The keyhole con-

cept in aneurysm surgery − a comparative study: keyhole versus standard

craniotomy. Minim Invas Neurosurg. 2005;48:251-258.

doi: 10.1055/s-2005-915599

18. Park J, Kang DH, Chun BY. Supercilicary keyhole surgery for unruptured

posterior communicating artery aneurysms with oculomotor nerve palsy:

maximizing symptomatic resolution and minimizing surgical invasiveness. J Neurosurg. 2011;115:700-706.

doi: 10.3171/2011.5.jns102087

19. Park J, Woo H, Kang DH, Sung JK, Kim Y. Superciliary keyhole approach

for small unruptured aneurysms in anterior cerebral circulation. Neurosur-gery. 2011;68:оns300-ons309.

doi: 10.1227/neu.0b013e3182124810

20. Perneczky A, Tschabitscher M, Resch KDM. Endoscopic anatomy for neu-rosurgery. New York: Thieme. 1993.

21. Perneczky A, Muller-Forell W, van Lindert E, Fries G. Keyhole concept in

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surgery of aneurysms is the use of ICG-angiography and

endoscopic assistance, which greatly enhances

visualization and control in a narrow deep wound.

.



ORIGINAL ARTICLES

Pterional craniotomy with transsylvian dissection provides

a wide viewing angle for manipulations with intracranial

structures and is used as a standard approach for clipping of

anterior circulation and upper basilar artery aneurysms. A

modification of the pterional craniotomy in terms of mini-

invasive surgery, called minipterional craniotomy, is

characterized by reduced iatrogenic trauma. High safety of

surgery is achieved by reducing the length of a skin incision,

length of temporal muscle dissection, size of a bone flap, and

time spent on performing the approach and closing the wound.

Any desire to minimize a surgical approach to intracranial

structures requires a comparative evaluation of the safety of the

new technique, degree of its versatility (applicability), duration

of surgery, cosmetic results, etc. In the presented work, R.S.

Dzhindzhikhadze and co-authors analyze the experience of

using minipterional craniotomy in treatment of 40 saccular

aneurysms of the carotid territory, with 30 of them being middle

cerebral artery aneurysms.

In the discussion of minimally invasive approaches in

surgery of aneurysms, the authors refer to studies devoted to a

supraciliary approach. The supraciliary approach is a variant of

the supraorbital subfrontal approach and, being significantly

different, provides significantly less freedom of surgical

manipilations in the Sylvian fissure compared to the

minipterional approach.

The indications for minimally invasive surgery, including

minipterional craniotomy, in treatment of arterial aneurysms

are determined not only by the aneurysm size but also by the

aneurysm neck configuration. The use of a relatively narrow

intracranial corridor reduces visualization and hampers

arachnoid dissection of the vascular structures as well as limits

the use of complex configuration clips and clip holders with

large swing flexible heads.

Commentary

The minipterional approach is most appropriate for

clipping of middle cerebral artery and supraclinoid internal

carotid artery aneurysms with a simple neck configuration

directed perpendicular to the axis of a planned approach.

Exposure of the Sylvian fissure within a relatively small

trephination window enables its safe dissection in the

lateromedial (distal-proximal) direction, which is usually

sufficient for clipping of middle cerebral artery aneurysms. In

my opinion, this approach can not be used for complex middle

cerebral artery and anterior communicating artery aneurysms

and, if necessary, for contralateral dissection in multiple

aneurysms. All similar cases require extensive arachnoid

dissection with retraction of the frontal lobe and the standard

pterional craniotomy, the size of which enables insertion of

instruments and clips into the depth of the wound at different

angles.

The presented good results of minipterional craniotomy in

surgical treatment of aneurysms of the carotid territory are

associated with careful analysis of the relationship among the

aneurysm location, the direction and shape of the aneurysm

neck, the presence of hemorrhages and edema of brain tissue

that have been considered by the authors at the preoperative

planning stage. Experience of R.S. Dzhindzhikhadze and co-

authors emphasizes the important point about the need for

selecting not only a surgical approach but also its minimally

invasive modification to ensure both the primary goal of surgical

intervention (safe clipping of the aneurysm) and reduce the

total injury rate and duration of surgery.

Yu.A. Grigoryan (Moscow, Russia)


doi: 10.17116/engneiro201680659-66

A Giant Hyperostotic Parasagittal Meningioma in a Child with Neurofibromatosis Type II. A Case Report and Literature ReviewA.N. SAVATEEV, A.N. KONOVALOV, S.K. GORELYSHEV, L.A. SATANIN, E.A. KHUKHLAEVA, L.V. SHISHKINA, V.I. OZEROVA, E.F. VALIAKHMETOVA, O.A. MEDVEDEVA


Large parasagittal meningiomas, in particular hyperostotic ones, in children are rare and problematic in the differential diagnosis. The literature reports only single clinical cases related to this issue; opinions about the indications, surgical treatment options, and prognosis are contradictory. This paper presents a clinical case of a hyperostotic parasagittal meningioma with intra- and extracranial growth in a 10-year-old boy with neurofibromatosis type II, which significantly worsened the prognosis. We discuss the epidemiological and clinical features of childhood meningiomas and issues of their diagnosis, treatment, and prognosis.

Keywords: parasagittal, meningioma, hyperostosis, children, neurofibromatosis.

e-mail: [email protected] © Group of authors, 2016

Meningiomas diagnosed in children under the age of

15 years form a special group and have a number of

principal differences from meningiomas in adults.

Parasagittal meningiomas are less common in children

than in adults and account for only 4% of all brain tumors

[1]. Hyperostosis can occur in association with convexity

and parasagittal meningiomas [2]. In childhood,

25―49% of meningiomas are associated with

hyperostosis [3―6], while in adults, this figure amounts

to 4.5% [2]. In children, 33―40% of meningiomas are

associated with neurofibromatosis type II (NF-2) [3,

6―8], which is a factor worsening the disease prognosis

[1, 3, 9].

In this article, we present a rare clinical case of

hyperostosis associated with a giant parasagittal

meningioma with intra- and extracranial growth in a

child with NF-2.

Clinical case

A 10-year-old boy L. applied to the Neurosurgical

Institute (August 31, 2015) with complaints of a bulging

in the parietal region. Eleven days before hospitalization,

the patient had acutely developed right-sided hemiparesis

and hemihypesthesia that completely regressed within 8

days of conservative treatment, including osmodiuretics

and glucocorticoids. Careful taking of a family history

Abbreviations

VEGF ― vascular endothelial growth factor

DFS ― disease-free survival

ICA ― internal carotid artery

SSS ― superior sagittal sinus

Gr ― Gray

MRI ― magnetic resonance imaging

ECA ― external carotid artery

NF-2 ― neurofibromatosis type II

SCT ― spiral computed tomography

DМ ― dura mater

revealed that the child’s grandmother had bilateral

neurinomas of the vestibulocochlear nerve (absolute

diagnostic criterion for NF-2 [10]), and his mother died

of an unspecified brain tumor (she refused surgery, so

there was no histological verification). MRI of the brain

detected a large parasagittal tumor with intra- and

extracranial growth, perifocal edema, and involvement

of the parietal bones, which invaded the middle third of

the superior sagittal sinus (Fig. 1).

At admission, there were no focal neurological and

intracranial hypertension symptoms. The Karnofsky

scale score was 100. On examination, a tight elastic

bulging in the temporal parasagittal region, mostly on the

left, was found. The time of its emergence was unknown.

No subcutaneous neurofibromas were found. SCT of the

brain revealed a parasagittal contrast enhanced tumor as

well as a hyperostotic lesion of both parietal bones,

11×8.5 cm in size, with a marked periosteal reaction

(Fig. 2). According to total selective cerebral angiography,

the afferents feeding the tumor were multiple small

branches of the ICA and ECA; the superior sagittal sinus

was not enhanced at the tumor site (Fig. 3).

Given the history, examination, and radiographic

findings, including intra- and extracranial components

of the tumor and the bone lesion, the diagnosis was

CASE REPORTS


CASE REPORTS

differentiated between primary Ewing’s sarcoma of the

parietal bone and hyperostotic parasagittal meningioma.

To determine the tactics of treatment, an open

biopsy of the extracranial portion of the tumor was

performed (03.09.15). The biopsy revealed

meningotheliomatous meningioma, WHO Grade I, with

a Ki-67 labeling index of 5―7%. An attempt to resect the

tumor was made (10.09.15). Resection of the extracranial

tumor component and resection trepanation of the skull

with removal of hyperostosis were performed through a

horseshoe-shaped skin incision in the projection of the

affected calvarial area. This procedure exposed the

intracranial tumor portion, but surgery was terminated

due to a high blood loss and a high risk of further massive

bleeding. At the second stage, 8 days later, the intracranial

tumor portion was removed. The superior sagittal sinus

walls occurred to be the initial site of tumor growth.

Because of marked venous bleeding from the sagittal

sinus, a drop in arterial pressure, and the risk of

impairment of venous outflow from large vessels of the

parietal region, total removal with resection of the ICA

was not performed. The ICA wall was strengthened with

tachocomb and artificial DM. The extent of tumor

resection was Simpson grade 4 [11]. According to the

pathology report, the resected intracranial meningioma

portion was identified as atypical meningioma, WHO

Grade II. On September 23, 2015, the patient underwent

duraplasty (artificial sheath) and bone defect

reconstruction using Palakos (Fig. 4). The patient was

discharged home 2 weeks after surgery. By that time, the

child was active, walked around the department, played,

communicated with others, and was capable of self care.

The Karnofsky scale score was 100.

One month later, control MRI of the brain revealed

small residuals of the meningioma in the superior sagittal

sinus region (Fig. 5). Given the family history, MRI of all

parts of the spinal cord was also performed, which

revealed a space-occupying lesion at the C6―C7 space

level on the left, most likely neurinoma, which did not

clinically manifest itself (Fig. 5, 6). Thus, the child had a

combination of the intracranial meningioma, neurinoma

of the C6―C7 spinal nerve, and family history (a direct

relative with NF-2), which was the basis to diagnose

neurofibromatosis type II.

Three months after tumor resection, the patient

underwent a course of stereotactic radiation therapy at a

dose of 60 Gy in 30 fractions for the residual meningioma.

Control MRI of the brain at 6 and 12 months after surgery

did not detect continued growth. Further radiation

treatment for the neurinoma at the C6―C7 level was

under discussion.

Discussion

The annual incidence rate of meningiomas increases

with age and peaks at 8.4 per 100,000 population by the

eighth decade of life [12]. Meningiomas account for

13―25% of all adult intracranial tumors [13]. At the

same time, the occurrence of these tumors in children is

much lower and is only 0.4―4.6% [1, 3, 14]. Adult

meningiomas are more common in females [9, 12]; on

the contrary, pediatric meningiomas are more common

in boys [1]. However, according to some studies [4], the

primary incidence of meningiomas is approximately the

same in children of both genders. Pediatric meningiomas

are associated with hyperostosis in 25―49% of cases

[3―6], while this parameter is 4.5% for adult tumors [2].

The topography of pediatric and adult meningiomas

is also different. Convexity meningiomas account for

41% of pediatric meningiomas [1] and only 19% of adult

Fig. 1. Preoperative MRI scans of the 10-year-old patient L. Extra- and intracranial components of a space-occupying lesion and a parietal bone lesion are seen.


meningiomas [15]. Parasagittal pediatric meningiomas

are rare (about 4% of cases [1]) in contrast to adult tumors

(25% of cases [15]). In addition, pediatric meningiomas

are often (about 15% of cases) found in the ventricle

cavity [1, 4].

Y. Liu et al. [1] (2008) analyzed a large number of

pediatric meningiomas and concluded that the prognosis

was primarily affected by the following factors: the extent

of initial resection (total resection is associated with a

better prognosis), location of the tumor (affects the

completeness of resection and, indirectly, the prognosis),

presence of NF-2, and previous radiation treatment for

other tumors (worsens the prognosis). In 33―40% of

cases, pediatric meningiomas are associated with

neurofibromatosis type II [3, 6―8]. Neurofibromatosis

type II is believed to increase the risk of recurrence and

death in meningiomas [1, 3, 9, 16]. At the same time, the

degree of anaplasia is a less significant factor [1].

Bilateral neurinomas of the VIIIth nerve are the

absolute diagnostic criteria for NF-2 [10, 17]. Also, the

diagnosis of NF-2 is established if there is a direct relative

having this disease in a combination with either unilateral

neurinoma of the VIIIth nerve or two or more of the

following signs: neurofibroma, meningioma (one or

more), glioma (one or more), schwannomas (including

one or more spinal schwannomas), and juvenile posterior

subcapsular lenticular cataract [10, 17]. Cafe-au-lait

spots occur in approximately 80% of NF-2 patients but

have no diagnostic significance [10].

The main method to diagnose meningiomas is MRI.

Meningiomas sometimes invade vital vascular structures,

so direct selective cerebral angiography is an important

Fig. 2. Preoperative SCT images of the 10-year-old patient L. Periosteal hyperostosis of both parietal bones and an irregular surface of the affected bone are presented.

Fig. 3. Angiography of the 10-year-old patient L. The afferents are small branches of the ICA and ECA. The superior sagittal sinus is not enhanced in the tumor area.


CASE REPORTS

adjunctive diagnostic technique in the preoperative

period. In addition, in the presence of large feeding

vessels, the vessels can be embolized to reduce blood loss

at the main stage of treatment [3, 18].

As early as 1987, K. Kim et al. [19] emphasized the

importance of spiral computed tomography for the

diagnosis of tumors associated with hyperostosis. The

authors noted that hyperostosis associated with convexity

or sphenoid wing meningiomas may often be confused

with bone changes associated with other pathological

processes, such as fibrous dysplasia, osteoma, or sarcoma.

All 9 cases presented in the study had one or more CT

features typical of hyperostosing meningiomas, namely:

a pronounced periosteal reaction, inward bulging of the

bone in the lesion area, an irregular eroded surface of the

affected bone, and intracranial changes. The authors [19]

argue that high-resolution computed tomography is the

method of choice for evaluation of hyperostosis and

differential diagnosis of hyperostosing meningiomas and

other diseases. The literature [18, 20, 21] reports only

single cases of meningiomas associated with hyperostosis

in children. The presented clinical case is rare and of

great interest because of the medical history features and

the complexity of differential diagnosis. Before the tumor

biopsy, one of the presumptive diagnoses was a

meningioma in the setting of neurofibromatosis type II.

However, the patient did not fully meet the diagnostic

criteria: having a direct relative with bilateral neurinomas

of the VIIIth nerve, the patient himself had a single tumor

and no neurinomas by the time of hospitalization. A giant

meningioma in the child without neurofibromatosis was

unlikely. MRI and CT findings might equally indicate

hyperostosing meningioma and Ewing’s sarcoma.

Therefore, the second potential diagnosis was primary

Ewing’s sarcoma of the cranial vault. This diagnosis was

favored by a short history of just 11 days after the onset of

symptoms and location of the tumor ― the parietal and

frontal regions that are typical primary sites of Ewing’s

sarcoma growth [22]. In addition, bone changes

associated with this tumor can be characterized either by

lysis of the inner and outer bone plates or by sclerosis of

bone tissue with a periosteal reaction in the form of

spicules, which is hardly distinguishable from hyperostosis

in meningioma on CT images.

In the world practice, both tumor resection and

neoadjuvant chemotherapy are used as the primary

treatment for Ewing’s sarcoma [22―25]. Chemotherapy

can be selected as primary treatment in the absence of

symptoms of intracranial hypertension [25]; in our case,

there was no intracranial hypertension. If treatment starts

with chemotherapy, the 5-, 10-, 15-, and 20-year overall

Fig. 4. A CT image of the 10-year-old patient L. after duraplasty and bone defect reconstruction.

Fig. 5. Postoperative MRI scans of the 10-year-old patient L. Tumor residuals in the sagittal sinus area are indicated by arrows.


survival of patients with Ewing’s sarcoma is 57.2, 49.3,

44.9, and 38.4%, respectively [26].

The standard of treatment for meningiomas is

surgical resection. However, total resection is achieved

only in 80―90% of patients [3]. The surgeon should

strive for total resection of convexity and olfactory

meningiomas as well as meningiomas of the anterior

third of the cerebral falx and the superior sagittal sinus.

Fig. 6. MRI scans of all parts of the spinal cord of the 10-year-old patient L. A neurinoma at the C6―C7 level on the left is indicated by arrows.


CASE REPORTS

At the same time, if the tumor is located in the medial

sphenoid wings, posterior superior sagittal sinus, clivus,

or orbit, subtotal resection is safer treatment [18, 27].

Based on these factors and the diagnosis, a treatment

approach is chosen. After an open biopsy and receiving

the results of a histological study, the diagnosis and the

need in maximally radical surgery became apparent.

According to the literature [28], adjuvant radiation

therapy significantly improves local tumor control in

atypical and malignant meningiomas, especially in cases

of subtotal resection. Despite the fact that the difference

in disease-free survival after surgical and combined

treatment of meningiomas was not statistically significant

in most studies [28], some authors have still found a

significant difference confirming the positive effect of

radiotherapy on disease-free survival [29]. For example,

I. Piscevic et al. [29] (2015) reported the following results:

out of 88 meningioma patients, 58 patients had recurrence

within a mean follow-up period of 5.6 years. Five-year

disease-free survival (DFS) in patients who underwent

tumor resection followed by radiotherapy at a dose of

55/60 Gy (n=34) was 65%, and that in patients who

underwent surgery alone (n=24) was 13%. The differences

were statistically significant (Log rank=31.9; p=0.001).

For atypical meningiomas, the DFS difference was even

more significant (Log rank=34.1; p=0.001): the 5-year

DFS in combined and surgical treatment groups was 75

and 12%, respectively. It should be noted that the

literature lacks studies devoted to the efficacy and safety

of radiation therapy in pediatric meningiomas, and

patients with neurofibromatosis have been excluded from

most similar studies.

Unlike patients with sporadic tumors, patients with

NF-2 often have multiple or extensive tumors and a high

risk of recurrence [1, 3, 9, 16], which in some cases limits

the capabilities of surgery and radiotherapy.

Pharmacological therapy with proven efficacy in

meningiomas is currently not available. However, a

better understanding of the molecular mechanisms of

NF-2 pathogenesis opens the opportunity for application

of targeted therapy.

Tumor growth is often accompanied by

neovascularization, therefore tumors produce angiogenic

factors, such as the vascular endothelial growth factor

(VEGF) [30]. A VEGF inhibitor is the medication

bevacizumab [30]. This is a humanized monoclonal

antibody that prevents binding of all VEGF isoforms to

VEGF receptors. A study by F. Nunes et al. [31] (2013),

which evaluated a meningioma response to bevacizumab

treatment in NF-2 patients, demonstrated that a partial

response (a decrease in the tumor size by more than 20%)

was received in 30% of the patients. A gradual decrease in

the tumor in patients on treatment lasted for 3.7 months,

on average, and then the size remained stable. The mean

duration of remission was 15 months.

Despite the fact that bevacizumab is effective only in

a third of patients, targeted therapy may be used in

meningioma patients in the setting of NF-2 if other anti-

recurrence treatments fail.

Conclusion

In the presented case, the cause to use staged surgery

was poorly controlled bleeding at all stages of soft tissue

manipulations and tumor resection, which may lead to a

significant blood loss and serious complications. The

staged surgical treatment enabled resection of the extra-

and intracranial tumor portions, followed by

reconstructive closure of the bone defect without negative

somatic and neurological effects, as well as good and

rapid functional recovery of the patient.

In conclusion, it is necessary to emphasize the

importance of a careful taking of family and hereditary

history as well as MRI of not only the head but all parts of

the spinal cord in children operated on for meningiomas.

In the presented case, this facilitated identification of an

asymptomatic neurinoma at the cervical level,

establishment of the diagnosis of NF-2 (negatively

affecting the prognosis), and adjustment of the treatment.


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20. Cataltepe O, Ekin Ozcan O, Sagmanli S, Onol B. A giant hyperostosing

meningioma in a child. Neurochirurgia (Stuttg). 1992;35(5):171-175.

21. Wald U, Zagzag D, Umansky F, Rosen LM. Hyperostotic meningioma pre-

senting as an asymptomatic forehead bulge in a 7-year-old girl. Eur J Pedi-atr. 1985;144(4):419-420.

22. Boumdin H, el Quessar A, Chakir N, el Hassani MR, Jiddane M. Primary

Ewing’s sarcoma of the cranial vault. Report of 2 cases. J Neuroradiol. 2001;28(3):200-204.

23. Bhatoe HS, Deshpande GU. Primary cranial Ewing’s sarcoma. Br J Neuro-surg. 1998;12(2):165-169.

24. Moschovi M, Alexiou GA, Tourkantoni N, Balafouta ME, Antypas C,

Tsiotra M, Sfakianos G, Prodromou N. Cranial Ewing’s sarcoma in chil-

dren. Neurol Sci. 2011;32(4):691-694.

25. Salunke PS, Gupta K, Malik V, Kumar N, Henke LE, Cai C, Chen WS,

Pfeifer JD. Primary Ewing’s sarcoma of cranial bones: analysis of ten pa-

tients. Acta Neurochir (Wien). 2011;153(7):1477-1485.

26. Bacci G, Forni C, Longhi A, Ferrari S, Donati D, De Paolis M, Barbieri E,

Pignotti E, Rosito P, Versari M. Long-term outcome for patients with non-

metastatic Ewing’s sarcoma treated with adjuvant and neoadjuvant chemo-

therapies. 402 patients treated at Rizzoli between 1972 and 1992. Eur J Can-cer. 2004;40(1):73-83.

27. Bonnal J, Thibaut A, Brotchi J, Born J. Invading meningiomas of the sphe-

noid ridge. J Neurosurg. 1980;53(5):587-599.

28. Kaur G, Sayegh ET, Larson A, Bloch O, Madden M, Sun MZ, Barani IJ,

James CD, Parsa AT. Adjuvant radiotherapy for atypical and malignant me-

ningiomas: a systematic review. Neuro Oncol. 2014;16(5):628-636.

29. Pisćević I, Villa A, Milićević M, Ilić R, Nikitović M, Cavallo LM, Grujičić

D. The Influence of Adjuvant Radiotherapy in Atypical and Anaplastic Me-

ningiomas: A Series of 88 Patients in a Single Institution. World Neurosurg.

2015;83(6):987-995.

30. Kholodov BV, Abdullaev RT, Tarasova EM, Gorelyshev SK, Shishkina LV,

Zheludkova OG, Klimchuk OV, Shcherbenko OI, Prityko AG. The use of

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PLoS One. 2013;8(3):e59941.

Commentary

The paper describes and discusses a rare clinical case that is

also of great theoretical importance. The work is easy to read

and well illustrated. The discussion of the case and comparison

with the literature data provide the reader with an adequate

view of the issue and the current state of the problem. The

article is of great interest to a wide range of neurooncologists

and neuropediatricians.

V.A. Khachatryan (Saint Petersburg, Russia)


CASE REPORTS

Commentary

The presented observation is a rare case of neurofibromatosis

type II combined with parasagittal meningioma in a child and is

devoted to solving topical issues of neurosurgery, in particular,

modern treatment options for primary brain tumors. This

problem is important for several reasons related to improvement

of diagnostic methods, new capabilities of the modern

microneurosurgical complex, and an increase in the resectability

of this complex group of patients. Undoubtedly, surgery is

believed to be the main modern technique in complex treatment

is surgical, but the tactics of surgical treatment, choice of an

operative approach and methods that increase the radicalness

of tumor resection still remain controversial, which causes

increased interest in this clinical case and confirms the topicality

of the problem.

The tumor nature of hyperostosis in meningiomas is now

generally recognized. However, invasion of the dura mater and

bone by the tumor and formation of hyperostosis are not

considered as signs of biological aggressiveness, and hyperostosis

associated with parasagittal meningiomas has no effect on

recurrence. Only an increased number of recurrences in the

case of bone destruction or hyperostosis combined with

destruction have been observed. Head soft tissue invasion by

meningioma is considered as an indicator of biological

aggressiveness of the tumor.

The literature emphasizes a high recurrence rate of

parasagittal meningiomas, which is associated with anatomic

limitations of surgical radicalness in this area. Parasagittal

meningiomas affect the superior sagittal sinus in 15―50% of

cases, which sometimes objectively complicates one-stage

resection of the tumor. In these cases, surgery should be broken

up into several stages. Anatomical data should be considered

when planning and evaluating outcomes of surgical treatment.

The presented work provides a detailed, critical, and

chronological analysis of the literature data on neurofibromatosis

type II associated with meningiomas. The authors rightly put

emphasis on insufficiently resolved issues of this complex

pathology.

This clinical case is of considerable scientific and practical

interest and is devoted to the solution of topical issues of

neurosurgery and neurooncology. The work is well illustrated

and written in a good literary language and may serve as a guide

for both novice neurosurgeons and experienced specialists.

V.V. Timirgaz (Chisinau, Moldova)


doi: 10.17116/engneiro201680667-73

Spinal Stroke in a Pregnant Female with an Endodermal Cyst of the Cervical Spinal Cord (a Case Report and Literature Review)M.A. MARTYNOVA1, N.A. KONOVALOV1, A.YU. LUBNIN1, A.V. SHMIGEL’SKIY1, I.A. SAVIN1, T.F. TABASARANSKIY1, K.N. AKHVLEDIANI2, E.V. SINBUKHOVA1, R.A. ONOPRIENKO1

1Burdenko Neurosurgical Institute, Moscow, Russia; 2Moscow Regional Research Institute of obstetriics and Gynecology, Moscow, Russia

Objective. The study purpose was to present a clinical case of spinal stroke in a pregnant female, which was caused by an endodermal cyst of the cervical spinal cord, and to analyze treatment tactics.Results. A 20 week pregnant female presented with acute transverse spinal cord injury at the of C3―C5 spinal segment level. CT revealed an extramedullary space-occupying lesion in the ventrolateral position, with compression of the spinal cord at this level. The patient in the state of progressive deterioration with respiratory failure was transferred to the Neurosurgical Institute on the 5th day after disease onset. The patient underwent surgery on the 7th day after disease onset. Doctors of various specialties participated in preparation for surgery. During surgery, total resection of the space-occupying lesion and spinal cord decompression were performed. An obstetrician-gynecologist conducted intraoperative fetal monitoring by ultrasound. The histological diagnosis was an endodermal cyst. There was no improvement of neurological symptoms in the early postoperative period. After stabilization of the condition, the patient was discharged for follow-up care at the place of residence. According to the follow-up report, the patient underwent the cesarean section because of exacerbation of lung infection and a significant delay in the fetal development. After a few days, the patient died due to multiple organ failure. The child was alive, in serious condition, under mechanical ventilation.Conclusion. In the case of spinal stroke, the decision on treatment tactics should be made no later than 12 hours after its onset; otherwise, the outcome is usually unfavorable, and a neurological deficit is irreversible. The decision about continuing pregnancy should be made individually in each case, and an approach to the choice of appropriate treatment tactics should be multi-disciplinary.

Keywords: spinal stroke, extramedullary tumor, spinal cord tumor, endodermal cyst, pregnancy.

e-mail: [email protected]© Group of authors 2016

Spinal stroke, especially at the cervical level, poses a

serious danger to the patient’s life and health. In our

practice, we were faced with a similar situation where the

patient was a female with incomplete pregnancy. This

article discusses the experience in treatment of the patient

and associated problems.

Clinical case

A 24-year-old female patient M. was transferred

from a regional hospital at the place of residence to the

Burdenko Neurosurgical Institute (BNI). The patient

was at 20 weeks gestation.

According to a medical history, the patient suffered

from neck pain since the end of August 2015 and received

pain relievers. In the evening of September 05, 2015, she

noted numbness and growing weakness in the upper and

lower extremities. In the morning, she could not move

the extremities. The patient was transported by an

ambulance team to a regional hospital; after examination

by a neurologist and neurosurgeon, she was immediately

transferred to the Critical Care Department. The

patient’s condition at admission was evaluated as serious.

The patient was clearly conscious and complained of

neck pain, especially during head movements. Breathing

was spontaneous and adequate. Bilateral anesthesia of all

kinds of sensitivity, starting at the C3―C5 level of the

spinal cord, and flaccid tetraplegia were present. Reflexes

in the upper and lower extremities were absent. There

was acute urinary retention.

Within 1 day of hospitalization, the patient’s

condition began to deteriorate rapidly: respiratory failure

worsened, which required intubation of the trachea and

ventilation. On the second day of stay at the hospital,

after stabilization of the vital functions, the patient

underwent spiral computed tomography (SCT) of the

cervical spine, which revealed a space-occupying lesion

in the vertebral canal at the C3―C5 level, which was

located extramedullary and markedly compressed the

spinal cord (Fig. 1). Blood test indicators were without

significant abnormalities, except for hypokalemia

(3.0 mmol/L).

Ultrasound of the uterine cavity confirmed a

normally developing pregnancy at 20 weeks. There were

no obstetric indications for abortion.

On the 3rd day after the development of focal

symptoms, the patient was transferred to the BNI for

surgical treatment. The patient’s condition at admission

was serious: she was in the supine position in a passive

pose. Ventilation was performed through an orotracheal

tube. The patient followed simple instructions (she

answered simple questions by nodding of the head,

articulated, and closed the eyes on command) but quickly

exhausted; there were no movements in all the

extremities; there was a loss of all types of sensation,

starting at the C5―C6 level of the spinal cord and below.

The patient had hyperthermia of up to 38.7 °C and

arterial hypotension that required intravenous infusion of

vasopressors (norepinephrine), and worsening respiratory

failure (acceptable SpO2 figures were reached only at

FiO2=0.8). X-ray of the lungs revealed bilateral infiltrative

shadows in the lower lobes and perihilar portions. The

patient underwent therapeutic fibrobronchoscopy


CASE REPORTS

accompanied by removal of a small amount of viscous

purulent sputum. Given the episodes of desaturation and

desynchronization with the respirator, elevation of the

CRP level, fever, pulmonary radiographic findings,

nature of the underlying disease, and expected need for

prolonged ventilation, a puncture tracheostomy was

performed on the second day of stay at the Critical Care

Department of the BNI. On ventilation with positive end

expiratory pressure of 10 cm and FiO2=0.6 as well as

norepinephrine infusion, the patient’s condition was

stabilized, after which (on the 5th day of stay at the BNI),

she underwent magnetic resonance imaging (MRI) of

the cervical spinal cord (Fig. 2) and brain. MRI revealed

an extramedullary space-occupying lesion at the C3―

C5 level, which was located in the vertebral canal on the

right anteriorly, compressing the spinal cord and

displacing it to the left posteriorly. The lesion had a high

T2 signal (Fig. 2a, c), differing from that of free CSF, and

relatively clear smooth contours. T1-weighted MRI

revealed signs of parietal hemorrhage in the lesion

(Fig. 2b). The spinal cord at the pathology level and I or

II vertebra below it, as well as the medulla oblongata, had

signs of vasogenic edema. Series of T1 and T2-weighted

axial MRI scans of the brain revealed no pathological

changes.

The patient repeatedly consulted an obstetrician-

gynecologist and underwent daily ultrasound of the

uterine cavity, which revealed signs of threatened

miscarriage. There were no obstetric indications for

abortion. The patient was offered surgery for removal of

the space-occupying lesion at the C3―C5 level with

preserving pregnancy; the patient and her mother gave a

written consent.

On the 7th day of stay at the BNI, the patient

underwent surgery: microsurgical resection of the

extramedullary space-occupying lesion at the C3―C5

level using ultrasound monitoring of the fetus.

Anesthesia included intravenous propofol (infusion

under control of anesthesia depth) + intravenous bolus of

fentanyl and rocuronium during surgery. Arterial pressure

was monitored directly through a catheter placed in the

left radial artery. Continuous intravenous infusion of

norepinephrine was performed throughout surgery due

to the tendency to arterial hypotension.

The patient was placed in the left lateral position that

was considered as the most physiological one, given the

gestational age and the need for intraoperative ultrasound

monitoring of the fetus. The patient’s head was fixed with

a Mayfield clamp; the patient underwent a laminectomy

at the C3―C5 level. The dural sac was stretched, not

pulsed, and prolapsed into the wound. After opening of

the dura mater, about 3 mL of fluid discharge released

into the wound, which was collected for testing. The

spinal cord was pale and ischemic. After excision of

arachnoid adhesions, a pale-gray space-occupying lesion

located anterolaterally on the right was found; it grossly

compressed and displaced the spinal cord. After

identifying poles of the lesion, its capsule was opened.

The space-occupying lesion contained viscous yellowish

liquid. The space-occupying lesion and its capsule were

resected en bloc (Fig. 3).

An urgent biopsy revealed that the resected lesion

had an endodermal origin.

Surgery was performed in the presence of an

obstetrician-gynecologist, with continuous ultrasound

monitoring of the fetal condition (Fig. 4).

Fig. 1. SCT scans of the cervical spine. A large extramedullary space-occupying lesion is located anterolaterally at the C3―C5 level on the right and compresses the spinal cord.


The duration of surgery was 1.5 h. The total time of

anesthesia, including positioning of the patient, was

about 4 h. The amount of intraoperative blood loss was

less than 150 mL.

After surgery, the patient was transferred to the

Critical Care Department where she continued receiving

intensive therapy. No changes in the neurological status

occurred.

Postoperatively, the patient’s condition remained

unstable: she was conscious; episodes of fever, up to 39

°C, persisted, without any effect of administration of

antipyretics; artificial ventilation through the

tracheostomy was continued. There was marked

production of viscous sputum, requiring sanitation

bronchoscopy; the tendency to arterial hypotension

persisted, which required continuation of intravenous

infusion of norepinephrine; salt-wasting syndrome

typical of patients with a high level of spinal cord injury

developed [1].

A control MRI study of the cervical spinal cord

confirmed complete resection of the space-occupying

lesion (Fig. 5).

A histological examination of the lesion capsule

revealed the presence of cell-free masses with

hemorrhages as well as fibrous tissue with cylindrical

epithelium, the morphological structure of which was

typical of an endodermal cyst (Fig. 6).

A histological examination of the discharge collected

after opening of the dura mater revealed necrotized tissue

with hemorrhages (cerebral detritus).

On intensive therapy, the patient’s general condition

gradually stabilized: fever, hypoalbuminemia, and

anemia regressed. There was no improvement in the

neurologic status. According to an examination by an

obstetrician-gynecologist, the fetus continued to develop

normally; there were no indications for abortion.

Given expected prolonged subsequent treatment and

rehabilitation and upon agreement with relatives, the

patient was transferred to the Critical Care Department

of a regional hospital at the place of residence.

Further information on the fate of the patient and

the child was obtained from the doctors of appropriate

clinics by phone. The patient’s condition remained

relatively stable within a month after surgery; then, an

infectious process in the lungs worsened. This fact and

the need for antibacterial therapy with high doses of

potentially fetotoxic antibiotics, as well as significant

intrauterine fetal growth retardation, served as the basis

for the decision to terminate the pregnancy. Preterm

labor surgery (cesarean section) was performed at 29

weeks gestation, and a premature baby (boy) with a body

weight of 780 g, with an Apgar score of 6, was born. The

child was intubated and transferred to a specialized

perinatal center for artificial ventilation. According to

the available information, the child’s condition remained

severe by the time of manuscript preparation; the child

had several intracranial hemorrhages and was on artificial

ventilation. The mother’s condition after cesarean

section rapidly deteriorated. In the setting of bilateral

pneumonia, sepsis, and progressive multiple organ

failure, she died.

Discussion

Spinal pathology is the second most common disease

after traumatic brain injury among neurosurgical diseases

in Russia. Degenerative spine diseases are the most

common spinal pathologies. Primary tumors of the spinal

cord are relatively rare and account for only 10―15% of

all CNS tumors, or 1―2 cases per 100,000 people per

year [2]. Manifestations of spinal cord tumors during

pregnancy refer to casuistic cases. For example, A. Moles

et al. in their recent work on symptomatic vertebral

hemangiomas [3] (ones of the most common spinal

tumors) in pregnant females note that only 27 similar

cases have been reported in the literature since 1948.

Spinal cord tumors in pregnant females are even rarer.

Our patient had an extremely rare pathology ― an

endodermal cyst.

Fig. 2. T1- and T2-weighted MRI scans of the cervical spinal cord. a, b ― sagittal views; c ― an axial view; d ― 3D-MRI. (See the explanation in the text).


CASE REPORTS

An endodermal cyst is a cystic lesion resulting from

endogenous dysgenesis; it is often combined with other

developmental anomalies [4]. The endodermal cyst wall

consists of columnar epithelium with cylindrical,

cuboidal, or goblet cells that usually produce mucin.

Inside, the endodermal cyst is lined with the ciliated

epithelium. Depending on the location, there are

intraspinal (intradural extramedullary) cysts, which are

most common, and intracranial cysts that are usually

located in the posterior cranial fossa, anteriorly to the

brainstem. Intraspinal cysts often occur in the lower

cervical and upper thoracic spine. The cysts typically

have an intradural extramedullary (mainly anterior)

location [5]. Endodermal cysts usually have an isointense

Fig. 3. Intraoperative images. a ― after dissection of the dura mater; b ― after excision of arachnoid adhesions, a space-occupying lesion of a pale gray color is seen; c ― opening of the capsule

during resection of the lesion; d ― the space-occupying lesion and capsule resected en bloc; e, f ― the spinal cord after resection of the space-occupying lesion.


or hypointense signal on T1-weighted MR images and a

hyperintense signal on T2-weighted MR images and are

not contrast-enhanced. The lack of tracer uptake in the

cyst wall distinguishes endodermal cysts from other cystic

lesions, such as cystic schwannomas, cystic meningiomas,

cystic ependymomas, and cysticercosis [6]. Differential

diagnosis with arachnoid, epidermal, and dermoid cysts

should be performed. Despite the benign nature,

endodermal cysts can recur, therefore the main surgical

treatment option is total cyst resection [5, 6].

The symptoms of spinal cord space-occupying

lesions usually develop slowly and can be represented by

pain as well as motor and sensation disorders [7]. An

acute onset occurs extremely rare and usually is a

consequence of concomitant spinal stroke, as it obviously

occurred in the presented case. This is confirmed by the

rapid development of a neurological deficit and the

presence of hemorrhages in histological specimens. It is

important that the rate of deterioration and the severity

of clinical symptoms should be considered and profoundly

influence the management of these patients.

Examination and, if necessary, surgical intervention

should be performed as soon as possible, no later than the

“golden” day, and preferably earlier [8―10]. In the

presented case, surgery should be performed immediately,

even at the place of residence, to provide at least

decompression of the spinal cord. Transfer to the BNI

and stabilization of the patient’s general condition took

some time. The delay in surgery resulted in irreversible

changes in the tissues of the spinal cord, as evidenced by

the morphological picture of the fluid discharge released

after dissection of the dura mater, represented by a

necrotic tissue with hemorrhages.

In general, the management of pregnant females

with spinal pathology, especially in cases of severe

neurological symptoms, is extremely complex, and

information on this topic is quite limited [11―14].

Usually, one or two clinical cases with almost full-term

pregnancy or in the postpartum period are reported. In

this regard, the most interesting is a paper by I. Han et al.

[11], which summarizes the experience of managing 10

pregnant patients with different spinal pathologies at one

clinic for 13 years, and an article by K. Vijay et al. [14],

which describes 10 patients with vertebral hemangiomas.

Summarizing the data provided by the authors of these

two papers, we believe that two points are of crucial

importance: 1) neurological status of the pregnant female

and its dynamics and 2) gestational age of the fetus. In

the case of life-threatening neurological symptoms, full-

term or almost full-term pregnancy (32 weeks or more)

almost uniquely necessitates the following approach:

cesarean section and subsequent surgical treatment of the

mother. In the case of life-threatening neurological

Fig. 4. Intraoperative ultrasound examination of the fetus.

Fig. 5. Postoperative T1- and T2-weighted MR images of the cervical spinal cord in the sagittal (a) and axial (b) projections; there is no residual cyst; the area of vasogenic edema and ischemia at the cervical level is decreased in size.


CASE REPORTS

symptoms and early pregnancy, the authors of both works

suggest abortion because of the risk of fetal exposure to

X-rays and potentially fetotoxic drugs during diagnosis

and surgery in the first trimester of pregnancy.

We consider this recommendation as not quite

reasonable, especially given the recommendations of the

American Society of Radiologists, which contain the

only limitations related to the use of gadolinium as an

MRI tracer and a moderate risk of newborn

hypothyroidism associated with the use of iodine-

containing contrast agents [15].

Parturition in the case of incomplete pregnancy is an

approach that always requires serious argumentation.

A complication in premature newborns, such as

intracranial hemorrhage, is a well-known phenomenon

with the rate of occurrence, according to various

authors [16], ranging from 35 to 90%. The cause for this

high rate of the severe complication is now known: a

highly vascularized embryonic matrix is a substrate of the

developing brain. It is located in the subependymal space

of the lateral ventricles and undergoes a reverse

development at the 32―34th week of pregnancy.

Capillaries of this embryonic matrix are immature and

fragile and lack autoregulation mechanisms, which sets

the ground for hemorrhage in the case of even a slight

increase in cerebral blood flow [16]. In our opinion, the

only solution in our situation was an attempt to preserve

pregnancy by all means. Obviously, our colleagues had

solid indications for operative delivery in the case of

incomplete pregnancy. However, the consequences of

prematurity in the form of typical complications affected

the further fate of the baby.

Conclusion

The presented clinical case is a rare coincidence of

unfavorable circumstances: the presence of an

extramedullary space-occupying lesion in the patient,

lesion-induced spinal stroke, and incomplete pregnancy.

All these factors influenced the unsatisfactory outcome

of the disease. An endodermal cyst is a rare cystic lesion

of the intradural space, which we encountered for the

first time in our practice. Spinal stroke caused by an

anterior endodermal cyst at the cervical spinal cord level

in a pregnant female had not been reported in the

literature before, so we tried to present in detail this case

and the features of microsurgery, anesthesia, and critical

care. Regarding the management of the patient, we

believe that the decision of surgery should have been

made within the first 12 h after the disease onset. The

outcome of later interventions is unfavorable in most

cases, and the neurological deficit is irreversible.

Treatment of patients with combined pathology requires

participation of various specialists. In our case, the fetus

condition was controlled by obstetrician-gynecologists.

Unfortunately, prolongation of pregnancy up to 37―38

weeks was excluded in the presented situation. Was it

possible to avoid this treatment outcome? In our view,

under these circumstances, unfortunately not.


Fig. 6 (a, b). A morphological picture of the endodermal cyst wall consisting of the columnar epithelium with cylindrical, cuboidal, or goblet cells. Inside, the endodermal cyst is lined with the ciliated epithelium.


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Commentary

The article describes a rare clinical case of intensive therapy

and surgical treatment of a 24-year-old patient who was

admitted to the Neurosurgical Institute at 20 weeks gestation

with spinal stroke associated with a space-occupying lesion of

the cervical spinal cord ― an endodermal cyst.

Undoubtedly, the presented clinical case is of great

practical importance and real interest. Pregnancy combined

with spinal pathology is rarely encountered by the neurosurgeon

and neurointensivist in their practical work and is always

associated with considerable difficulties in choosing the

treatment strategy and tactics. In the present case, the authors

encountered a combination of unusual and, unfortunately,

extremely unfavorable factors that occurred simultaneously in

the patient. These factors included a very rapid development of

the clinical and radiographic picture of the tumor in the form of

spinal stroke, a rare histological type of the space-occupying

lesion, and delayed radical surgery (because the patient had no

surgery at a hospital where she was initially admitted).

Of great interest is the surgical approach used by the

operating team, including the surgical stage with the patient in

a lateral position due to pregnancy, which is a non-standard

solution for modern interventions in the cervical spine,

especially with intraoperative ultrasound monitoring of the

fetus condition. Also, of interest is the successful treatment at

the Neurocritical Care Department, which included reversal of

life-threatening conditions, such as salt-losing syndrome and

hyperthermia.

The perioperative period was complicated by not quite

ordinary phenomena, the genesis of which as well as initial

severity of the patient’s condition are not clear because of

limited world experience. Preserving pregnancy in this situation

is also debatable.

Undoubtedly, only joint efforts of doctors of different

specialties in a well-equipped hospital are able to solve the

problems of treatment of spinal cord space-occupying lesions

in the pregnant patient with severe and rapidly worsening

neurological symptoms. Unfortunately, surgical care, at least

decompression of the spinal canal, was not provided in the first

hours after admission of the patient to a local hospital. Despite

the fatal outcome of the disease for the mother and dubious

prospects for the newborn, this clinical case demonstrates high

skills of the authors and the coherence of their work.

A.O. Gushcha, A.A. Kashcheev (Moscow, Russia)


CASE REPORTS

doi: 10.17116/engneiro201680674-78

Extrapontine Myelinolysis Developed After Aneurysmal Subarachnoid Hemorrhage (a Case Report and Literature Review)S.A. GOROSHCHENKO, A.YU. IVANOV, L.V. ROZHCHENKO, N.E. IVANOVA, YU.M. ZABRODSKAYA, O.YU. RAZMOLOGOVA, A.N. KONDRAT’EV, E.G. POTEMKINA, A.YU. DMITRIEVSKAYA, G.P. BLAGORAZUMOVA, S.D. RADZHABOV, A.E. PETROV, A.A. IVANOV, P.S. SINITSYN, V.V. BOBINOV

Polenov Russian Scientific Research Institute of Neurosurgery, the Branch of the Almazov Federal North-West Medical Research Centre, St. Petersburg, Russia

Topicality. Central pontine and extrapontine myelinolysis is a rare and dangerous form of the demyelinating process of unknown origin, the development of which is associated with abrupt changes in the serum sodium level (hypernatremia).Objective — to describe a rare case of extrapontine myelinolysis complicating the hemorrhagic period of anterior communicating artery aneurysm rupture as well as to demonstrate the ability to intravitally diagnose this condition.Conclusions. Clinical vigilance of extrapontine myelinolysis may promote the timely diagnosis and treatment of this disease that is a potential cause of death. Pulse-therapy with glucocorticoids alleviates neurological symptoms and stabilizes the patient’s condition.

Keywords: hypernatremia, subarachnoid hemorrhage, extrapontine myelinolysis, glucocorticoids.


The paper is published to describe the development,

diagnostic capabilities, and treatment of a rare life-

threatening complication of subarachnoid hemorrhage.

Clinical case

A 58-year-old female patient was transferred to the

Department of Cerebral Vascular Surgery of the Polenov

Russian Scientific Research Institute of Neurosurgery

(PRSRIN) from a city hospital on the 15th day after

subarachnoid hemorrhage (SAH) from an anterior

communicating artery (AComA) aneurysm. The patient

was admitted with a WFNS grade 1 SAH. Neurological

status: the patient had clear consciousness and cerebral

symptoms with signs of intracranial hypertension and

focal lesions of the frontal lobes. Spiral computed

tomography (SCT) of the head revealed narrowing of the

subarachnoid spaces in the right cerebral hemisphere.

There was no hydrocepalus and deformity of the ventricles.

The patient had a concomitant disease, rheumatoid

polyarthritis, and constantly received 20 mg of

methotrexate per week. Spiral computed tomographic

angiography of the brain revealed a saccular aneurysm

and diverticula of the AComA (Fig. 1).

The patient underwent urgent osteoplastic craniotomy

and microsurgical clipping of the AComA aneurysm. In

the postoperative period, there was no worsening of

cerebral and focal symptoms. The patient received

antibacterial, anti-edematous, and cerebroprotective

therapy (medocef, nimotop, cytoflavin, mexidol). In a

blood chemistry panel, the sodium level changed between

144―152 mmol/L; there were no other changes. On the

14th postoperative day, the patient’s condition sharply

deteriorated: the consciousness level worsened to

profound obtundation with development of spastic

tetraparesis of up to 1 point. A CT examination revealed

signs of right hemisphere edema with a brain displacement

of 7 mm to the left. Magnetic resonance imaging (MRI)

of the brain detected multiple areas of a hyperintense T2-

weighted image (T2-WI) signal, having clear contours in

the area of the corpora quadrigemina, both cerebral

peduncles, and oral pons (Fig. 2). A blood chemistry

panel revealed hypernatremia of up to 170 mmol/L as

well as elevated AST (58.5 U/L) and ALT (103 U/L)

levels.

The patient’s condition was assessed as the

development of pontine and extrapontine myelinolysis.

Pulse-therapy with glucocorticoids (solu-medrol for 3

days according to the schedule) provided a pronounced

positive effect: recovery of the consciousness, partial

restoration of limb movements (up to 4 points), and

normalization of natremia. However, a week later (on day

28 of the postoperative period), negative changes again

occurred in the patient’s condition: bulbar symptoms,

tetraplegia, and locked-in syndrome. An EEG

examination revealed gross diffuse changes clearly

predominating in the diencephalic brainstem structures.

A blood test again detected hypernatremia (172 mmol/L).

A cerebrospinal fluid test demonstrated a significant

increase in the myelin basic protein level (460 ng/mL,

with the normal level being less than 1 ng/mL) as well as a

sharp increase in the anti-myelin-associated glycoprotein

level (4,850 U/mL, with the normal level being

1000 U/mL); the S100 protein and neuron-specific

enolase levels were not significantly increased. Repeated

pulse-therapy with glucocorticoids had no significant

effect. The patient’s condition progressively worsened,

multiple organ failure (bilateral pneumonia and renal,

hepatic, and cardiovascular failure) deteriorated, which

led to death of the patient.

Autopsy findings: the white matter of the brain was of

a pale color, soft elastic in its texture, with bulging over


the cut surface in the subcortical nuclei area and in the

pons; the grey matter of the subcortical nuclei and thalami

was of a heterogeneous color, with small yellowish foci

(Fig. 3).

A histological examination of fragments of the

subcortical nuclei, thalami, and white matter of the

hemispheres as well as a cross-section of the pons, staining

with hematoxylin and eosin, and Nissl (for detection of

the Nissl substance in neurons) and Spielmeyer (for

myelin) staining were performed. In all the examined

fragments, diffuse foci of complete demyelination were

detected; edema in the form of a spongy transformation of

the white matter was present in the perifocal area of the

foci (Fig. 4).

In the demyelination foci, there was destruction of

the brain tissue, disintegration of neuropils, neuronal

shrinkage, the presence of eosinophilic bodies, moderate

gliosis with the microglial response, and swollen

oligodendrocytes (Fig. 5).

Neurons in these foci had dystrophic changes:

pericellular edema, moderate neuronophagia, foci of

neuronal dropout, and granular disintegration of the Nissl

substance (Fig. 6).

Therefore, the patient had diffuse microfocal

demyelination in the white matter of the hemispheres and

brainstem.

Discussion

Central pontine myelinolysis (CPM) was first

described by R. Adams et al. [1] (1959) in a patient with

chronic alcoholism, which was defined as osmotic

demyelination syndrome. Later, CPM was detected in

patients with diabetes mellitus, systemic lupus

erythematosus, renal failure, pituitary adenoma, and

cerebellar astrocytoma [2, 3]. The development of CPM

after liver transplantation was reported. As it was

demonstrated in an experimental model of CPM in rats,

rapid administration of hypertonic saline (rapid

hypernatremia) resulted in extracellular edema of the

brain, provoking swelling of oligodendrocytes and

destruction of the myelin sheath [4]. Damage to the

myelin sheath can develop not only in the pons but also in

other brain structures, both in combination with CPM

and alone [5]. These disorders were called extrapontine

myelinolysis (EPM); in this case, demyelination foci can

occur in the brain peduncles, thalamus, corpus callosum,

geniculate bodies, and other brain structures [5]. Pontine

and extrapontine myelinolysis may be caused by other

hyperosmolar states [6].

The pathogenesis of this rare demyelinating process

has not been sufficiently studied. Currently, its

development is believed to be associated with a sharp

disturbance of the electrolyte (sodium) balance and blood

osmolarity [3, 6].

The major regulator of electrolyte metabolism in the

body is the hypothalamus. Studies of researchers guided

by Prof. M.V. Ugryumov (neurohistological,

neurohistochemical, and ultrastructural studies) at the

PRSRIN proved involvement of the hypothalamus in the

genesis of the degenerative-dystrophic process in the

nervous system and internal organs [7, 8]. The

development of the pathological process may involve

decreased functional activity of the hypothalamic

neurosecretory centers, which leads to deficiency of

viscerotropic peptide neurohormones in the general

circulation. The hormones maintain homeostasis, change

permeability of biological membranes, and affect various

aspects of metabolism, which, in turn, may cause gross

disturbances of electrolyte metabolism (hypo- and

hypernatremia).

The clinical picture of myelinolysis includes spastic

tetraparesis, pseudobulbar palsy and mental disorders [9],

Fig. 1. SCT angiography of the brain. a, b ― a ruptured saccular aneurysm of the AComA (indicated by arrows).


CASE REPORTS

epileptic seizures [10], Parkinson’s syndrome, and

locked-in syndrome [12―14].

CPM and EPM are primarily diagnosed based on

neuroimaging data. Myelinolysis appears as a high H2O

content area on the X-ray film and can resemble infarction

on the SCT scan. The method of differential diagnosis of

myelinolysis is MRI. Brain lesion areas are characterized

by a homogeneous high signal on T2-WI MR images and

by a low signal, the absence of perifocal edema, and mass-

effect signs on T1-WI MR images. A characteristic feature

of this pathology is non-involvement of the pontine

tegmentum and anterolateral pontine structures. The

affected area can involve the midbrain, periventricular

white matter, internal and external capsules, and corpora

callosa. MRI findings of bilateral symmetric lesions of the

thalami and basal nuclei in combination with brainstem

lesions facilitate the correct clinical interpretation of

myelinolysis [15].

A significant contribution to the differential diagnosis

in the present case was made by the data of chemistry

blood and cerebrospinal fluid panels that revealed elevated

levels of the demyelination markers ― the myelin basic

protein (its level was increased hundreds-fold) and

antimyelin-associated glycoprotein, with no increase in

the S100 protein (a marker of damage and inflammation

of the brain) and neuron-specific enolase (a marker of

ischemia) levels. This indicates the demyelinating process

in the brain, developing without signs of ischemia and

inflammation.

In the literature, there are separate reports on the use

of high doses of corticosteroid hormones [16] and

plasmapheresis for the treatment of EPM [17―19]. The

Fig. 2 (a―d). T2-WI and FLAIR MRI of the brain. Arrows indicate changes in the brainstem and subcortical nuclei.


use of pulse-therapy with glucocorticoids enabled us to

slow down the process in the presented case as well as to

achieve pronounced regression of the neurological

symptoms. However, the intravital diagnosis of this rare

complication did not help stop the development of severe

neurodystrophic lesions of internal organs, which led to

multiple organ failure that caused patient’s death.


Fig. 6. A microspecimen of the white matter from the subcortical nuclei area. 1 ― a dead neuron; 2 ― granular disintegration of the Nissl substance, initial

neuronal karyolysis; 3 ― a deformed neuron with chromatolysis. Nissl staining,

×400.

Fig. 3. A gross specimen. A cross section of the pons: 1 ― developing microcysts; 2 ― bulging of the white

matter.

Fig. 4. A microspecimen of the white matter from the subcortical nuclei area. 1 ― demyelination area; 2 ― edema in the perifocal area with spongy

transformation; 3 ― area of positive staining of myelin fibers. Spielmeyer

staining, ×200.

Fig. 5. A microspecimen of the white matter from the subcortical nuclei area. 1 ― neuronal death; 2 ― neuronal shrinkage; 3 ― eosinophilic bodies. Staining

with hematoxylin and eosin, ×400.

REFERENCES1. Adams RD, Victor M, Mancall EL. Central pontine myelinolysis: a hither

to undescribed disease occurring in alcoholic and malnourished patients.

AMA Arch Neurol Psychiatry. 1959 Feb;81(2):154-172.

doi: 1959.02340140020004

2. Atkin JJ, Coady AM, White MC, Mathew B. Hyponatraemia secondary to

cerebral salt wasting syndrome following routine pituitary surgery. Eur J Endocrinol. 1996;135:245-247.

doi 10.1530/eje.0.1350245

3. Stakhovskaya LV, Erokhina LG, Leskova NN, Gubskiy LV. Central pontine

and extrapontine myelinolysis. Zhurnal nevrologii i psikhiatrii. 2000; 100: 2:

55-58. (In Russ.).

4. Norenberg MD, Papendick RE. Chronicity of hyponatremia as a factoir in

experimental myelinolysis. Ann Neurol. 1984;15:544-547.

doi 10.1002/ana.410150606

5. Hadfield MG, Kubal WS. Extrapontine myelinolysis of the basal ganglia with-

out central pontine myelinolysis. Clin Neuropathol. 1996 Mar-Apr;15(2):96-100.

doi 10.1007/3-540-27660-2_89

6. Bourgouin PM, Chalk С, Richardson J, Duang H, Vezina JL. Subcortical

white matter lesions in osmotic demyelination syndrome. Am J Neuroradiol. 1995;16:1495-1497.


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7. Polenov AL. The problem of central neurodystrophies of internal organs. Leningrad: Meditsina. 1972. (In Russ.).

8. Tayushev KG. Hypothalamogenic degenerative-dystrophic process. Saint

Petersburg: Eskulap. 2002; 202. (In Russ.).

9. Laureno R, Karp BI. Myelinolysis after correction of hyponatremia. Ann Intern Med. 1997;126:1:57-62.

doi 10.7326/0003-4819-126-1-199701010-00008

10. Girmenia F, Colasimo Di Biasi C, Faroni J, Pozzilli C. Central pontine my-

elinolysis: report of an asymptomatic case. Ann Ital Med Int. 1995;10(1):53-54.

11. Greenberg WM, Shah PJ. CPM in polydipsic psychiatric patients. Am J Psychiat. 1993;150:842-843.

doi 10.1176/ajp.150.5.842-b

12. Go M, Amino A, Shindo K, Tsunoda S, Shiozawa Z. A case of central pon-

tine myelinolysis and extrapontine myelinolysis during rapid correction of

hypernatremia. Kinsho Shinkeigaku. 1994;34:11:1130-1135.

13. Morlan L, Rodriguex E, Gonzalez J, Jimene-Ortiz C, Escartin P, Liano H.

Central pontine myelinolysis following correction of hyponatremia: MRI

diagnosis. Eur Neurol. 1990;30:1:149-152.

doi 10.1159/000117333

14. Ardizzone G, Arrigo A, Schellino MM, Stratta C, Valzan S, Skurzak S,

Andruetto P, Panio A, Ballaris MA, Lavezzo B, Salizzoni M, Cerutti E.

Neurological complications of liver cirrhosis and orthotopic liver trans-

plant. Transplant Proc. 2006;38(3):789-792.

doi: 10.1016/j.transproceed.2006.01.039

15. Ho VB, Fitz CR, Yoder CC, Geyer CA. Resolving MR features in osmotic

myelinolysis (central pontine and extrapontine myelinolysis). Am J Neuro-radiol. 1993;14(1):163-167.

16. Kallakatta RN, Radhakrishnan A, Fayaz RK, Unnikrishnan JP, Kesa-

vadas C, Sarma SP. Clinical and functional outcome and factors predicting

prognosis in osmotic demyelination syndrome (central pontine and/or ex-

trapontine myelinolysis) in 25 patients. J Neurol Neurosurg Psychiatry.

2011;82(3):326-331.

doi: 10.1136/jnnp.2009.201764

17. Ludwig KP, Thiesset HF, Gayowski TJ, Schwartz JJ. Plasmapheresis and

Intravenous Immune Globulin Improve Neurologic Outcome of Central

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doi: 10.1345/aph.1P371

18. Saner FH, Koeppen S, Meyer M, Kohnle M, Hergel-Rosenthal S, Soti-

ropoulos GC, Paul A, Radtke A, Malago M, Broelsch CE. Treatment of

central pontine myelinolysis with plasmapheresis and immunoglobulins in

liver transplant patient. Transpl Int. 2008;21(4):390-391.

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19. Dzyadz’ko AM, Katin ML, Rummo OO, Shcherba AE, Santotskiy EO,

Minov AF, Gurova MYu, Chugunova OA, Slobodin YuV, Zubritskiy SМ,

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(1): 89-95. (In Russ.).

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Commentary

The article presents a case of surgical treatment of a patient

during the subacute stage of subarachnoid hemorrhage from an

anterior cerebral (communicating) artery aneurysm, which was

complicated by the development of pontine and extrapantine

myelinolysis in the late postoperative period, discusses this rare

complication, and reviews the literature. The article describes

the clinical course of the disease, data of CT and MRT

examinations in the postoperative period, results of chemistry

blood and cerebrospinal fluid panels (including tests for markers

of demyelination, inflammation, and ischemia), as well as

results of pathomorphological and histological examinations of

the brain after the patient’s death. On the basis of these data,

the authors conclude that the patient had the demyelinating

process in the brainstem and basal ganglia caused by osmotic

disorders.

Acute pontine and extrapontine myelinolysis is a rare

condition; however, the international and domestic literature

reports a sufficient number of clinical cases of this condition as

well as studies of its pathogenesis. In most studies, this condition

is considered to result from hyponatremia or rapid and abrupt

electrolyte changes during correction of hyponatremia that, in

turn, is often caused by various somatic pathologies.

In the presented case, it is difficult to reliably conclude on

the causes of demyelination because the data on electrolyte

disturbances and infusion therapy are fragmentary. There is

also no information about the presence and severity of

angiospasm in the preoperative and, particularly, postoperative

periods, which may also be a cause of diencephalic disorders,

especially given postoperative edema of the right hemisphere

and postoperative hypernatremia. It is not entirely clear what

led to the patient’s death because it is not indicated on what day

after surgery she died, and the cause of death is not cerebral

disorders but multiple organ failure typical of patients being in

a serious condition for a long time. There is no discussion of a

relationship between the revealed changes and the patient’s

autoimmune disease as well as long-term therapy with

immunosuppressors. There are questions about quality of the

morphological study and its description that does not provide

an unambiguous confirmation of demyelination and may also

indicate ischemia.

However, the article is of undoubted interest, drawing

attention to the problem of pathogenesis of various

complications in neurosurgical patients and their differential

diagnosis. In this regard, of great interest are chemistry blood

and cerebrospinal fluid panels for demyelination markers,

which are rarely used in neurosurgical practice.

O.B. Belousova, I.A. Savin, O.A. Gadzhieva, L.V. Shishkina (Moscow, Russia)


doi: 10.17116/engneiro201680679-83

Extradural Spinal Cord Hemangioblastoma (a Case Report and Literature Review)N.A. KONOVALOV, L.V. SHISHKINA, D.S. ASYUTIN, R.A. ONOPRIENKO, V.A. KOROLISHIN, B.A. ZAKIROV, M.A. MARTYNOVA, I.U. CHERKIEV, A.L. POGOSYAN, S.YU. TIMONIN


Hemangioblastoma is a rare CNS vascular tumor that develops sporadically and can also be associated with von Hippel—Lindau disease. Hemangioblastomas account for 2—6% of all spinal cord tumors and rank third in the structure of intramedullary space-occupying lesions of the spinal cord. For the first time in our practice, we observed a dumbbell paravertebral hemangioblastoma. The international literature reports only 3 cases of the tumor with this growth type.

Keywords: hemangioblastoma, von Hippel—Lindau disease, extradural dumbbell tumor.

e-mail: [email protected] © Group of authors 2016

Case report

Patient N., 56 years old, was admitted to the

Burdenko Neurosurgical Institute on 03.09.14 with

complaints of pain in the lumbosacral region irradiating

to the left leg, as well as sensory disorders in the form of

hypesthesia along the posterior surface of the left femur

and tibia. The history showed that the patient suffered

from back pain for a long time, pain gradually increased

over time and became permanent. The patient repeatedly

received drug therapy aimed at treatment of degenerative

disc disease, which did not result in improvement. Since

2006, the pain intensified and occurred in the rest, sitting,

and lying positions. In August 2013, the pain became

very intense and conservative therapy still was ineffective.

In this regard, MRI of the lumbosacral spine was carried

out, which revealed extradural mass lesion having

paravertebral spread at L4 —L5 into the intervertebral

foramen on the left. The mass was oval-shaped, sized

16x25x10 mm. Spinal angiography with contrasting of

tumor’s own vascular network at the level of L4 vertebra

was carried out (images are not shown). The patient was

admitted to neurosurgical department at the place of

residence for surgical treatment. The attempt of tumor

resection was unsuccessful. Histological examination of

resected fragment led to conclusion that it was

ganglioneuroma.

Control MRI 12 months after surgery showed the

same MR pattern as preoperative one (Fig. 1).

Resection of extradural paravertebral dumbbell

tumor on the left at L4—L5 was carried out at the

Burdenko Neurosurgical Institute on 11.09.14.

Operation

Patient’s position on the operating table: prone

position under a combination anesthesia with

endotracheal ventilation. Tumor level was localized

using O-arm intraoperative CT tomograph, images were

taken in the lateral and frontal planes in 2D-mode.

Paramedian skin incision was performed a few

centimeters to the left from the scar resulting from the

previous surgery. Caspar surgical microscope and

retractor system were used to approach the tumors. The

use of this expander minimized trauma to surrounding

tissues. Hemilaminectomy on the left at the level of L4

vertebral arch was carried out using microsurgical

instruments and Zimmer high-speed bur. Orange

elongated tumor sized 3x2 cm was observed. The tumor

was located in the L4—L5 intervertebral foramen and

was shaped similar to neurinoma. Extradural portion of

the L4 root on the left was determined to be the growth

origin. Major arterial vessel supplying the tumor was

detected during tumor separation along its perimeter. It

was coagulated and transected. Proximal part of the

tumor and root were ligated and then the tumor and

nerve root were coagulated and removed en bloc.

Hemostatic material was placed to the bed of resected

tumor (Fig. 2). The wound was closed using the standard

scheme.

In the postoperative period, pain regression was

observed. The patient was aroused on day 1 after the

operation. After 7 days, the patient was discharged home

in satisfactory condition. Histological diagnosis:

hemangioblastoma. Follow-up MRI study was carried

out 3 months after the operation (Fig. 3).

The histological characteristics of the tumor

Histological examination (Fig. 4) confirmed the

microscopic diagnosis of hemangioblastoma. Tumor

consisted of two types of cells: stromal cells with optically

empty cytoplasm and a large number of vascular cells.

The tumor was surrounded by a thin layer of fibrous

tissue closely bordered by nervous tissue fragments and

clusters of ganglion cells (Fig. 5).

During the study, adjacent nerve stem was discovered

(Fig. 6); the same finding was reported by R. Pluta et

al. [2].

Comparative analysis of the results of surgical treatment of hemangioblastomas

Spinal hemangioblastomas belong to the group of

highly vascularized tumors, which are often characterized

by intramedullary localization. Hemangioblastoma


CASE REPORTS

account for 2—6% of all spinal cord neoplasms and rank

third in the structure of intramedullary space-occupying

lesions of the spinal cord [1]. In our case, the tumor was

paravertebral, dumbbell-shaped, and was not connected

to the dura mater. In the international literature [2—4],

we found three case reports describing patients with

similar localization of a space-occupying mass. The

Table shows some information about these patients, in

particular, clinical status and results of surgical treatment

(cases 1—3) and compares these data to the case descried

in our study (case 4).

When evaluating data shown in the Table, it is clear

that there were certain differences in the clinical

presentation of the disease. Thus, case 3 was characterized

by acute onset of the disease, where strong pain evolved

within 2 weeks, followed by admission of the patient to

neurosurgical hospital. In two other cases, (cases 1

and 2), as well as in our patient (case 4), there was a 2—20

years-long history. The tumor mainly manifested in the

form of radiculopathy characterized by pain in the

lumbosacral spine radiating to the leg, and also radicular

sensory disorders. Dysfunction of pelvic organs (urinary

incontinence) was observed in the case 3, possibly due to

compression of the roots of “cauda equina”.

The Table shows that preoperative clinical and X-ray

examination suggested correct histological diagnosis

Fig. 1. Hemangioblastoma of L4 root. The series of T2-weighed MRI scans in the sagittal, frontal and axial projections (a, b, c) shows extradural hypointense space-occupying mass at L4—L5 vertebrae

characterized by hyperintense foci and dumbbell-shaped paravertebral growth to the left (the tumor is shown by white arrows). The sagittal and frontal views (a, b) show

pronounced vasculature (indicated by red arrows), which corresponds to multiple areas of hypointense signal in T2-weighed mode.

Fig. 2. Operation stages. a, b — exposure and mobilization of the solid part of the tumor; c — ligation of the neck of the tumor of the L4 root; d — tumor resection along with the root. 1 — solid

portion, 2 — L4 root, 3 — gaine radiculaire, 4 — tumor bed.


only in one case (case 1) owing to the fact that this patient

with von Hippel—Lindau disease was diagnosed with

multiple CNS hemangioblastoma. In 2 cases (cases 2

and 3) preoperative MRI study led to a presumable

diagnosis of radicular neurogenic tumor, neuroma

(schwannoma). In our case (case 4), the tumor was

considered as paravertebral ganglioneuroma of the L4

root, corresponding histological diagnosis was made after

the first operation at the place of residence.

Our analysis of X-ray data led to the following

conclusions. Firstly, the studies should be contrast-

enhanced. Second, detection of pathologically dilated

tortuous vessels within the spinal canal around the

neoplasm is a pathognomonic sign of hemangioblastoma.

The vessels are best visualized in T2-weighted mode.

Thirdly, the solid component of the tumor has hypo-

intensive or iso-intensive T1-weighed MR signal, and

cystic cavities have T1- and T2-weighed signal similar to

that of the CSF or brighter T2-weighed signal. At least

one of the above MRI features suggests a vascular tumor,

and in this connection selective angiography can be

recommended [4, 5].

When evaluating the outcomes of surgical treatment,

we should note that tumors were completely resected in

all four cases (see Table). This was accompanied by

regression of pain syndrome. Possible occurrence of

minor neurological deficit should be considered as an

inevitable consequence of the operation rather than a

complication, since the tumor is most often removed

together with the root, where it originates from.

Fig. 6. Hemangioblastoma and adjacent nerve stem (arrow). H & E stain, magnification x 50.

Fig. 3. T2-weighed MRI, sagittal and axial views (a, b, c, d) after resection of hemangioblastoma.

Fig. 4. Hemangioblastoma. Stromal cells with optically empty cytoplasm (shown by red arrow) and vascular cells (shown by blue arrow).H & E stain, magnification x200.

Fig. 5. Hemangioblastoma (shown by red arrow) and clusters of ganglion cells (shown by green arrow). H & E stain, magnification x100.


CASE REPORTS

!!! Обзор публикаций о хирургическом лечении корешковых гемангиобластом спинного мозга

Author and

year of

publication

Case

NoSex

Age

(years)

Anamnesis

morbi,

months

Location

HL (Von

Hippel–

Lindau)

Presumable

preoperative

diagnosis

AG with

emboli–

zation

Clinical

presentation

History,

months

Treatment

outcome

Ryszard M.

Pluta, 2003

1 F 38 120 EL S1-S2

left

+ Hemangi o-

blastoma

+ RPS at S1—

S2, SD

12 Regression

RPS

Masaaki

chazo NO,

1999

2 F 48 24 EL-DS

L5 left

— Neurog enous

tumor (Neuro-

fibroma,

schwannoma)

− MD, SD 12 Regression

MD

María

Román-de

Aragón,

2014

3 M 48 1 EL-DS

L4 right

— Neuri-

noma

+ PS, RPS,

SD, DPO

36 Regression PS,

RPS, SD,

DPO

N.A.

Konovalov,

2016

4 F 56 240 EL-DS

L4 left

— Para-

ganglioma

— PS, RPS 3 Regression PS,

RPS

Footnotes. EL — extradural location, DS — dumbbell-shaped tumor, PS — pain syndrome, RPS — radicular pain syndrome, SD — sensory disorders, MD — motor

disorders, DPO — dysfunction of pelvic organs.

Discussion

Extramedullary hemangioblastomas are a fairly rare

pathology and there are no standards for their resection.

Since the aforementioned case was the first case of

extradural hemangioblastoma in our practice, we applied

microsurgical resection technique similar to that used for

resection of dumbbell tumors. Unfortunately, we did not

embolized the vessel supplying the tumor, which resulted

in bleeding from that vessel, the radicular artery, during

separation of the paravertebral portion of the tumor,

going beyond the intervertebral foramen. The bleeding

was successfully stopped using bipolar coagulation.

As the second stage, we exposed tumor poles, while

maintaining the dilated tumor draining veins, since we

believe that it is a string requirement. Hemangioblastomas

are well encapsulated and can be easily separated from

the surrounding tissue. Manipulations inside the tumor

capsule are dangerous since pronounced bleeding is

possible, which is usually difficult to control and can

completely obscure the entire field of view. Next, we

exposed the part of the tumor adjacent to the dura; the

root entering the tumor was ligated to prevent liquorrhea

from the gaine radiculaire. In our case, hemangioblastoma

could not be separated from the root because they were

adhered to each other. Therefore, hemangioblastoma has

been removed together with the L4 root. Despite the

transection of the root, no negative symptoms in the

form of increasing muscle weakness were observed in

patient’s left foot in the postoperative period. Tumor

resection resulted in formation of a deep bed. We carefully

examined the bed and suppressed hemorrhage from small

blood vessels. In this situation, hemostasis should be

carried out with hemostatic material without the use of

bipolar coagulation.

Conclusions

Extradural hemangioblastoma is a very rare disease.

However, in the cases, where MRI signs of a vascular

tumor are detected, further examination in required,

which may include CT perfusion study, as well as selective

angiography, when necessary. In the case of

hemangioblastoma with clearly differentiated supplying

vessels, embolization is advisable to reduce the risk of

intraoperative hemorrhage.

In our view, resection technique for extradural

hemangioblastomas is similar to operations carried out

for other tumors characterized by mostly paravertebral

dumbbell growth.



REFERENCES1. Mehta GU, Asthagiri AR, Bakhtian KD, Auh S, Oldfield EH, Lonser RR.

Functional outcome after resection of spinal cord hemangioblastomas as-

sociated with von Hippel—Lindau disease: Clinical article. Journal of Neu-rosurgery Spine. 2010;12(3):233-242.

2. Pluta RM, Wait SD, Butman JA, Leppig KA, Vortmeyer AO, Oldfield EH,

Lonser RR. Sacral hemangioblastoma in a patient with von Hippel—Lindau

disease: case report and review of the literature. Neurosurgical focus.

2003;15(2):1-4.

3. Chazono M, Shiba R, Funasaki H, Soshi S, Hattori A, Fujii K. Hemangio-

blastoma of the L-5 nerve root: Case illustration. Journal of Neurosurgery Spine. 1999;90(1):160-160.

4. Román-de Aragón M, Márquez T, Isla A, Gómez-de la Riva Á. Hemangio-

blastoma radicular extraforaminal de la raíz L4 derecha. Neurocirugía.

2014;25(6):286-289.

5. Kornienko VN, Pronin IN. Diagnosticheskaya neiroradiologiya. T 5;307-

314.

Hemangioblastoma is a highly vascularized benign tumor,

consisting of clustered thin-walled vessels of various calibers,

whose interstitial cells contain lipid-rich cytoplasm. In most

cases, spinal hemangioblastomas are intramedullary and

account for 2 to 8% of all intramedullary neoplasms, being

exceeded in incidence only by ependymomas and astrocytomas.

Spinal hemangioblastoma account for up to 20% of all CNS

hemangioblastomas. In rare cases, these tumors can be

extramedullary, and, in exceptional cases, even extradural.

Despite the preferential location of the tumor within the central

nervous system, no histological relationship between this tumor

and glial tissue was found. This explains the fact that the disease

occurs not only in the boundary zone between the central and

peripheral part of the nervous system (intradural extramedullary

hemangioblastomas are usually connected with the dorsal

surface of the spinal cord or intradural portion of the posterior

root), but also in the distant areas. The literature describes

hemangioblastomas of radial and sciatic nerves.

Cases of extramedullary tumors are extremely rare, which

complicates the choice of correct diagnosis and surgical

treatment of this pathology.

In the present article, the authors describe the clinical

presentation, diagnostic algorithm, and preoperative

preparation of patients with extradural hemangioblastomas,

taking into account available literature. Special attention is paid

to the surgical techniques of tumor node resection.

The article is of great interest to a wide range of

neurosurgeons.

G.Yu. Evzikov (Moscow, Russia)

Commentary


CASE REPORTS

doi: 10.17116/engneiro201680684-89

Infant Form of Alexander Disease (Clinical Case and Literature Review)R.A. VASIN, M.A. KRASNIKOV, S.V. VASINA

Regional Children’s Hospital, Lipetsk, Russia

We present a case of the infant form of Alexander disease. The case is unique because the patient’s examination was started at the preclinical stage and continued during the manifestation and fastigium of the disease. We present rare images obtained during neurosonography at the preclinical stage of the disease as well as the unique findings of MRI studies. The MRI findings at disease onset and 3 years later indicate that the infant form of Alexander disease is characterized by clinical stages.

Keywords: Alexander disease, leukodystrophy, hydrocephalus.


Alexander’s disease is a rare hereditary disease,

characterized by progressive degeneration of white

matter of the brain. The disease is caused by mutation in

a gene, which encodes GFAP (glial fibrillar acidic

protein) protein. Russo et al. (1976) distinguish three

forms of the disease based on the time of its manifestation:

infant form, which manifests at the age from 0 to 2 years,

adolescent form, from 2 to 12 years, and adult form, after

12 years of age [1]. Some authors [2—4] also describe

neonatal form. The infant form accounts for 63 to 80% of

all cases [3, 5, 6].

Recently, another classification scheme has been

gaining traction which is based on the localization of the

lesion and clinical presentation. Prust et al. (2011)

identify types I and II of the disease. Type I includes early

forms with predominantly frontal leukodystrophy, while

type II includes mainly cerebellar lesions and lesions of

stem structures. The median survival for type I is 14

years, for type II, 25 years [1]. It is believed that the

earlier the disease manifests, the more malignant is its

course. This is especially true of the neonatal form [2, 3].

At the same time, some experts note unpredictable course

of the disease at any age and do not consider age-based

classification to be relevant [2].

S. Marjo van der Knaap et al. [7] offer five MRI

criteria for establishing the diagnosis of Alexander's

disease:

- extensive changes in the white matter of the cerebral

hemispheres, mainly in the frontal lobes;

- periventricular rim with high intensity T1 signal

and low level of T2 signal;

- changes in basal ganglia and thalamus;

- damage to the brainstem;

- increase the contrast of gray and white matter.

Four of the five criteria are sufficient for the

diagnosis [7].

Some patients develop hydrocephalus due to

compression of the Sylvian aqueduct; therefore these

patients require neurosurgical intervention [1—3, 8].

Clinical observation

We present the clinical case of the girl T., who first

came to the attention of neurologists and neurosurgeons

at the age of 2 months.

The child was from the first pregnancy, with urgent

delivery at 42 weeks, which proceeded on its own, without

complications. Body weight at birth, 3310 g, height,

53 cm. No anomalies were observed before the age of 2

months, the child grew and developed normally. At the

age of 2 months, preventive neurosonography (NSG)

was prescribed. At the time of the examination, the

mother had no complaints, noting only minor episodes

of the child's anxiety.

The results of the NSG are shown in Fig. 1. Frontal

standard projection. The arrows indicate cloudy

hyperechoic zones in the periventricular sections of the

anterior horns of the lateral ventricles. The ventricular

system is not enlarged. There is a narrowing of the

anterior horns of the lateral ventricles at the point of

contact with areas of increased echogenicity due to mass

effect of pathological foci.

Given the unusual nature of the NSG findings, were

in-hospital examination to clarify the diagnosis was

proposed to the parents. On June 28, 2011 the baby was

admitted to the nursing department. The NSG data were

regarded as possible ischemic lesion of the natal period or

expansive process. The child’s state drastically

deteriorated in the hospital: she lost ability to hold her

head, there were choreoid movements in the facial

musculature and athetoid movements in the distal parts

of the limbs, she suffered from expressed anxiety attacks.

On July 07, 2011 magnetic resonance imaging (MRI) of

the brain without contrast and with contrast enhancement

by Magnevist was performed. The results are shown in

Fig. 2 and 3.

In general, focal changes identified by MRI coincided

with those identified by NSG. A focus in the quadrigeminal

plate area is clearly visible. The beginning of


ventriculomegaly can already be clearly seen from these

pictures. The mass effect of pathological foci on the

anterior horns of the lateral ventricles is observed and its

lumen is practically invisible.

From July 26, 2011 there was further worsening of

the condition in the form of increase in anxiety, vomiting

and fits of “fading”. According to the NSG, there is a

progressive expansion of the ventricular system. On July

27, 2011, ventriculoperitoneostomy was performed. The

surgery had certain features dictated by the disease: due

to the narrowing of the anterior horns of the lateral

ventricles, caused by mass effect of the pathological foci,

it was decided to perform ventriculostomy not from the

Kocher point but through the horn (Dandy point) by

moving a catheter beyond the vascular plexus using

ultrasound control. Improvement was noted in the

postoperative period. General cerebral symptoms

regressed, hyperkinesis decreased. Genetic analysis

(genetic laboratory of the Russian Children's Clinical

Hospital, Moscow) revealed a mutation

Fig.1 Patient T. NSG at the age of 2 months.

Fig. 2. Patient T., age 2.5 months. MRI of the head without contrast enhancement in T1 and T2-modes. The primary lesion of the white matter of the frontal lobes with the involvement of the subcortical ganglia is visible. There is a moderate expansion of the lateral ventricles.


CASE REPORTS

c1117C>a(pClu373Lys) in the gene GFAP (Alexander's

disease), which is described in the mutation database

(cm023075) in the heterozygous state.

Later the child was observed by a neurologist and

received anticonvulsant therapy. A repeated in-depth

examination was conducted at the age of 3 years. The

general condition of the child was regarded as satisfactory.

There was marked delay in psychomotor development.

The child experienced epileptic seizures 1—2 times a

week in the form of a short-term “fading”. At the time of

the examination the child was sane, had speech at the

level of babbling, reacted to the examination positively,

could ‘fixate’ the eyesight, was interested in toys, took

them in hands and examined them for long time, sat

without support, did not walk. Exotropia. Choreoid-like

movements in the extremities. Pronounced muscular

hypotension.

MRI without contrast and with contrast enhancement

was performed. The results are shown in Fig. 4.

Discussion

This case is interesting in several aspects. Since the

first description of the disease back in 1949 and until

2011, there were less than 100 described cases, and only

ca. 50 of them were described with the use of modern

neuroimaging. In 2011, S.V. Serkov et al. [8] described

two cases of juvenile form of the disease for the first time

in Russia. Our case, perhaps, is the third case identified

in the Russian Federation.

We had a rare opportunity to obtain neuroimaging of

Alexander disease using NSG at the preclinical stage. It

should be noted that such NSG findings are difficult to

interpret, but they can point the clinician in the right

Fig. 3. Patient T., age 2.5 months. MRI of the head with contrast enhancement. Symmetrical accumulation of contrast in the frontal lobes, visual cusps and quadrigeminal plate.


Fig. 4. Patient T., age 3 years 2 months. MRI of the head. The condition after ventriculo-peritoneal bypass (VPS).a — MRI without contrast. The affected zones retain the former localization, but are less extensive. There are no indications of mass effect of pathological foci. The

luminaire of the anterior horns is visible together with the cavity of the transparent septum; b — MRI of the brain with contrast. There are not foci of contrast

accumulation.

a

b


CASE REPORTS

direction. Localization of foci in the frontal lobes with

spreading into the visual cups and their mass effect is

probably pathognomonic for Alexander's disease. We

have not found similar neurosonographic findings in the

literature.

The second important observation is the data

obtained with MRI with contrast enhancement. The

nature of the accumulation of contrast and the period of

the disease in which this accumulation occurs are

important. Intense accumulation of the contrast was

recorded in the lesions at the onset of clinical symptoms.

In addition to the intensity of contrast accumulation, the

symmetry of the foci is also notable. Another feature is

the lack of accumulation 3 years after the manifestation

of the disease during the stabilization period. It can be

assumed that the accumulation of contrast in the

leukodystrophy foci is typical for onset and height of the

disease, and that the period of remission can be

characterized by the absence of such accumulation. In

case of juvenile form of the disease described by S.V.

Serkov et al. [8], the intensity of contrast accumulation

was constant. The change in contrast accumulation

observed in our case has not been described in the

literature and may be characteristic of the infant form of

the disease.

During the manifestation of the disease, MRI

presentation fully complied with the criteria proposed by

Marjo S. van der Knaap et al. [7], however, during the

stabilization of clinical symptoms, no more than 3 out of

the 5 described criteria were present.

The third important fact concerns the course of the

infant form of the disease. The disease can last from

several months to 8 years. The average duration of the

disease is 2—3 years [8]. Our case demonstrates long

period of stabilization. It can be assumed that timely

shunt surgery in other cases can contribute to the

stabilization of the patient's condition and the

prolongation of his or her life.

Analysis of the described observations allows

proposal that there are distinct stages of the infant form

of Alexander's disease.

Conclusions

Focal changes detected in neurosonography in the

form of hyperechoic cloud-like foci that spread from the

periventricular sections of the anterior horn of the lateral

ventricles to the basal ganglia can be specific for the

infant form of Alexander's disease. Leukodystrophy foci

in the period of onset and height of the disease present as

mass process. Leukodystrophy foci identified during

MRI examination can intensively accumulate contrast

during the onset of the disease, and, on the contrary, do

not accumulate contrast during the period of the absence

of clinical manifestations, which may indicate the

presence of at least two distinct stages of the disease.

The infant form of the disease does not always lead to

a fatal outcome. At the same time, the severity of white

matter lesions inevitably leads to disability of the patient.

A timely shunt surgery is likely to prolong the life of these

patients.



REFERENCES1. Messing A, Brenner M, Feany MB, Nedergaard M, Goldman JE. Alexan-

der Disease. The Journal of Neuroscience. 2012 11 April;32(15):5017-5023.

doi: 10.1523/JNEUROSCI.5384-11.2012

2. Springer S, Erlewein R, Naegele T, Becker I, Auer D, Grodd W, Krägeloh-

Mann I. Alexander disease — classification revisited and isolation of a neo-

natal form. Neuropediatrics. 2000;31(2):86-92.

doi:10.1055/s-2000-7479

3. Vazquez A, Macaya N, Mayolas S, Arevalo MA, Enrıquez PG. Alexander

Disease: MR Imaging Prenatal Diagnosis. Case reporte. AJNR Am J Neuro-radiol. 2008 Nov;29(10):1973-1975.

doi: 10.3174/ajnr.A1215. Epub 2008 Jul 24

4. Ashrafi MR, Tavasoli A, Aryani O, Alizadeh H, Houshmand M. Alexander

Disease: Report of Two Unrelated Infantile Form Cases, Identified by

GFAP Mutation Analysis and Review of Literature; The First Report from

Iran. Iran J Pediatr. 2013 Aug;23(4):481-484.

PMID:24427505 [PubMed]

5. Kumar KJ, Suryaprakash H, Manjunath VG, Harsha S. Infantile Alexander

disease: a rare leukodystrophy. J Pediatr Neurosci. 2012 May;7(2):117-119.

doi: 10.4103/1817-1745.102573

6. Ozkaya H, Akcan AB, Aydemir G, Kul M, Aydinoz S, Karademir F, Suley-

manoglu S. Juvenile Alexander disease: a case report. Eurasian J Med.

2012;44:46-50.

doi: 10.5152/eajm.2012.10

7. Marjo S. van der Knaap, Sakkubai Naidu, Breiter SN, Blaser S, Stroink H,

Springer S, Begeer JC, van Coster R, Barth PG, Thomas NH, Valk J,

Powers JM. Alexander Disease: Diagnosis with MR Imaging. AJNR Am J Neuroradiol. 2001 Mar;22(3):541-552.

PMID:11237983

8. Serkov S.V., Pronin I.N., Bembeeva R.S., Kornienko V.N. Alexander’s Dis-

ease. Literature Review and Personal Observations. Luchevaya diagnostika and terapiya. 2011;4(2):17-32 (in Russ.).

The work is devoted to a rare genetic disease. The

observations are unique due to good neuroimaging of various

stages of the development of the disease and rare data of

neurosonography with the observed pathology. The literature

review cited by the authors in the discussion is also interesting.

Undoubtedly, the work is worthy of publication in the

neurosurgical journal, as it broadens the horizons of

Commentary

neurosurgeons in terms of differential diagnosis. In addition, as

the authors have shown, the presented disease sometimes

requires neurosurgical interventions to alleviate the patient's

condition.

Yu.V. Kushel (Moscow, Russia)



doi: 10.17116/engneiro201680690-97

Use of Surgical Approaches to the Posterior Cranial Fossa in Patients in a Lying PositionV.N. SHIMANSKIY1, V.V. KARNAUKHOV1, S.V. TANYASHIN1, V.K. POSHATAEV1,2, K.V. SHEVCHENKO1, D.A. ODAMANOV1, S.V. KONDRAKHOV2

1Burdenko Neurosurgical Institute, Moscow, Russia; 2Clinical Hospital №1 (Volynskaya) of the Presidential Administration of the Russian Federation, Moscow, Russia

Background. Various suboccipital approaches are extensively used in modern neurosurgery for treatment of posterior cranial fossa disorders. The main patient’s positions on the operating table during surgery are the half-sitting and lying ones.Material and Methods. The article provides a detailed description and the methodology of the suboccipital retrosigmoid and median suboccipital approaches in the lying position.Conclusion. The suboccipital retrosigmoid and median suboccipital approaches in the lying position, when used correctly, provide a good view of the operating field with the minimal risk of complications associated with the patient’s position on the operating table.

Keywords: suboccipital retrosigmoid approach, median suboccipital approach, posterior cranial fossa tumors, skull base surgery, skull base tumors.

e-mail: [email protected] © Group of authors, 2016

Various suboccipital approaches are extensively used

in modern neurosurgery to treat posterior cranial fossa

(PCF) pathologies, such as skull base, cerebellar, and

brainstem tumors, cranial nerve compression syndromes,

and vascular disorders of the vertebrobasilar basin [1—8].

The main patient's positions on the operating table during

surgery are the half-sitting and lying ones. Each of them

has its own advantages and drawbacks. The half-sitting

position ensures more adequate ventilation and provides

good visualization of the anatomical structures of the

posterior cranial fossa due to the natural passage of fluid

from the surgical wound under gravity. Meanwhile, this

position is associated with a high risk of air embolism and

hemodynamic disorders caused by shifting patient's

positioning (orthostatic hypotension), as well as results in

pneumocephalus and other complications. Air embolism

is the key life-threatening complication associated with

the semi-sitting position. It can result in severe

cardiovascular disorders, ischemic injury to cardiac muscle

and brain. These complications can be almost entirely

prevented if using the horizontal position [9]. This

circumstance makes many surgeons avoid using the semi-

sitting position for posterior cranial fossa surgeries. We

provide a detailed description and illustration to the

methodology of the main surgical approaches to the PCF

structures in the lying position.

Materials and Methods

More than 450 surgeries for PCF pathologies are

performed annually at the Department of Peri-brainstem

Tumors (Burdenko Neurosurgical Institute). The main

approaches used are the suboccipital retrosigmoid and the

median suboccipital approaches.

The suboccipital retrosigmoid approach (SRSA) has

been used by neurosurgeons for more than 100 years [1].

It is currently employed in surgeries of the following

PCF pathologies:

— tumors of the base of the PCF: neurinomas of

cranial nerves (auditory, germinal, and facial nerves and

the nerves passing in the jugular foramen area),

meningiomas, chordomas, etc.

— epidermoid cysts (cholesteatomas) of the

posterior fossa cisterns;

— syndromes of cranial nerve hyperfunction:

trigeminal and glossopharyngeal neuralgia, hemifacial

spasm, positional vertigo (the neurovascular conflict of the

vestibulocochlear nerve);

— tumors of the brainstem and cerebellar

hemispheres;

— vascular disorders of the vertebrobasilar basin.

For the lying position, a patient is placed in either

supine or lateral position.

Positioning the patient on the operating table in the supine position. A surgeon, a surgeon's assistant, and an

anesthetist are engaged in positioning the patient. The

anesthetized and intubated patient is lying in the supine

position, with his/her head secured with a head rest. While

the anesthetist slightly raises the patient off his/her

position, the surgeon's assistant places a roll under the

patient's ipsilateral shoulder, trunk, and the gluteal region,

thus ensuring a 30° angle. The surgeon rotates the patient's

head towards the trunk bending (Fig. 1a, b). The assistant

places a support into the ipsilateral shoulder to prevent the

patient from sliding as his/her position may be corrected

during the surgery by tilting the operating table (see Fig. 1a).

The anesthetist simultaneously bends the ipsilateral leg at

knee and hip joints to an angle of 30° and rotates it inward.


This ensures the required position of the body axis by

compensating for spine rotation around its axis as a roll is

placed. A foam pad is placed between the legs to prevent

soft tissue atrophy. The arm is placed on the patient's chest

ipsilaterally to the approach side. The surgeon and

surgeon's assistant perform head fixation using the

Mayfield skull clamp: while one of them holds the patient's

head raised, the other one places the pins. Pin positioning

is performed as follows: a single pin is ipsilaterally placed

onto the frontal protuberance, while the paired ones are

contralaterally positioned into the superior temporal line

and the occipital bone above the asterion (see Fig. 1a, b).

The pins are tightly secured in the outer table of skull; one

should avoid placing the pins above thin regions of calvarial

bones (above the frontal sinuses, mastoid air cells, and

along the anterior margin of the temporal muscle). Pin

position must provide an unencumbered view of the

operative field and leave a possibility for bone

skeletonization to a required extent.

The surgeon then rotates the patient's head secured

with the Mayfield–Kees skull clamp 30 degrees towards

the side contralateral to the pathological process and

maximally bends it forward , leaving no less than the

thickness of two transverse fingers between the patient's

chin and chest. One needs to make sure that the sagittal

suture is parallel to the floor (see Fig. 1a, b). This position

of the head ensures the best view of the structures of the

cerebellopontine angle. When rotating or bending the

head, it is also important to maintain the longitudinal body

axis (the line running through the external occipital protuberance and the apices of spinous processes of cervical

vertebrae must be straight). Allowance should be made for

the risk of compression of jugular veins associated with

excessive head flexion, which is particularly topical in

hypersthenic overweight patients having a short thick

neck.

Description of the surgical approach. The SRSA is

performed in the cervico-occipital region below the

superior nuchal line. Blood is supplied to this region from

the occipital and posterior auricular arteries. Blood

outflows from the soft tissues of the occipital region via the

veins accompanying the aforementioned arteries and

draining into the external jugular vein. Soft tissues of the

occipital region are innervated by the greater occipital

nerve accompanying the occipital artery [1].

The mastoid notch and the line of transition of the

occipital squama into the horizontal part are the landmarks

for incision of the soft tissues. In SRSA, skin incision is

often made parallel to the auricular concha, 1.5–2.5 cm

posterior to the mastoid notch (see Fig. 1d). The upper

one-third of the skin incision is made above the transverse

sinus projection line. The border between the middle and

the lower one-thirds of the incision runs at the level of the

mastoid notch (see Fig. 1d).

Once skin and subcutaneous fat were dissected,

muscles are transected at a point where they are attached

to the superior nuchal line and the occipital plane. It is

reasonable to perform the musclectomy stage using

Fig. 1. Suboccipital retrosigmoid approach in the supine position with a roller placed under the ipsilateral shoulder. a, b — positions of rigid fixation pins. The sagittal sinus is parallel to the operating room floor: 1 — the coronal suture; 2 — the sagittal suture; c — lateral view of the

positions of the patient and the rigid fixation system. Landmarks for skin incision (d): 1 — mastoid notch, 2 — incision running parallel to the auricular concha.



monopolar coagulation, which allows one to significantly

reduce capillary hemorrhage. The portion of the occipital

bone, from the mastoid process to the median line in a

medial direction (tentatively until the anticipated midpoint

of the cerebellar hemisphere is reached) and from the

superior nuchal line down to the foramen magnum, needs

to be skeletonized.

When dissecting the soft tissues, one should not forget

about the occipital artery whose injury causes profound

bleeding. It is reasonable to begin with identifying the

occipital artery in the soft tissues and to transect it only

after precoagulation. Skeletonization of the occipital

squama is typically accompanied by opening the emissaria

located lateral and superior to the mastoid notch and, in

the inferior regions, in the foramen magnum area. The

opened emissaria need to be sealed with wax.

Asterion, the point where the lambdoid, the

occipitomastoid, and the parietomastoid sutures meet, is a

landmark for making the burr hole. Transition between

the sigmoid sinus and the transverse sinus is located in the

projection of this point (Fig. 2a). The asterion most

typically lies 3—4 cm above the mastoid notch. The burr

hole is made 5 mm below the asterion. After dura mater is

separated from the bone around the burr hole, osteoplastic

trepanation is performed using a pneumatic trephine (see Fig. 2b). In some cases, when there is significant coherence

between the dura mater and the bone (which is often

observed in patients older than 60 years), resection

trepanation using bone-cutting forceps followed by closing

the bone defect with a graft is performed.

Special care is needed when cutting the bone above or

near the transverse and sigmoid sinuses, since injury to

these structures causes profound venous bleeding. The

injured sinus should be sealed with a hemostatic sponge or

the TachoComb material by placing them on the surface

of the injured sinus wall. By no way should the hemostatic

agents be placed into the cavity of an opened sinus, since

this may result in sinus thrombosis and severe neurological

deficit or even death.

In order to prevent injury to venous sinuses, the bone

should be cut 5 mm away from the tentative inferior border

of the transverse sinus and 5 mm medial to the sigmoid

sinus. The craniotomy is usually followed by additional

lateral resection of the bone to expose the margin of the

sigmoid sinus. Mastoid air cells often become opened as a

result of additional resection of the lateral margin of the

trepanation window. The disruption of their continuity

may cause nasal liquorrhea during the postoperative

period, which, in its turn, is associated with the risk of

meningitis. Therefore, they need to be sealed with

autotissue at the final stage of surgery. Adipose tissue

harvested from the patient's hip or fragments of muscle

tissue from the surgical wound on the neck can be used for

this purpose. TachoComb material or fibrin sealant can be

additionally used.

Most often, a trepanation window up to 4 cm in

diameter is sufficient for managing cerebellopontine angle

tumors. The borders of the trepanation window correspond

to the following structures: the upper border, to the inferior

margin of the transverse sinus; the lower border, to the line

of transition from the vertical portion of the occipital bone

to its horizontal portion; the lateral border, to the medial

margin of the sigmoid sinus; and the medial border, to the

midline of the cerebellar hemisphere [1]. Craniotomy size

varies depending on the type of the pathological process;

Fig. 2. Right-sided suboccipital retrosigmoid approach.a — schematic view of the main landmarks in the occipital region: 1 — coronal suture, 2 —superior sagittal sinus, 3 — confluence of sinuses, 4 — transverse sinus,

5 — lambdoid suture, 6 — occipitomastoid suture, 7 — asterion, 8 — mastoid notch, 9 — sigmoid sinus, and 10 — parietomastoid suture; b — general right-side view

of the craniotomy: 1 — transition from the transverse to the sigmoid sinus, 2 — projection of the sigmoid sinus (with a hemostatic sponge placed on it), and 3 — the

inferior margin of the transverse sinus.


however, visualization of the site of transition of the

sigmoid sinus to the transverse sinus is a prerequisite.

Lateral positioning on the operating table. The key

indication for this positioning is the hypersthenic body

habitus of a patient, namely, the short neck and broad

shoulders.

After the patient had been intubated, a surgeon and

surgeon's assistant roll him/her laterally onto one side

contralateral to the surgery side; the anesthetist is

simultaneously controlling the head position. Patient's

arms are secured using specialized holders (Fig. 3b, c); the

ipsilateral leg is bent at knee and hip joints to an angle of

30° and rotated inward. The surgeon's assistant places a

support under the lumbar region. Soft pads are placed

between the patient's legs and underarms to prevent soft

tissue atrophy. Maximum head flexion is achieved similar

to the position described previously; the distance between

the chest and chin is supposed to be equal to at least two

thicknesses of fingers in the transverse direction. The head

is then secured by the surgeon using a Mayfield skull clamp

(see Fig. 3a).

If needed, patient's shoulders can be stabilized using

adhesive tape (Fig. 4b). One should not forget about the

risk of stretch injury to the brachial plexus.

One should also bear in mind that the sagittal suture

must be parallel to the floor (see Fig. 3a). This head

position ensures the optimal approach angle for

manipulations within the cerebellopontine angle during

surgical intervention.

Description of the surgical approach

The landmarks for incision and the principles of

performing craniotomy are similar to those used for supine

positioning (see Fig. 2).

The median suboccipital approach. The key

indications for using the median suboccipital approach are

as follows:

— PCF neoplasms of median and craniovertebral

localization, including tumors of the fourth ventricle and

the brainstem;

— decompression of the craniovertebral junction in

patients with Chiari malformation and acute circulatory

failure in the brainstem; and

— vascular disorders of the vertebrobasilar basin.

Different positions on the operating table are used to

perform the median suboccipital approach in lying patients

are used: the prone and the three-quarter prone positions.

First, let us discuss the prone position, patient's

position on the operating table that is used most frequently

when performing this surgical approach.

Patient's position on the operating table. The patient is

intubated and anesthetized while lying on a patient

transport cart. Next, the surgeon and the surgeon's assistant

rotate the patient into the prone position onto the operating

table (the anesthetist is simultaneously controlling the

head position).

The patient is usually placed by rolling onto a

specialized foam frame, with its position controlled by a

nurse anesthetist (see Fig. 4a). The foam frame ensures

proper chest excursion during mechanical ventilation (see

Fig. 4a, 1). Additional corrugated foam rollers or underpads

are placed under the sites where the patient's body and

limbs may be subjected to positional compression (see Fig. 4a, 2). An additional roller can be placed under

patient's chest to ensure physiologically adjusted neck

flexion. The head is then secured with a Mayfield skull

clamp, with the longitudinal body axis strictly maintained.

The skull clamp pins need to be positioned in such a

manner as to ensure unencumbered view of the operating

field and leave a possibility for skeletonizing the occipital

bone to a required extent.

There are two modifications of the median suboccipital

approach: the inferior and the superior median approaches

(see Fig. 4c, d). The key difference is that both transverse

sinuses and the confluence of sinuses are exposed when the

superior median approach is performed (see Fig. 4d). The

foramen magnum and the arch of the C1 vertebra are not

affected by craniotomy performed through this

modification of the approach. In the case of the inferior

median approach, the upper border of trepanation runs

along the inferior margin of both transverse sinuses and the

confluence of sinuses until the foramen magnum, and is

accompanied by laminotomy of the posterior semi-ring of

C1 vertebra if necessary (see Fig. 4c).

The inferior median suboccipital approach is used

most frequently.

Description of the surgical approach. Skin incision is

made along the median line. It provides a minimally

invasive access to the target PCF structures.

The upper border of the incision lies 1—2 cm above

the external occipital protuberance (the inion); the lower

border lies in the projected point of the spinous process of

C3 vertebra (Fig. 5, a).

First, an incision of skin and subcutaneous fat is made.

A wound retractor device is placed, with its handle facing

upward. Dissection must be conducted along the cervical

white line in the avascular zone. The occipital arteries and

greater occipital nerves remain intact.

Once the soft tissues were prepared, the occipital bone

squama, the posterior arch of C1 vertebra, and the spinous

process of C2 vertebra are skeletonized. Deep cervical and

occipital muscles are separated from the nuchal line using

monopolar coagulation or a bone scraper and moved

downward and sideways.

Venous bleeding from the hypertrophied emissaria

may take place as the occipital bone squama is skeletonized.

In this case, they need to be closed with bone wax. When

skeletonizing the posterior semi-ring of C1 vertebra, one

should keep in mind the close proximity of vertebral

arteries that run in the posterior portion of the occipital

membrane. Bleeding from the venous plexuses of vertebral

arteries is stopped using hemostatic sponge.

Two burr holes are made below the inion, on both

sides from the external occipital crest (see Fig. 4c). "Pear-

shaped" craniotomy is then performed with a craniotome



(see Fig. 4c). If needed, the trepanation window can be

made wider: sideways to the maximum extent allowed by

the operating field and to the required extent, and

downward until the foramen magnum is reached.

Sometimes craniotome cannot pass through thickening in

the occipital bone near the margin of the foramen

magnum. This bone portion can be ground with a burr or

continue trepanation downwards and sideways using

bone-cutting forceps.

This approach can be either combined with

laminotomy of the posterior semi-ring of C1 vertebra

(see Fig. 5b) or performed individually. Indications for

laminotomy of the arch of C1 vertebra are determined by

pathology location, the degree of descent of the cerebellar

tonsils and, therefore, by the need to decompress the

craniovertebral junction and CPF structures. If

decompression of the craniovertebral junction is not

required, the posterior semi-ring of C1 vertebra is returned

to its original place and tightly secured with silk sutures.

The borders of laminotomy of the C1 cervical vertebra lie

no further than 1.5 cm sideways from the median line; i.e.,

its full absolute size is no more than 3 mm (see Fig. 5b) due

to the close proximity of vertebral arteries and the risk of

damaging them upon bone manipulation.

When performing the median suboccipital surgical

approach to a patient in the three-quarter prone position,

he/she is rolled sideways into the lateral position; the

patient's body is inclined by approximately 45 degrees.

Supports preventing trunk shifting with respect to the

operating table are placed at the level of the chest and

lumbar area. Patient's arms are secured with special

supports; the ipsilateral leg is bent at knee and hip joints to

an angle of 30° and rotated inward. Soft pads are placed

between the legs and in the underarm area to prevent the

development of soft tissue atrophy. The head is bent to a

maximum possible extent and then secured using a

Mayfield skull clamp (see Fig. 4b). Taking into account

the manipulation angle required to access the anatomical

structures of the fourth ventricular area and the

craniovertebral junction, no additional rotation of the

patient's head is required (see Fig. 4b).

Discussion

When choosing patient's position on the operating

table and performing the suboccipital approaches, a

number of questions may arise pertaining to the risks for a

patient, which are related only to his/her position rather

than to the existing neurosurgical pathology. Having

evaluated the experience of performing suboccipital

approaches to the patient in the lying and semi-sitting

positions that has been gained over the many years, we

have arrived at conclusion that performing these

approaches to the patient in the lying position is the most

safe procedure, since it allows one to avoid such life-

threatening complication as air embolism. An analysis of

200 vascular decompression procedures performed in

patients in different positions demonstrates that the semi-

Fig. 3. Suboccipital retrosigmoid approach in the lateral position. a — positioning of rigid fixation pins; b, c — patient's position on the operating table.


sitting position increases the risk of air embolism

25-fold [9]. Nevertheless, it is reasonable to use the

suboccipital approaches in some patients in the semi-

sitting position using intraoperative transesophageal

Doppler to control possible development of air embolism.

This category includes obese patients (in whom the lying

position blocks chest excursion), patients with giant-size

tumors and cervical osteochondrosis that prevents

adequate head rotation and/or flexion.

The use of the "lying" position makes it necessary to

accurately follow the landmarks when making a skin

incision and osteoplastic trepanation, since a deviation

from the trepanation performing standards narrow the

operating field and make the main surgical stage infeasible.

In its turn, this fact discredits the idea of using the lying

position that is safe if performed properly. Hence, when

using the suboccipital retrosigmoid approach, proper

mapping of the operating field ensures patient's safety.

The methods for sealing sinuses if damaged during a

surgery are often of concern. If a sinus was injured in the

"semi-sitting position", one should prevent the contact

between the sinus defect and air by all means, since the

sinus defect will become a source of air embolism in this

case. In this situation, a surgeon's assistant or a nurse must

continuously irrigate the sinus defect with normal saline

and subsequently seal its wall using a hemostatic sponge or

TachoComb.

Furthermore, a frequent question often is "what type

of trepanation should be performed, the resection or the

osteoplastic one?" When using the suboccipital

retrosigmoid approach, one should always prefer the

osteoplastic craniotomy. However, if pronounced

cohesion between the dura mater and the bone (especially

in elderly patients) is detected when a burr hole is drilled,

resection trepanation can be performed to avoid the

emergence of defects in the dura mater and sinuses; the

bone defect can be subsequently closed with a graft.

Osteoplastic trepanation should be preferred when using

the median suboccipital approach, excluding the cases

when decompression of the PCF structures are needed,

e.g., in surgeries for Chiari malformation [10].

Fig. 4. The lying position for performing the suboccipital median approach.a — prone position (Concorde position); b — three-quarter prone position; c, d — the modified median suboccipital approach; c — the inferior median suboccipital

approach. The arrows show the craniotomy borders: 1 — the sagittal sinus, 2 — the confluence of sinuses, 3 — the sigmoid sinus, 4 — C1 vertebral arch, d — superior

median suboccipital approach. The arrows show the craniotomy borders. The remaining notation is identical to that in Fig. 4c.



Conclusion

When used properly, the suboccipital retrosigmoid

and median suboccipital surgical approaches in the patient

in a lying position provide a good view of the operating

field, while leaving the risks of complications associated

with the patient's position on the operating table minimal.

A neurosurgeon must have a perfect command of these

7. Shimanskiy VN, Karnaukhov VV, Sergienko TA, Poshataev VK,

Semenov MS. Endoscopic assistance in vascular decompression of cranial

nerves. Voprosy neirokhirurii im. NN Burdenko. 2012;2:3-10. (In Russ.).

8. Shimanskiy VN, Karnaukhov VV, Sergienko TA, Poshataev VK,

Semenov MS. Endoscopic assistance in single-stage resection of posterior

cranial fossa meningioma and vascular decompression of trigeminal nerve

root. Voprosy neirokhirurii im. NN Burdenko. 2011;4:70-74. (In Russ.).

9. Israelyan LA, Shimanskiy VN, Otamanov DA, Poshataev VK, Lubnin AYu.

Patient's position on the operating table in neurosurgery: the sitting or lying

position. Anesteziologiya i reanimatologiya. 2013;4:18-26. (In Russ.).

10. Reutov AA. Principles of diagnosis and tactics of surgical management of

patients with type I Chiari malformation [dissertation]. Moscow; 2012. (In

Russ.). Accessed July 20, 2016.

http://medical-diss.com/medicina/printsipy-diagnostiki-i-taktika-

hirurg icheskogo-lecheniya-bolnyh-s-mal formats iey-kiar i- i-

tipa#ixzz4EvyZpoGT

Fig. 5. The inferior median approach.a — the landmarks for skin incision: 1 — the external occipital protuberance, 2 — the inferior incision line (the level of the spinous process of the C3 cervical vertebra);

b — the final view of the inferior median suboccipital approach: 1 — the occipital bone and the C1 vertebral arch were resected, 2 — additional lateral resection of the

occipital bone near the foramen magnum was performed using bone cutting forceps, and 3 — the anlantooccipital membrane is visualized.

REFERENCES1. Makhmudov UB, Shimanskiy VN, Tanyashin SV, Murusidze NA.

Suboccipital retrosigmoid approach. Voprosy neirokhirurgii im. NN Burdenko. 2001;3:25-28. (In Russ.).

2. Ribas GC, Rhoton ALJr, Cruz OR, Peace D. Suboccipital burr holes and

craniectomies. Neurosurgical Focus. 2005;19(2):1-12.

doi:10.3171/foc.2005.19.2.2

3. Rhoton ALJr. Cranial Anatomy and Surgical Approaches. Baltimore, MD:

Lippincott Williams & Wilkins. 2003;525-587.

4. Sekhar LN, Fessler RG. Atlas of neurosurgical techniques: brain. New York—

Sruttgart: Thieme Medical Publishing. 2006;860-870.

5. Shimanskiy VN, Karnaukhov VV, Odamanov DA, Kolycheva MV. Surgical

treatment of trigeminal neuralgia in patients with multiple sclerosis. Zhurnal nevrologii i psikhiatrii im. SS Korsakova. 2015;2:66-70. (In Russ.).

6. Poshataev VK, Shimanskiy VN, Tanyashin SV, Karnaukhov VV. The use of

endoscopic assistance in surgery of cerebellopontine angle tumors. Voprosy neirokhirurgii im. NN Burdenko. 2014;4:42-49. (In Russ.).

approaches. The proper use of the approaches ensures a

broad view of the cerebellopontine angle and the

craniovertebral junction area, while the traction of the

cerebral tissue is minimal and usually causes no

complications associated with their application.

Authors declare no conflict of interest.


The article by V.N. Shimanskiy et al. is highly relevant,

since the approaches being analyzed (the suboccipital

retrosigmoid and the median suboccipital approaches) are most

commonly used in surgical treatment of subtentorial

pathological neoplasms. While being rather simple, these

approaches ensure direct and the most convenient access to all

the posterior cranial fossa structures. However, only the

meticulous adherence to all the procedure nuances, starting

from proper patient positioning, allows one to achieve the

objectives of surgical management. It is the analysis of all

miniscule details of the aforementioned approaches that makes

this paper a thorough manual for using them in a patient in the

lying position. The criteria for selecting the patients for whom

these approaches are recommended were properly justified and

clearly stated. The authors placed special focus on prevention

of complications, in particular, postoperative liquorrhea.

Numerous schemes and figures that meticulously demonstrate

proper patient's position on the operating table as well as the

features of skin incision and skull trepanation are provided in

addition to description of the sequence of actions of an

operating surgeon.

This work is important, especially for young neurosurgeons,

since it teaches them how to perform a proper surgical approach,

which, along with good microsurgical skills, is a prerequisite of

successful surgery.

V.I. Smolanka (Uzhgorod, Russia)

Commentary


REVIEWS

doi: 10.17116/engneiro201680698-104

Navigation Systems in NeurosurgeryV.A. SHURKHAY1,2, S.A. GORYAYNOV1, E.V. ALEKSANDROVA1, A. SPALLONE2, A.A. POTAPOV1

1Burdenko Neurosurgical Institute, Moscow, Russia; 2Moscow Institute of Physics and Technology, Moscow, Russia; 3NCL-Neuromed, Department of Biomedical Sciences University di Roma Tor Vergata, Via Orazio Raimondo, Rome, Italy

When preparing the review, we analyzed publications available in the Medline database; a total of 1,083 publications related to the review's subject were analyzed. After more careful analysis, we selected 117 publications devoted to the development of neuronavigation in craniocerebral surgery, its historical background, current trends, and future prospects of the technique.

Keywords: neurosurgery, neuronavigation, stereotaxis, computer-assisted neurosurgery.


At the initial stage, the development of neurosurgery was

limited by technical level of that time. The lack of accurate and

objective anatomical assessment of the relationship between

paraplasm and surrounding structures in each individual

patient [1—3] was another major limitation. Fundamental

studies on the functional brain mapping, which were started as

early as in the XIX century by Broca, Wernicke, Exner, and

Dejerine, provided data on the architectonics of the key

functional systems and their topical representation in the

cerebral cortex [4, 5]. W. Penfield significantly contributed to

this work [6]. Nevertheless, it was difficult to assess the

individual characteristic features of the anatomy and

neurophysiology of each individual patient. There was an

urgent need to integrate these data and present them to

neurosurgeons. This problem could not be solved until 1970s

due to the absence of direct brain imaging methods, possibility

of mathematical processing and alignment of various data.

The instruments for frame-based stereotactic navigation

laid the basis for the development of neuronavigation systems.

In 1873, H. Dittmar et al. [7] used the instrument, which

provided approach to the neoplasms in the medulla oblongata

of laboratory animals for the first time in a neurophysiological

laboratory. The pioneering work of D.N. Zernov 1889 [8]

marked the beginning of stereotactic surgery on the human

brain. Further development of the method was associated with

the studies of Clarke and Horsley, who developed the device to

study the brain of monkeys of in 1906—1908. Ranson and

Ingram obtained basic information about the functions of the

reticular formation, hypothalamus, and midbrain, using

frame-based stereotaxis and modified Horsley-Clarke

apparatus [10]. Kirshner has overcome the difficulties of the

use of stereotaxis in humans associated with variability of the

relationship between the skull bones and brain structures,

which enabled thermal ablation of the trigeminal ganglion in a

patient with trigeminal neuralgia for the first time, using

originally designed stereotactic device [11]. In the second half

of the 1940s, E. Spiegel and H. Wycis [12] used the stereotaxic

atlas, which they previously developed, in combination with

the data of contrast ventriculography and position of the pineal

gland to localize intracranial anatomical structures and

describe the use of frame-based stereotaxis during neurosurgery.

L. Leksell significantly contributed to the development of

these techniques [13]. In 1949, he developed his own

construction of stereotaxic apparatus. Later on, J. Talairach,

E. Monnier, T. Riechertand, and F. Mundinger [14—16]

developed original stereotaxic devices for functional

interventions. The articles of Russian authors E.I. Kandel and

V.V. Peresedov [17—19] reported the results of the use of the

original stereotaxic apparatus in the cryosurgery of the

subcortical structures, as well as clipping of cerebral arterial

aneurysms.

The development of X-ray diagnostic technique

significantly expanded the possibilities of neurosurgical

pathology diagnosis. In 1908, F. Krause et al. [20] devoted a

separate chapter of their multi-volume neurosurgery guide to

radiodiagnosis of neurosurgical diseases and identified

characteristic features of some of them. The development of

pneumoventriculography was the next milestone [21]. The

capabilities of the contrast cerebral angiography proposed by

E. Moniz [22, 23] greatly improved neurosurgeon’s knowledge

about the individual anatomy and pathological anatomy of

patient’s cerebral structures.

The use of metabolic navigation was based on the discovery

of the phototoxicity phenomenon in the early XX century and

was associated with the studies of Raab and von Tappeiner

[24]. In 1924, Policard showed that some malignant human

tumors fluoresce in the orange-red spectral range when

irradiated with ultraviolet light [25]. This effect is due to the

formation of endogenous porphyrins in tumors, which have

been confirmed by fluorescence of experimental tumors in the

red spectral region in animals pre-administered with

hematoporphyrin [26]. The first study on the use of fluorescein

dye during neurosurgical operations in patients with brain

tumors was published by G. Moore in 1947 [27]. Fluorescein is

not widely used in neurosurgical practice due to its toxicity and

low specificity of the method. The paper of B.A. Samotokin et

al. [28] reported the use of organic dyes for intraoperative

imaging of brain tumors. F.A. Serbinenko et al. [29] used the

technique of superselective intravascular injection of dyes in

tumor-supplying vessels. However, this method cannot be

used in routine practice due to insufficient specificity and

reproducibility of the results and toxicity of preparations.

Since the mid-1990s, idocyanin green dye, which is

fluorescent in the infrared range, is used for intraoperative

visualization of blood vessels (both in normal brain tissue and

in tumors). The possibilities of modern surgical microscopes

(e.g., Zeiss OPMIpentero) enable color mapping, determining

the direction of blood flow [30, 31].

Pioneering studies of the metabolism of porphyrins and

visualization of leukemic cells using 5-aminolevulinic acid

were reported by Z. Malik et al. [32] in 1979. It was shown that

5- aminolevulinic acid is metabolized by enzyme systems that


are active only in tumor cells to produce protoporphyrin IX,

which is fluorescent under external light source having certain

wavelength [33]. In the late 1990s, the first reports on the

possibility of using 5-aminolevulinic acid in neurosurgery were

published [34]. Later studies showed that the use of metabolic

navigation improves the extent of tumor resection and

increases disease-free and overall survival of patients with

malignant gliomas [35]. The studies of A.A. Potapov et al.,

S.A. Goryaynov et al. [36, 37] have shown that metabolic

navigation using 5-aminolevulinic acid can be applied not only

in gliomas, but also in meningiomas. Currently, the ways to

improve sensitivity of fluorescence diagnosis in the surgery of

low-grade gliomas and metastases are being investigated [36,

38]. In the absence of visible fluorescence, the authors

suggested laser spectroscopy method to estimate the

concentration of amino-levulinic acid in the tumor tissue and

thus differentiate it from the healthy brain [24, 37, 38].

Along with fluorescence, high resolution mass

spectroscopy is another promising method for ultrafast real-

time intraoperative identification of tissues. The method

provides molecular “fingerprints” based on the analysis of

lipids and proteins produced in the ionization mass spectra,

which enables characterizing various brain tumor [39].

Radioisotope-based diagnostic techniques are being used

since the mid 1950s — early 1960s [40]. Various isotopes were

used, such as iodine(111I,123I,125I), bismuth, mercury, gold,

technetium, copper, and labeled serum albumin [41]. In 1964,

the article of E.V. Kotlyarov [42] reported the results of the use

of radioactive phosphorus for intraoperative localization of

brain tumors. The study of M. Fischer et al. [43] published in

1977 showed that radioangiography is more sensitive than

scintigraphy, when determining the histological structure of

the tumor. At the same time, the latter enables more reliable

assessment of tumor vascularization. The study of A.N.

Konovalov [44] published in 1980 notes very high sensitivity of

perioperative beta-radiometry, which enabled tumor

localization in 98% of cases. Later studies showed that positron

emission tomography with 11C-methionine involved in the

metabolic pathways in tumor cells is more specific for glial

tumors. The data on the accumulation of methionine enable

determining the degree of anaplasia, selecting the target for

stereotactic biopsy, differentiating between radiation necrosis

and continued tumor growth, developing a predictive model

for the patient [45, 46]. F.M. Lyass and E.Ya. Shcherbakov

[47—49] investigated the role of radionuclide studies in the

diagnosis of CSF system diseases, intracranial inflammation,

and the consequences of traumatic brain injury. Currently,

single-photon and positron emission tomography are mainly

used for differential and topical diagnosis of various

pathological processes; these methods have significant

limitations [46] in intraoperative navigation.

X-ray computed tomography (CT) is based on the studies

of Oldendorf, Hounsfield, and Cormack. The first ever in vivo

image of patient's brain was obtained in 1972 [50, 51]. In 1976,

L. Jacobs et al. [52] compared the results of computed

tomography and 79 autopsies, the accuracy of intracranial

pathology diagnosis was 86.2%. Today, CT with intravenous

contrast and perfusion techniques enable assessing the

condition of the blood flow in the mass lesion and perifocal

zone in different parts of the brain, including its deep structures

and brainstem [53—57]. The study of J. Maroon et al. [58]

focusing on the use of CT to navigate the puncture emptying of

tumor cysts and brain abscesses was an important milestone in

neurosurgery. In 1979, R. Brown [59] presented the results of

successful use of CT and three-dimensional computer graphics

for stereotactic localization of targets in a phantom with

installed special stereotactic frame. Later on, the results of

clinical application of CT to calculate stereotactic surgery

(functional neurosurgery and tumor biopsy) were reported in

the articles of J. Boethius, B. Czerniak, and Z. Krzystolik

[60—62].

Intraoperative CT was developed in various fields of

neurosurgery to specify the completeness of tumor resection,

eliminate intraoperative complications, intraoperatively

correct navigation information, and provide more accurate

implantation of stabilization system elements in spinal

neurosurgery [63—66].

The studies of F. Cope and R. Damadian [67], who used

magnetic resonance to determine the concentration of

potassium ions in a bacterial cell in 1970, provided the basis for

magnetic resonance imaging (MRI). Obtaining information

about tumors in vivo was made possible through the use of a

field-focusing nuclear magnetic resonance, FONAR [68]. The

first magnetic resonance image of the human chest was

obtained in 1977 [69]. The first commercially available

magnetic resonance imager (MRI) was produced in 1980 [70].

When comparing CT and MRI for stereotactic interventions,

W. Birg et al. [71] noted high accuracy of the latter, better

visualization of brain structures located close to the bone

tissue, as well as the absence of necessity for contrast

ventriculography during functional operations.

Intraoperative MRI also enables intraoperative correction

of navigation data and improves the completeness of surgery.

However, it requires special equipment in the operating room,

non-magnetic devices and instruments [72]. Low-field

portable MR scanners require longer scan time due to low

resolution, which lengthens the operation time and does not

enable perfusion or spectroscopic studies during the operation.

High-field MRI scanner, providing better image quality and

wider visualization capabilities due to larger number of

sequences, are difficult to integrate into existing operating

rooms, requiring either major modernization of the operating

unit or its reconstruction with allowance for MRI placement.

In addition, the use of high-field scanners is associated with

image artifacts and requires long-term personnel training.

Furthermore, intraoperative use of CT and MRI is very

expensive and it is not available in all hospitals.

Intraoperative use of ultrasound (US) is the most available

and simple method for navigation and localization of

neoplasms and correction for brain displacement [73].

Application of three-dimensional US-navigation, such as

Sonowand Invite system, improved surgeon's orientation,

provided adequate assessment of the completeness of

paraplasm resection and identification of intraoperative

complications, including those in ventriculoendoscopic

surgery [74—76]. Along with Sonowand system, a combination

of a separate expert-level ultrasonic scanner, control computer,

and neuronavigation system were used for intraoperative

three-dimensional US-scanning and navigation [77, 78].

The effect of brain displacement reduces the accuracy of

intraoperative navigation [79, 80]. Reliable prediction of the

magnitude and direction of brain displacement is not possible

[81]. Correction for brain displacement can be achieved using

intraoperative computed tomography or MR imaging, as well

as ultrasound study.

The development of neuronavigation systems, which

made all of the above methods as much applicable as possible

from the neurosurgeon’s viewpoint, was the logical


REVIEWS

continuation of the studies of intraoperative visualization of

paraplasms and other brain lesions. Currently, the most

accurate and sparing approach to the pathological lesion is

possible in each particular patient.

Since the inception of neuronavigation systems, they

developed along two parallel lines determined by the used

monitoring techniques, optical (active or passive) or

electromagnetic.

In the first report of A. Kato et al. [82] on the frameless

electromagnetic navigation, the system which enables

monitoring of inclination and spatial arrangement of the

surgical instrument equipped with electromagnetic sensor to

within 4 mm was described. ISG Magic Wand system produced

in 1992 was the first commercially available neuronavigation

system. It was a manipulator consisting of six segments, where

a special pointer, rigid endoscope, or biopsy needle can be

installed. This system was used for navigation in brain tumors,

epilepsy surgery, ventriculoscopic operations, stereotactic

biopsies, pathology of the skull base, posterior fossa, clivus,

and superior cervical vertebrae [83—85]. This system could not

be used for functional neurosurgery due to inability of rigid

fixation of navigation manipulator and relatively high

error (>2.2 mm) [86].

The operation principle of electromagnetic navigation systems is based on the fact that a special generator (running on

DC or AC) creates an electromagnetic field around the

patient's head, which is the coordinate system where the

reference and surgical instrument equipped with a built-in

electromagnetic sensor or special adapter are positioned.

Spatial movement of the sensor changes the characteristics of

the field at this point, which allows the navigation system to

determine the coordinates of the instrument. The dimensions

and placement of the sensor on the instrument may vary,

affecting the functionality of the system: for example,

Medtronic Stealth Station 7 navigation system (Medtronic,

USA) incorporates a separate external electromagnetic

navigation module and DC electromagnetic field generator;

sensors in disposable instruments are located in the handle,

which prohibits changing the length of the instrument during

the operation or its bending. At the same time, Fiagon

navigation system (Fiagon GmbH, Germany) include

electromagnetic field generator operating on alternating

current, and instruments contain two sensors: one of them is

located on the working end of the instrument and the other is

located on the handle, which allows the surgeon to model

(bend) the instrument depending on the operating situation,

while preserving navigation accuracy. Application of direct

current to generate electromagnetic field is an earlier

technology. It requires the use of larger sensors and the

resulting field is more vulnerable to various factors that can

change its shape, such as the presence of large quantities of

metal or a source of electromagnetic interference near the

patient's head [87]. Using AC overcomes these limitations

[88]. Electromagnetic field generator can be fixed to the

operating table using a special bracket (Stealth Station 7,

Fiagon), as well as integrated into the universal head support

for an operating table (Fiagon). A separate module for

electromagnetic navigation that requires connection to the

main system increases the overall size and floor space occupied

by the system. The advantages of the last generation

electromagnetic navigation system include their portability

and compactness, the possibility of integration into existing

operating room system, very small sensor, which enables its

integration into an instrument without increasing its size and,

more importantly, changing tool geometry during operation

without loss of navigation accuracy. According to C. Hayhurst

et al. [89], the use of electromagnetic navigation in most cases

enables avoiding rigid fixation of patient's head, for example,

during neuroendoscopic interventions, bypass surgery, awake

craniotomy. Compatibility with intraoperative

neurophysiological monitoring is an important factor.

The use of the most portable and mobile electromagnetic

navigation systems, which are not only a module in the basic

optical navigation system, but rather can be effectively

integrated into the workspace of the operating room, do not

require any special infrastructure owing to full compatibility

with existing equipment and instruments, and are easy to

master for the staff, is the most promising direction.

Most neuronavigation systems developed in the 1990—

2000s were based on optical monitoring technique. Historically,

its earlier version involves the use of diodes emitting light in

the IR range, which is detected by the receiving camera of the

system. The LEDs are located on the reference, which is

placed as close to the patient's head as possible. They form the

basis of the coordinate system and can also be placed on the

instruments using special adapter or directly integrated into

the instruments. Passive techniques involve the installation of

reflective spheres, which are located in the field of view of the

camera equipped with an infrared light source, on the

reference, instruments, and adapters. The article of K. Roessler

et al. [90] describes the results of clinical application of this

system in spinal and cranial neurosurgery. System accuracy

averaged 3.4 mm in 36 craniotomies and 11.3 mm in 4 cases of

spinal operations. The large error during spinal operations was

associated with difficulties in the registration of images and the

use of cutaneous registration markers. The development of

computer graphics and new data processing capabilities have

led to the use of “augmented reality” concept in neurosurgery,

which enabled direct real-time alignment of paraplasm

modeling results, functional areas, and anatomical landmarks

(based on CT or MRI data) with the surgical field [91].

New features of intraoperative neuronavigation were

associated with combining different modalities of

neuroimaging: CT, conventional MRI, diffusion-tensor and

functional MRI, as well as magnetoencephalography and

electrophysiological mapping of speech, sensory, and motor

areas of the cerebral cortex [92]. This improved the results of

surgical procedures for pathological processes at the functional

areas, hydrocephalus, ventriculoendoscopic interventions,

and epilepsy [93, 94]. Many authors noted a positive effect of

intraoperative navigation on completeness of paraplasm

resection, duration of hospital stay, overall survival, and

functional outcome [95—97].

The use of data provided by diffusion-tensor MRI,

magnetoencephalography, functional MRI in a navigation

system with simultaneous recording of cortical somatosensory

evoked potentials enabled successful reconstruction of

conductive paths of the brain at different levels and assessing

the impact of the pathological process on these pathways [98,

99]. Computer modeling facilitated understanding of the

anatomical relationships between the paraplasms and intact

structures of the brain [100]. The use of neuronavigation

significantly improved the resolution of transcranial magnetic

stimulation [101].

Comparative analysis of various neuronavigation system

(ISG Magic Wand, Cygnys PFS, SMN) by E. Benradette et al.

[102] in the laboratory showed that, regardless of the used

technique (mechanical manipulator, electromagnetic or


optical monitoring, respectively), the average precision of the

systems did not differ significantly and ranged 1.67 to 2.6 mm.

According to the authors, selection of navigation system was

mainly determined by portability, ease of use, and compatibility

with the operating microscope. The study of M. Cartellieri et

al. [103] comparing six different navigation systems also

showed no fundamental difference between the systems, since

their precision was comparable (error ranged 0 to 6.7 mm). For

a long time, precision of neuronavigation systems compared to

conventional frame-based stereotactic devices was the subject

for discussion. R. Steinmeier et al. [104] analysed the factors

(technical precision of the system, registration process, voxel

size and/or the presence of images distortions, intraoperative

situation) that have a direct impact on navigation precision. It

has been shown that imaging modality has minimal effect on

the accuracy of navigation. The number of registration markers

and the nature of their placement are the most important

factors. The authors concluded that the accuracy of

neuronavigation systems (as exemplified by a robotic

microscope MKM Carl Zeiss and optical system Stealth

Station Sofamor-Danek) is comparable to that of conventional

stereotactic frame-based devices. Particular attention was paid

to the fact that registration error calculated by each navigation

system does not reflect the real error. U. Spetzger et al. [105]

analyzed 10 years of experience in the application of

neuronavigation and came to conclusion that system accuracy

is mainly affected by the human factor. At the same time, S.

Poggi et al. [106] concluded that the parameters of CT or MRI

images also have an impact on the accuracy of neuronavigation.

The accuracy of target localization based of CT data was higher

than when using MRI data; the presence of image distortions

was an important parameter that reduces the accuracy of MRI

navigation. At the same time, Y. Enchev et al. [107] found no

statistically significant differences in accuracy of

neuronavigation with CT and MRI. There was also no

significant differences in the navigation accuracy when using

registration based on anatomical landmarks or fiducial

markers. For this reason, W. Pfisterer et al. [108] recommended

to use registration based on anatomical markers as more

economic and less costly.

Comparative analysis of systems with active (Stryker) and

passive (BrainLab Vector Vision) tracking technology

conducted by D. Paraskevopoulos et al. [109] at the

anthropomorphic model of the head showed that the accuracy

was similar for both systems (<1.5 mm), and accuracy data

calculated by the systems do not always fit the actual values

and always require rechecking by surgeon. In all options,

optical technique is characterised by following limitations: a)

the need for placing the camera at a distance of at least 1 meter

from the spheres or diodes; b) placing the camera on a separate

bracket or stand, increasing the size of the system and reducing

its portability and mobility; c) dependence of navigation

accuracy on the state of reflecting spheres or diodes; d) “visions

line” problem of the camera, leading to cessation of navigation

when closing diodes or spheres with some object; e) bulky

adapters for reflective spheres or diodes to be mounted on

surgical instruments; e) inability to provide navigation of

instrument with variable length, curvature, or made of soft

materials (silicone catheters); f) the need for rigid fixation of

patient's head, which limits the use of navigation in children

[110]. It was also shown that infrared radiation from the optical

navigation system tracker camera can substantially affect the

performance of pulse oximeters, causing errors in the quality of

signal and assessment of saturation level [111]. In 2001,

M. Zaaroor et al. [110] published the paper, where the

experience with electromagnetic navigation system Magellan

(Biosense Webster) was analyzed. The electromagnetic sensor

was located at the working end of the instrument, which

enabled using the system for installation of flexible catheters,

navigation of endoscopes and other instruments.

The advantages of the use include high operation speed,

high precision, small size, the possibility to navigate flexible

instruments, greater freedom of movement of the surgeon,

which does not depend on the viewing field of the recording

camera, no need for rigid fixation of the head, which enables

operating children from the second week of life [110, 112,

113]. At the same time, T. Rodt et al. [114] noted that the

interference of the magnetic field might affect the performance

of the navigation system.

Comparative analysis of the accuracy of optical and

electromagnetic navigation systems conducted by J. Rosenow

et al. [115] revealed no significant differences (the target point

location error ranged 0.71 to 3.51 mm). A. Sieskiewicz et al.

[116] also compared optical and electromagnetic navigation

systems (Medtronic Stealth Station and Digipointeur,

respectively) and concluded that electromagnetic navigation is

faster and easier to configure, provides greater freedom of

surgeon’s hands, and its accuracy is similar to that of the

optical system; the small number of instrument supported for

navigation was the imitation of that specific electromagnetic

system.

Recently, intraoperative robot assistance became one of

the main trends in surgery, improving safety and accuracy of

surgery due to high-precision intraoperative navigation. In

neurosurgery, such systems have been tested in preserving

craniotomy, precise approach to deep brain structures for the

purpose of biopsy of tumors, inflammatory and other lesions,

implantation of shunt systems, electrodes and others. [117,

118]. Robotic systems are essentially a further option of the

development of navigation systems.

ConclusionThe analysis of the literature over the past 100 years

revealed preconditions for the development of neuronavigation

and traced the evolution of this trend from both technical and

clinical point of view. The advantages of using navigation

systems in modern neurosurgery are obvious. Neuronavigation

is one of the most popular high-tech methods, which enables

combining various studies to evaluate the anatomical and

functional situation in the preoperative and intraoperative

periods. All this enables conducting highly accurate and safe

surgical procedures much faster than conventional methods.

Application of neuronavigation systems is highly valuable from

both clinical and scientific viewpoint. Integrative nature of

neuronavigation enables combining different modalities of

data, including anatomical, neuroimaging, molecular, and

neurophysiological, which improves the efficiency,

effectiveness, and conclusiveness of clinical studies carried out

using this technique. Furthermore, it is undoubtedly highly

promising as an educational method. Currently,

neuronavigation should not be a luxury for neurosurgical

clinics; its application should be as widespread and routine as

possible. We believe that, although neuronavigation does not

replace the expertise and clinical thinking of neurosurgeon, it

is a necessary complement, which enables neurosurgeons to

maximize the use of their skills.


REVIEWS


The article was supported by the grant of the Russian

Scientific Foundation 16-1510431 “The development of

methods and approaches for automated identification of brain

tumor tissues using multidimensional molecular profiles

database as the main element of data processing system of the

intelligent neurosurgical scalpel”.

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doi: 10.17116/engneiro2016806105-107

Prevention and Treatment of Postoperative Epidural Scar AdhesionsD.M. ZAV’YALOV, A.V. PERETECHIKOV

Navy Clinical Hospital 1469, Severomorsk, Russia

Postoperative epidural scar adhesions remain one of the most common late complications of microdiscectomy, which worsens the overall outcome in treatment of herniated lumbosacral discs. Despite a large number of conservative and surgical treatment options for epidural scar adhesions, the treatment outcome not always satisfies patients and doctors. The review was aimed at systematizing the available data on this complication and facilitating the choice of appropriate treatment strategy.

Keywords: epidural scar adhesion, epidural fibrosis, microdiscectomy, disc herniation, degenerative disc disease.

e-mail: [email protected]© D.M. Zav'yalov, A.V. Peretechikov

Despite the development of new techniques and

achievements in the surgical treatment of herniated discs, the

number of poor postoperative outcomes in the form of persistent

radicular pain syndrome still remains high and accounts for

5—20% according to different authors [1—4].

The development of adhesive process known as epidural

scar adhesions or epidural fibrosis is the most common cause of

persistent radicular pain syndrome. The incidence of epidural

scar adhesions among the other reasons of so-called “failed

back surgery syndrome” is up to 8—70% [3, 5—9].

The causes of excessive formation of connective tissue in

the epidural space after surgery are still not fully understood. It

is still not clear, why the pronounced epidural fibrosis develops

in the postoperative period in some cases, while it is less

pronounced or absent in other cases under identical conditions.

The relationship between the severity of epidural fibrosis

and discectomy technique still remains a debatable issue.

Several authors suggest that the incidence of this postoperative

complication is lower in the case of minimally invasive

interventions, application of gel materials and insulating

membranes, various surgical techniques preserving ligamenta

flava, and intraoperative irrigation of nerve structures with

steroidal and non-steroidal anti-inflammatory drugs. In the last

few years, there were publications describing the prevention of

scar-adhesions in the following way: the affected root and dural

sac at the area of surgical trauma are enveloped with fat injected

with methylprednisolone solution. The experimental studies

showed that this method reduces the activity of prostaglandins

E1 and E2 and leukotriene B, which are the triggering factor in

the development of peridural fibrosis. There are significantly

different opinions on the effectiveness of this method. Some

authors [3, 5, 10—15] believe that it is useful; on the contrary,

others believe that it increases scarring.

Many authors [16—21] believe that immuno-infiltrative

aseptic inflammation form the basis for discogenic epidural scar

adhesions, others note the important role of preoperative values

of fibrinolytic activity of the blood in the development of

epidural fibrosis, since decrease in fibrinolysis and anticoagulant

mechanisms and increase in blood coagulation in the

preoperative period increase the risk of epidural scar adhesions

[6, 22, 23].

Pain syndrome caused by the development of epidural

fibrosis is not characteristic of the early postoperative period,

and patient’s quality of life worsens due to persistent pain

caused by fibrotic changes in the epidural space only 2—18

months after discectomy [6, 24, 25].

Clinical and neurological examination, including medical

history, local status, and neuroimaging techniques is the main

diagnostic method to verify the postoperative epidural scar

adhesions. Magnetic resonance imaging (MRI), whose

effectiveness is improved when using contrast enhancement

(Magnevist, Gd-DTPA), is the most popular and informative

imaging technique [26—32]. Electrophysiological methods of

investigation (somatosensory evoked potentials,

electroneuromyography) are no less informative [33].

Despite the fairly large number of treatment methods for

epidural fibrosis after microdiscectomy, most authors [34—37]

note that all of them lack clinical effectiveness. General

treatment regimen should be based of general principles of

vertebral pathology treatment, including pathogenetically

oriented complex and stage-by-stage sparing therapeutic

modalities with allowance for the individual characteristics of

patients [28].

Medicinal treatment with nonsteroidal anti-inflammatory

drugs was suggested as a conservative treatment, limiting the

development of fibrous tissue in the postoperative period [38—

40]. According to some researchers [41], the use of

corticosteroids for the purpose of anti-inflammatory therapy in

the treatment of epidural fibrosis is well founded. In the case of

persisting long-term intractable pain syndrome caused by

epidural fibrosis, epidural block is effective [42, 43].

Physiotherapy (amplipuls, magnetotherapy, electrophoresis

with caripazim) is widely used as the non-drug treatments for

pain [44]. Outcomes of reoperations carried out due to

ineffective conservative therapy do not always satisfy patients

and surgeons [45, 46].

Epidural scar adhesions are still quite common in today’s

neurosurgical practice. It is highly significant medical and

social problem: recurrence of radicular pain in the postoperative

period makes patients to feel desperate, destroying their social

adaptation. The need for timely treatment and prevention of

epidural scar adhesions is undoubted and dissatisfaction with

clinical outcomes makes it a pressing problem.

There is no conflict of interests


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Literature review “Prevention and treatment of

postoperative epidural scar adhesions” focuses on the topical

problem: scarring processes, developing after neurosurgical

interventions for spinal pathology, in particular after

microsurgical discectomy. It is well known that these processes

to some extent develop in all the operated patients and can

significantly reduce patient’s quality of life and even destroy the

results of formally successful surgery. The authors present data

on the importance of epidural scar adhesions in the development

of neurological symptoms, summarize the data obtained from

Russian and international literature on the diagnosis and

possible methods to prevent these processes.

Given the complexity and multidimensionality of these

problems, it would be interesting to determine risk factors for

adhesive processes in the case of decompressive and stabilysing

interventions, including their relationships with the type and

extent of stabilizing structure. The authors rightly pay attention

to MRI and contrast-enhanced MRI in the diagnosis; it would

be useful to mention the role of other techniques, such as

percutaneous minimally invasive diagnostics, in particular

flexible endoscopy (epiduroscopy and thecaloscopy). Among

possible prevention methods, the use of type 3 collagen, and,

more importantly, limited aggressiveness of discectomy, in

particular by applying portal endoscopic techniques, are worth

noticing.

A.O. Gushcha (Moscow, Russia)

Commentary

· ISSN 0042-8817 (Russian ed. Print) ISSN 2313-8254 (English ed. Online) ISSN 2309-1681 (Russian...

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