NEUROMODULATION in Psychiatric Disorders
Giovanni Broggi,
Dept of NeurosurgeryFond. Istituto Neurologico C.Besta
Milano Italy
A LONG SHADOW OVER THE SOUL- Fano –March 29-31,2012
NEUROMODULATION in Psychiatric Disorders
• Deep Brain Stimulation –DBS
Different targets
• Vagal Nerve Stimulation-- VNS
Indications:•OCD•DISRUPTIVE BEHAVIOUR•SOMATOFORM DISORDERS•MAYOR DEPRESSION•Gilles de la TOURETTE
NEUROMODULATION in Psychiatric Disorders
DBS
VNSIndication:MAYOR DEPRESSION
Neurosurgery for Psychiatric Diseases in Italy
Giovanni BroggiDept of Neurosurgery
Fond. Istituto Neurologico C.BestaMilano, Italy
World Federation Societies Stereo-Functional NeurosurgeryINTERNATIONAL FORUM OF PSYCHIATRIC SURGERY
SHANGHAI, MARCH 9-11, 2011
WHAT IS THE STATE OF ART of Surgery for Psychiatric Disorders the World?
DBS • Milano Besta
– 7 cases for aggressive behavior (post Hyp)– 5 cases of OCD ( ACC)– 1 case somatoform disease, pain ( B.A.24)– 3 cases of major depression ( B.A. 25)– 5 case of Gilles Tourette ( GPi // cortex B.A.9-46)
• Milano Galeazzi– 32 case of Gilles Tourette (Vop-CM // Gpi)
VNS for Major Depression
Milano Besta 21 cases
Torino Univ 11 cases
Udine Hospital 6 cases 2011
Neurosurgery for Psychiatric Diseases
Mood & Mind SupplementumWorld Neurosurgery 2012
•Surgery for Psychiatric DisoedersD.A.J.P.Denys- Amsterdam
•Surgery in Tourette SyndroemVaerle Visser-Vandevalle-Maastricht
•DBS for OCDStephane Chabardes- Grenoble
•DBS for Alcool dependencyJ.Voges- Maagdeburg
WSSFN ad hoc Committe for Ethical Guidlines
DELGADO, M. R., H. HAMLIN and W. P. CHAPMAN. Technique of intracranial electrode implacement for recording and stimulation and its possible therapeutic value in psychotic patients. Conf. neurol., 12:315-319, 1952.
INCB Criteria of Patiens selection
• Diagnosis by the referral psychiatrist• Control and agreement on the diagnosis
by two indipendent psychiatrist
• Neuroradiological studies
• Team ( psychiatrist, neurologist, neurosurgeons) discussion and agreement
• Informed consensus to surgery ( patient , family or legal tutor)
Deep brain stimulation of the accumbens nucleusIn treatment of obsessive compulsive diseases.
Preliminary experiences
Coordinates of Nucleus Accumbens:
2.5 mm rostral anterior border of
AC (Z)
6.5 mm lateral of midline (X)
- 4.5 mm ventral AC (Y)
Dedicated computational software for detecting Anterior Nucleocapsular regionDedicated computational software for detecting Anterior Nucleocapsular region
No discharge specific pattern in NAWith thw exception of few neurons with discharge frequency of 15Hz But with some episode of ~200Hz (doublets) frquency
Microrecording on Nucleus Accumbens
70-200ms
Time (s) 1 s
μV
1
Time (s)S
pike
s\s
Microrecording on Nucleus Accumbens
STABLE AT 4 years
Follow-up
Follow up In Patient 2: Decrease of YBOCS score from 30 to 12Decrease of YBOCS score from 30 to 12
Increase of GAF score from 41 to 60Increase of GAF score from 41 to 60
?
BOTH PATIENTS REFRACTORY TO CONSERVATIVE TREATMENTBOTH PATIENTS SELECTED BY TWO INDEPENDENT PSYCHIATRIC TEAMS
BOTH PATIENTS OBTAINED SIGNIFICANT IMPROVEMENT BY DBS
BOTH PATIENTS REGAINED SOCIAL LIFE(work , friends , hobbies…)
~~~~~~~~~~~
ONE PATIENTS IS REALLY SATISFIED(“I have been cured”)
ONE PATIENTS IS NOT SATISFIED(“still I feel me unhappy , sick..”)
Results on QoL
ANGELO FRANZINI GIUSEPPE MESSINA CARLO MARRAS GIOVANNI TRINGALI GIOVANNI BROGGI
Hypothalamic neuromodulationfor aggressive behaviour
The ProblemRage attacks , self aggression , and disruptive
behaviour
resistent to conservative treatments
in mentally retarded patients
---------
connatal idiopathic
brain damage ( trauma , encephalitis)
----------
Frequent comorbidity for epilepsy
Lesioning of the same target K. Sano. 1970
The Sano graphic reconstruction of electrodes tracks and the fusion between RM and postoperative CT with electrodes implanted
within the posterior hypothalamus
Sano K. 1970
May A. 1999
Franzini et al. 2003
STEREOTACTIC COORDINATES TO THE AC-PC MIDPOINT:
X = +/- 2 (ventricular wall)Y = -3 (correction needed)Z = -5
DEACTIVATION during pHyp DBS
STEREOTACTIC COORDINATES AND TECHNICAL PROBLEMS
STIMULATION PARAMETERS 180 Hz 90 usec1-2.5 Volt
INTRAOPERATIVE EVOKED
RESPONSE
• -Vertigo, ocular movement disturbances(>3V.)
• -Sense of fear(>4V.)
– Bipolar stimulation at the target
100 ms
The frequency of single unit action potentials is about 15-16 Hz
Posterior Hypothalamus microrecording
No specific neuronal discharge pattern
THE FIRST CASE Clinical Case : 34 yrs old maleMental retardation : iQ < 40
Refractory epilepsyINTRACTABLE DISRUPTIVE BEHAVIOUR isolation (4 years)
Neuroleptics drowsisness – epilepsy – tardive dystonia
Withdrawald of neuroleptics Two weeks after surgery
Recover of social activities two months after surgery
Decrease of seizures rate 50% (neuroleptics ?)
no more isolation
four years follow-up
Normalnomultifocal3020Idiopathic6 C.C.
Bilateral temporal porencephaly
nonoNot evaluable37Post-traumatic5 D.C.
Bilateral frontal cortical atrophy
InsomniaSevere arterial hypertension
no3064Post-anoxia4 C.A.
Normalnono4021Idiopathic3 P.M.
NormalnonoNot evaluable34Perinatal Toxoplasmosis
2 B.A.
NormalnomultifocalNot evaluable26Idiopathic1 P.G.
neuroimaging epilepsy IQage aetiology patients
2004 – 2008 6 patients
Posteromedial hypothalamic stimulation for aggressive and disruptive behaviour in IQ subaverage patients
RESPONDERS
NON RESPONDERS
LONG TERM RESPONDERS (67%)
-Neuroleptics dosage decrease > 50%-No more Hospitalization-No more contentive measures-Family or therapeutic community stay-Improvement of cognitive functions-Marked reduction of epileptic seizures (2 epileptics)
-Adverse effects--Slight worsening of neck dystonia (2 patients) when stimulating with the most caudal contact--Impairement of ocular movements when the current amplitude > 3 Volts
DISAPPEARANCE OF SELF-AGGRESSIVE BEHAVIOR IN A BRAIN-INJURED PATIENT AFTER DEEP BRAIN STIMULATION OF THE HYPOTHALAMUS:TECHNICAL CASE REPORT.
Neurosurgery. 62(5):E1182, May 2008.
Kuhn, Jens M.D.; Lenartz, Doris M.D.; Mai, Jurgen K. M.D.; Huff, Wolfgang M.D.; Klosterkoetter, Joachim M.D.; Sturm, Volker M.D
40 pts
Somatoform Disorders Common Characteristics
Disorders in this category include those where the symptoms suggest
a medical condition but where no medical condition can be found by a physician.
In other words, a person with a somatoform disorder might experience significant pain without
a medical or biological cause, or they may constantly experience minor aches
and pains without any reason for these pains to exist.
Somatoform Disorders
PrognosisPoor. The course is typically chronic and persists for years, and often involves other symptoms such as depression, anxiety, and drug abuse.
Radiosurgycal cyngulotomy for chronic pain
Nature Neuroscience 2, 403 - 405 (1999) doi:10.1038/8065
Pain-related neurons in the human cingulate cortexW. D. Hutchison1, K. D. Davis, A. M. Lozano
R. R. Tasker1 & J. O. Dostrovsky
Stereotact Funct Neurosurg 1992;59:33-38
Deep Brain Stimulation of the Anterior Cingulate Cortex (ACC)Brodman area 24
ATYPICAL FACIAL PAIN
60 years female patient
More than 10 years of chronic pain of the face perioral area
Refractory to any kind of drugs treatment including opioids ,neuroleptics ,antiepileptics etc..
No social life , completely invalidated
After four months of high frequency stimulation of the Cingulate cortex (Brodman area 24) the patient became
pain free
At 3 year, follow-up still control of pain, that became episodic instaed of continous
Deep Brain Stimulation for Treatment-Resistant Depression
Neuron, Volume 45, Issue 5, Pages 651-660H.Mayberg, A.Lozano, V.Voon, H.McNeely, D.Seminowicz, C.Hamani, J.Schwalb, S.Kennedy
Case 1
2 years follow up
Case 2
Case 1 46 years old , male
Diagnosis of bipolar depression 22 years old (one maniac episode)
Psychoterapy
Drug therapy
ECT (6 times)
VNS (2 years)
HRDS 1 = 32
HRDS 1 = 5
Patients and relatives satisfied 18 months follow-up
www.angelofranzini.com
DBS for Psychiatric Disorders at Besta
Area 25 Area 24
N ACC
P Hyp
VNS For Depressive Disorder
Nucleus Tratctus Solitarus
AFFERENTSAFFERENTS
- Vagal nerve
- Carotid sinus nerve
- Aortic depressor nerve
- Cranial nerves V, VII e IX
- Grey substace of spinal cord (through the “spinosolitary tract”)
- Area postrema
- Rostro-ventro-lateral portion of medulla
- Parabrachialis nucleus
- Dorsal tegmental nucleus of mesencephalus
- Paraventricular nucleus of hypothalamus
- Posterior portions of lateral hypothalamic nuclei
- Central nucleus of amygdala
VNS For Depressive Disorder
VNS SURGERY
VNS:VNS:
Modification of regional functional anatomy Modification of regional functional anatomy
Main conceptual benchmarks in the genesis of depression:
- imbalance in the prefrontal-limbic circuit
-VNS could modify such balance
Functional Magnetic Resonance (fMRI) may evidence the immediate effects of VNS
SPECT and PET may evidence long-term effects
VNS VNS modification of regional functional anatomymodification of regional functional anatomy
fMRI fMRI (Chae et al. , 2002)(Chae et al. , 2002)
•At VNS immediate activationAt VNS immediate activation
• Prefrontal gyri, Caudate nuclei, Prefrontal gyri, Caudate nuclei, • temporal and parietal lobes, temporal and parietal lobes,
CerebellumCerebellum
•After 2 weeks of VNS : After 2 weeks of VNS : Frontal and Temporal LobesFrontal and Temporal Lobes
OccipitalOccipital Lobe and Cerebellum Lobe and Cerebellum
Blood flow increases: yellow
Blood flow decreases: blue
Acute VNS study with PET images superimposed on MRI images:
1: High frequency stimulation group
2: Low frequency stimulation group
1
2
(Henry T, 2002)
PET STUDIES
74 European patients with therapy-resistant major depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS.
Journal of Clinical Psychopharmacology & Volume 30, Number 3, June 2010
Mixed-model repeated-measures analysis of variance revealed a significant reduction (P ≤ 0.05) at all the 3 time points in the 28-item Hamilton Rating Scale for Depression (HRSD28) score
•53.1% (26/49) of the patients fulfilled the response criteria (Q50% reduction in the HRSD28 scores from baseline)
• 38.9% (19/49) fulfilled the remission criteria(HRSD28 scores e 10).
From January 2004 to November 2006 fourteen patients with TRD From January 2004 to November 2006 fourteen patients with TRD (age 43 to 80; ten men and four women) underwent VNS(age 43 to 80; ten men and four women) underwent VNS
• Baseline scores: ≥ 20≥ 20 on HDRS21.
• All of them had failed at least four antidepressant trialsfour antidepressant trials in their current major depressive episode
3. They did not benefit from a minimum of 6 months6 months of psychotherapy and their current episode was lasting for at least two years.at least two years.
0
10
20
30
40
50
60
Impl
ant
1 m
th
4 m
th
8 m
th
12 m
th2
yrs
4 yr
s6
yrs
7 yr
s
Time
HR
SD
Pat 1Pat 2Pat 3Pat 4Pat 5Pat 6Pat 7Pat 8Pat 9Pat 10Pat 11Pat 12Pat 13Pat 14
Diagram of ongoing of HDRS21 score in 14 patients with a follow-up of at least 1 year, as a function of time.
Arrow indicates the clinical worsening of patient 2 which occurred after IPG’s Battery Depletion
Responders ( HRSDResponders ( HRSD21 21 < 50 %) : 71%< 50 %) : 71%
Results:Results::HRSD 21 score ≤ 50 % of baseline score (responsiveness)
HRSD 21 score < 10 as absolute value (remittance)
4 patients4 patients did not responde to either criteria
10 Patients10 Patients responded to the responsiveness criterion
(HRSD 21 score ≤ 50 % of baseline score )
7 out of these 10 patients7 out of these 10 patients also met the criterion for remittanceremittance
(HRSD 21 score < 10 as absolute value)
VNS For Depressive Disorder
acknowledgement
• Angelo Franzini
• Giuseppe Messina
• Giovanni Tringali• Morgan Broggi
• Orsola Gambini
• Carlo Marras
• Vittoria Nazzi
THANKS FOR THE ATTENTION
Thanks for attention
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