1Management of Trigeminal Neuralgia

DR PRAVEEN K TRIPATHI

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“ …. as it were a flash of fire all of a sudden shot

into all those parts …. which made her shreeke out…”

Letter to a friend by John Locke December 4, 1677

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2nd Century – Aretaeus of Cappodocia in “Cephalaea”.

1037 AD – Avicenna.

1677 – John Locke first description.

1756 – Nicolas Andre – “tic douloureux” “Cynical spasm”.

1773 – John Fothergill – “Fothergill’s Disease”

1829 – Bell – Anatomy of 5th nerve

HISTORICAL PROSPECTIVE

1853 – Trousseau – “ Neuralgia epileptiform” 1942 – Bergouignan – Phenytoin 1962 – Blom – Carbamazepine 1934 – Dandy – Vascular compression of nerve 1967 – Peter Jannetta devised MVD1998 - Khan—Gabapentin, for frequency rhizolysis, trigeminal neuralgia in temperature monitoring, multiple sclerosis2007 - Obermann—Pregabalin

HISTORICAL PROSPECTIVE

5Anatomy

Origin – Gasserian ganglion Upper Ventral Pons

4 Nuclei – Principal Sensory

Motor

Spinal

Mesencephalic

3 roots –Portio Major – 125,000 fibers – 50% unmyelinated

Portio Minor – 3000 – 7500 fibers – 20% unmyelinated

Intermediate

3 divisions + 3 autonomic ganglia

Ophthalmic Ciliary

Maxillary Sphenopalatine

Mandibular Otic 4-May-16

6Anatomy

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7 Trigeminal ganglia

Covering –contained in a dural pouch known as cavum trigeminale(menkel,s cave)

Dural extend forward as a ballooning of meningeal layer of dura mater from posterior cranial to middle cranial fossabelow attached margin of tentorium cerebelli

Cavum-

Roof-formed by two meningeal layer

Floor-one meningeal and one endosteal layer

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8Definition

Trigeminal Neuralgia is a clinical syndrome distinguished by brief paroxysms of Unilateral, lancinating facial pain in the 5th nerve distribution triggered by cutaneous stimuli, such as a breeze on the face, chewing, talking or brushing the teeth.

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Epidemiology

Incidence, approximate at 5 in every 100 000 Gender ratio of female : male = 2:1 Right sided 56% of the time Maxillary (V2) > Mandibular (V3) > Ophthalmic (V1) Mean age at diagnosis is 60 years-old It occurs mostly after 5th decade.↑ frequency with age,

highest at >80 years old 10-15% of patients seeking care at dental specialty 4-May-16

10Etiology of TGN

Medical: MS, Charcot Marie Tooth disease, Lyme disease, infarct, Rhombencephalitis . Surgical: 1. Vascular Compression - Superior Cerebellar artery. Anterior inferior cerebellar artery Pontine perforator from basilar Petrosal Vein Vertebrobasilar Dolichoectasia 2. Other Vascular Lesions - AVM Aneurysm

3. Tumors - Schwannoma Meningioma Epidermoid Lipoma Metastasis

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11Etiology and Pathophysiology….

Older ideasEpileptogenesis (seizures from the brain)Newer theoriesEctopic nerve firing (seizures in the nerve)Ephapsis (cross-wirednerves)

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12Etiology and Pathophysiology….

• Demyelinative lesions of trigeminal fibers appear to set up ectopic generation of spontaneous nerve impulses and their ephaptic conduction to adjacent fibers. (Gardner)

• This can lead to pain attacks at the slightest stimulation of any area served by the nerve .

• It also hinder the nerve's ability to shut off the pain signals after the stimulation ends

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13PATHOPHYSIOLOGY

Chronic irritation of

the trigeminal

nerve

failure of segmental

inhibition in the trigeminal nucleus, and

ectopic action potentials in the

trigeminal nerve.

increased firing and impaired

efficiency of inhibitory

mechanisms

paroxysmal discharges

in the trigeminal

nucleus

attacks of trigeminal neuralgia

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CROSS TALK

NORMAL NERVES

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15Normal Trigeminal Nerve

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16Vascular compression of V nerve

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17Vascular irritation of V Nerve

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18Definition and classification of TN

Defining Symptomatology Diagnostic ClassificationIdiopathic  

sharp, shooting, electrical shock–like, Episodic pain TN1

aching, throbbing, burning, >50% constant pain TN2

Trigeminal injury  

unintentional (facial trauma; oral op;ear, nose, & throat op; skull baseop; posterior fossa op; or stroke)

Trigeminal Neuropathic pain

intentional (neurectomy, gangliolysis, rhizotomy, nucleotomy, tractotomy,or other denervating procedure)

Trigeminal deafferentation pain

Associated w/ MS symptomatic TN

Resulting from an outbreak of facial Herpes zoster post herpetic TN

Somatoform pain disorder atypical facial pain*

* Evaluation needed with psychological testing prior to confirmation.  

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19Clinical Features

Female: Male =2:1 6th decade (22months – 94yrs) Family History – 5% Bilateral, Sequential – 5% Commoner on right side(White & Sweet),R-61%: L-35%: B/L–4% V2+V3–32% : V2–17% : V3-15% : V1+V2+V3-17% : V1 rare Trigger areas – triggering stimuli Clicking in the ear Auricular Pain Absent during sleep Relief with Carbamazepine in 70-90%(Tyler Kabara et al,2002) 4-May-16

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SignsCorneal reflex Sensory examination – 25% have abnormalities

( Lewi & Grant, 1938) Motor examination – Asymmetrical jaw motion Ipsilateral nasolabial fold hypesthesia (Jannetta) Other deficits – Symptomatic TGN

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23Trigeminal Neuralgia & Multiple Sclerosis

10-20% of patients with MS present with TGN 1-8% of MS have TGN (Selby, 1984) Younger age group – 30 yrs mean Bilateral pain commoner than in idiopathic

TGN MR imaging may pick up sclerotic plaque at

root entry zone 2% of all TGN 4-May-16

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Investigations

X-Ray skull – AP through orbit, lateral, Towne’s view

CT head MRI Brain Electrophysiological Tests

– Evoked Potential (Lunsford et al, 1985) - Nd: Yag Laser Pulses (Romaniello et al, 2003) 4-May-16

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Higher petrous apex – Gardner et al, 1956 – 3 times higher incidence

Tip of dens > 5mm above McGregor’s line (43% vs 23% in controls)

Basilar Impressions Dolichocephaly Paget’s disease Postmenopausal Osteoporosis

X-Rays in TGN

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MRI in TGN Indications – Young patients

- Bilateral pain

- Atypical Neuralgia

- Neurologic deficits

MRI with MRA – Patel et al, 2003 – 92 patients

- 90.5% sensitivity, 100% specificity

MR tomographic angiography – Fukuda et al, 2003 – 67% correlation

MRI with constructive interference in steady state - Yoshino et al, 2003 – 80% correlation

Functional MRI, PET Scan with Opioidergic Imaging

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274-M

ay-16

CB - MRA (TOF)

Right Trigeminal Nerve

Compressing vessel

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CAVERNOUS ICA ANEURYSM

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30Diagnosis

TN is often misunderstood as pathology of dental origin. Many patients may go untreated for long periods of time before a correct diagnosis is made.

TN remains a clinical diagnosis. MRI and MRA can be performed if there is suspicion of underlying

pathology.

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31Evolution of therapies for TGN

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32 Medical Therapy – Later Medicines

Anticonvulsants

Muscle relaxants Anti depressantsTopical agentsFirst generation:

Phenytoin Carbamazepine Valproate Baclofen Amitriptyline Nortriptyline

Second generation:GabapentinOxcarbazepineLamotrigineZonisamideTopiramateLevetiracetamVenlafaxineDuloxetinePregabalin

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33Carbamazepine • Blom, 1962• Mainstay drug Therapy• Controls pain initially in approximately 90% of cases (Liu J.K, Apfelbaum; 2004)• Started as low dose dose escalation; drug synergism• Oxcarbazepine better tolerated (Beydoun.A, 2002)•Side effects: Leucopenia

Hyponatremia Rashes Elevation of Liver enzymes Alterations of Lipid profile Osteomalacia

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34Medical Treatment of TN

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Pain assessment

(Barrow Neurological Institute score)

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37Surgical Therapy

Indications : - Failure of medical therapy

- Intolerable adverse effects of drugs Methods: - Percutaneous - Open surgery - Radiosurgery

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38Percutaneous Procedures• Chemoneurolysis – Glycerol Rhizotomy

• Stereotactic Radiofrequency Rhizotomy

• Balloon compression

• Peripheral Neurectomy

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Chemoneurolysis • Bartholow (1876) – Chloroform : Neuber (1883) – Osmic Acid

• Schloesser (1904) – Alcohol

• Wright (1907) – Osmic Acid gangliolysis

• Harris (1910) – Alcohol gangliolysis

• Hartel (1914) – Percutaneous extra oral foramen ovale method

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40Percutaneous Retrogasserian

Glycerol Rhizotomy• 1981 – Hakanson – Glycerol+Tantalum dust

• Principle effects of Glycerol - Neurolytic - Hyperosmolarity - Affects large diameter Axons - Esp. previously demyelinated axons - Affects the trigger mechanism - May down regulate central hyperexcibility

- Bengt Linderoth, Sten Hakanson

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41Indications of PRGR

The main indication for glycerol rhizolysis remains classic idiopathic TN.

In medically infirm patients Anticonvulsants or baclofen causing severe

intolerant side effects particularly to patients with paroxysmal facial pain associated with multiple sclerosis (MS).

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42Technique of PRGR • No intra-op patient co-operation required – GA

• Position – initially supine – completed in semisitting

• Hartel’s technique

• Cisternography to assess volume

• Average 0.25ml (0.2-0.5ml)

• 99.9% anhydrous glycerol + tantalum injection

• Placed in semisitting position for 2hrs after the procedure

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Hartel’s anatomic landmarks for access to the foramen of ovale. A.Surgeon marks three points on the patient’s face: •A point 3 cm anterior to the external auditory meatus along a line from the external auditory meatus to the tip of the nose , •A point beneath the medial aspect of the pupil on the lower eyelid, and •A point 2.5 cm lateral to the oral commissure . B.The target is the foramen ovale, at the intersection of a vertical line (in the sagittal plane) extending through the point beneath the pupil (1) and a horizontal line (in the axial plane) through the point anterior to the external auditory meatus (2).

44Technique of PRGR

• 22-gauge lumbar cannula is inserted from a point approximately 3 to 4 cm lateral to the corner of the mouth. •The trajectory is aimed at a point that lies, in the lateral view, approximately 0.5 cm anterior to the anterior margin of the mandibular joint, and in the anteroposterior view, toward the medial margin of the pupil with the eyeball in the neutral position. 4-May-16

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Cannula trajectory toward the superior-medial aspect of the foramen ovale. A. The surgeon’s index finger rests alongside the molars, against the lateral pterygoid, to guide the cannula toward the foramen ovale and prevent penetration of the oral mucosa. The cannula is aimed at the foramen ovale via Hartel’s landmarks.B. If direct penetration of the foramen is not achieved, the surgeon can sequentially walk down the infratemporal fossa (arrow) to the superomedial aspect of the foramenovale.

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Technique of PRGR

Consecutive axial CT scan images of a patient with intracisternal tantalum dust.

The anteroposterior distance from the anterior portion of the oval foramen to the anterior portion of the mandible is measured.

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47Complications of PRGR • Headache – 15%

• Nausea, vomiting – 8%

• Depressor response – 15%

• Aseptic meningitis – 0.6%

• Herpes simplex perioralis – 37%

• Sensory loss – 51%

• Dysesthesia – 2% Lunsford et al, 1997

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48Percutaneous Balloon Compression (PBC)

Principle: Destruction of large myelinated pre-ganglionic fibers by compression against petrous bone and dural edge.

•GA, pacemaker, slight neck extension, flouroscopy•Hartel’s technique•#4 Fogarty catheter 17 to 22 mm beyond foramen at the porus trigeminus•0.75 to 1cc of 180mg% iohexol under pressure of 1200-1500mm Hg•Tissue compression pressure – 650 – 950 mm Hg•Upto 1 minute or 1.5 min in recurrence•Proper inflation – Pear shape : depressor response

Technique of PBC

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49Percutaneous Radiofrequency Stereotactic

Rhizotomy (PSR):

•Failure of drug therapy or adverse effects

• Advanced physiologic age

• Poor medical condition

• Multiple Sclerosis

• Patient’s choice

Indications of PSR

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50Principle : Selective destruction of A-delta & C fibers at lower temperatures Technique of PSR

•Day care procedure under image guidance• Supine, Neutral position of head, short GA• Hartel’s technique • Proper positioning indicated by CSF flow• Electrode localisation• Lesioning at 60-70 degree Centigrade for 70 seconds• Sequential lesions of 90 seconds with 5 degree Centigrade after each lesion• Dense hypalgesia in desired area subjectively assessed.

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51Complications of PSR

Common:

Dysesthesia – 11%Anaesthesia dolorosa – 0.2% Absent corneal Reflex – 3% V1, V2, V3 pain – 10.3% Keratitis – 0.6% Diplopia – 0.5% Masseter weakness – 7%

Rare:

Intracerebral HemorrhageStrokeMeningitisBlindnessCarotico – Cavernous FistulaTemporal lobe abscessSeizures

Tew JM Jr, Taha JM – 1995

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Vascular Compression of the Nerve

Demyelination of Axons

Ephaptic Transmission

Impaired segmental inhibition

Central Nuclear hyper activity

TGN

Principle of MVD

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54Vascular Compression

Arterial –56-76%Superior Cerebellar –(75.5%) Anterior Inferior cerebellar – 0-21% Other Arterioles

Venous 33-50%Trigeminal Vein Petrosal Veins

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55SCA COMPRESSION

A.The right trigeminal nerve is compressed by a tortuous basilar artery and the left trigeminal nerve is compressed by the main trunk of the SCA.

B. SCA bifurcates into rostral and caudal trunks before reaching the trigeminal nerve. The nerve is compressed by the caudal trunk.

C. SCA bifurcates distally to the nerve. The nerve is compressed by the main trunk.

D. SCA bifurcates before reaching the nerve. The nerve is compressed by both the rostral and caudal trunks.

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E. the nerve is compressed by a large pontine artery. F. the nerve is compressed by an AICA that has a high origin and loops upward into the medial surface of the nerve. The SCA passes around the brainstem above the nerve.

.

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57 Venous Compression

Superior petrosal Vein that empty into the superior petrosal sinuses most commonly compress the Trigeminal nerve

Tributaries: Transverse pontine Vein (most frequent) Ponto trigeminal Vein Vein of cerbellopontine fissure and Middle cerebellar

peduncle

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A. Anterior view. The veins that commonly compress the trigeminal nerve are tributaries of the superior petrosal veinB. a transverse pontine vein compresses the lateral side of the nerve and joins the veins of the middle cerebellar peduncle and cerebellopontine fissure to empty into a superior petrosal vein.C. the medial side of the nerve is compressed by a tortuous transverse pontine vein. D, the lateral side of the nerve is compressed by the junction of the transverse pontine vein withthe veins of the middle cerebellar peduncle and the cerebellopontine fissure

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59Procedure of MVD• Positioning – Mastoid topmost

• Retromastoid, suboccipital craniectomy – Dura opened

• Cerebellum retracted – arachnoid dissected

• Tackle petrosal veins, visualise the entire nerve

• Identify the offending vessel

• Teflon felt placement

• Wound closure

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Procedure of MVD

For decompression of the fifth cranial nerve, the incision (dotted line) is positioned as shown so that two thirds of the length is above the level of the mastoid notch. 4-May-16

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A. Schematic view of a left trigeminal nerve decompression.•The superior cerebellar artery is compressing the superior edge of thetrigeminal nerve. B. Elevation of the superior cerebellar artery reveals indentation and grooving by the artery.C. Shredded Teflon felt is gently worked in between the nerve and the compressing artery. D. The shredded Teflon felt is placed between the artery and the nerve so that the thrust of the arterial force is now directed away from the underlying nerve. 4-May-16

62Complications Positioning palsy

Intracerebellar Hematoma & edema

Hearing loss

Postop numbness, headache

Hemorrhage

CSF Leak

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63Results of MVD• Average success rate 78%, >90% when vessels found

• Avg recurrence rate 20-25%

• Max recurrence within 2yrs

• Major complications around 4% - cranial nerve deficits

• Mortality – 0.5%

• Numbness – 3-29%

• Hearing Loss < 4%

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64Prognostic Factors in MVD

Female gender

Duration of symptoms > 8yrs

Venous compression only

Lack of immediate post-op pain relief

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Gamma Knife Radiosurgery for TGN

• 1951 – Lars Leksell introduced

• Principle – Radiation induced damage to REZ after a latent period - Minimising damage to surrounding structures.

•Indications: Failed medical therapy Poor medical condition Recurrent TGN Patient’s choice

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66Gamma Knife

Single high dose radiotherapy delivered with exquisite precision to a radiographically defined target, at the junction of trigeminal nerve and brain stem.

Success rate is 70%

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67Technique of GKRS:

• Accurate imaging of the REZ with 1mm MRI slices

• 4mm isocenter targeted to REZ 2-4mm anterior to brain stem

• Brain stem receives < 20% isodose

• Length of nerve irradiated at 50% isodose is 4mm

• Total radiation dose of 70-90 Gy over 30mins

• Latent period for pain relief – upto 10 weeks

Robert W. Rand, 1997

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68Cyberknife Radiosurgery• Developed in 1994 – Accuracy, Inc., Sunnyvale, CA - Adler 1999, Chang 2001

• Non invassive head immobilisation & advanced image - guidance

• Dynamic tracking of skull – ensures target accuracy of 1.1mm

• Frameless procedure

• Delivers non isocentric, conformal, homogenous radiation to non spherical structures.

• Romanelli et al, 2003 – 10 patients with Trigeminal Neuralgia – 70% response.

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69Technique

• Single session – Medium maximum dose 78 Gy, median, marginal dose 65.5 Gy

• Median Target volume = 0.085 cm3

• Length of nerve encompassed by 79% isodose line = 7.2mm

• Target volume placed 2-3 mm anterior to REZ

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70Results:

• 92.7% successful pain relief at 7 days

• Pain relief – Excellent – 87.8 % Moderate – 4.9% No change – 7.3% • Long Term response rate 78%

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71Complications

• 73.2% had facial numbers at follow-up

• Anesthesia dolorosa – 5% • Depressed corneal reflex – 7.3%

• Masseter Weakness – 2.4%

• Trismus

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74Choice of surgical treatment

Relatively young patients with no co-morbidities: MVD Patients unable to tolerate GA:

Percutaneous procedures Stereotactic radiosurgery

Multiple sclerosis: SRS/ Percutaneous techniques/MVD Final choice based on patient’s preference and ability to

tolerate GA

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75Trigeminal Neuralgia: Opportunities for Research

Treatment of trigeminal neuralgia is like playing the game of dart, so far .

• Treatment is empirical, but not satisfactory 4-May-16

76Individuals of note with TN include

Entrepreneur and author Melissa Seymour (Australia) was diagnosed with TN in 2009 and underwent microvascular decompression.

Salman Khan , was diagnosed with TN in 2011 He underwent surgery in the US.

All-Ireland winning Gaelic footballer Christy Toye was diagnosed with the condition in 2013.

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