Hilik Levkovitz MD,MHA

Professor

Director Day Hospital & Cognitive and Emotional

Lab.

School of Medicine, Tel Aviv University,

Israel.

Deep Transcranial Magnetic Stimulation (TMS) for Tourette

Syndrom

Dr. Levkovitz is a consultant and get a

regular consultant fee from Brainsway Ltd.

Disclosure

Previous rTMS Studies in Tourette Syndrome

• 12 subjects, 1Hz, 80% of MT, 3 gorupd : left premotor, left motor, left sham. No

improvement (Munchau et al. 2002, Orth et al. 2004)

• 8 subjects, 1 or 15 Hz, 110% of MT, 3 groups: left premotor, left motor, left sham.

6 days. Improvement in OC but not tic symptoms (Jeong-Ho et al. 2004)

• 5 subjects, 1 Hz, 100% of MT, SMA, 14 days. Significant improvement in Tics

(Mantovani et al. 2006)

Barker, 1984Barker, 1984

Magstim Rapid Stimulator

Cooling System CS03

Head Support

Helmet comprising the H1/H2 Coil

First Generation Second Generation

First Generation TMS Device is Limited in Contribution to the Treatment of

Neuropsychiatry Disorder

Multicenter studies, O’Reardon, 2007, George, 2010

Example: Superficial TMS Limited in Direct Stimulated of Deep Brain Regions

Superficial TMS is limited to superficial cortex (1-1.5 cm stimulation depth)

Emotion-regulating brain circuitis located deep within the brain

H1L Coil (120% MT)H1 Coil (120% MT)

E [V/m]

H2 Coil (120% MT)

RED AND RED AND ORANGE ORANGE COLORS COLORS

REPRESENT REPRESENT BRAIN BRAIN

ACTIVATIONACTIVATION

Phantom Brain MeasurementsElectric field distribution

of the H coils and figure of 8 at 120% MT

Figure of 8 Coil (120% MT)

While figure of 8 stimulate 1-1.5 cm the H coils reach to 5-

6 cm beneath the cortex

Roth et al. J. Clin. Neurophysiology 2007

Acute feasibility and safety study in Depression

LR LR LR LR

Left BilateralPartial Left Standard coil

H1 deep TMS (1Hz) disrupts mPFC functional connectivity during rest

b

P<0.001Sham TMS subjects

Figure-8 subjectsDeep TMS subjects X=-5

PF

aDeep TMS subjects

Figure-8 subjectsSham TMS subjects

X=-9

Front Hum Neuroscience. 2011

• Deeper penetration leads to activate brain circuit located deep within the brain• Different coils target to different brain area

H-coil Transcranial Magnetic Stimulation (TMS)

Overview of Clinical Trials in Overview of Clinical Trials in DepressionDepression

Safety in normal volunteers (n=35 )

Clin Neurophysiol. 2007

Acute feasibility and safety study in MDD (n=63) Brain Stimul. 2009

Long-term feasibility and safety study

in MDD (n=30) World J Biol Psychiatry 2012

Randomized, controlled, multi-centre study

(efficacy) (n=230)

21 sites (15 from North America , 2 from Europe and 4 from Israel) participate in the study and this was one of

the biggest studies in the field of TMS.

International sites include:

Primary end point: Change in depression

Change in depression & history of failed on antidepressant

medications

Subjects who failed >2 medications in the current episode, showed a significant improve on deep TMS treatment relative to sham.

Prospective, Multicenter, Double-Blind, Randomized, Sham Controlled Trial

•12 TS patients•Y-GTSS > 20 at screening.• Did not response to at least 2 full trials of anti-

tic pharmacotherapy

•Trial duration 4 weeks•1 Hz, 110% of the measured MT, total of 1200

pulses per session

•Change from baseline in YGTSS at week 4

• Change from baseline in YBOX at week 4•Change from baseline in QIDS at week 4•Change from baseline in CGI at week 4

PatientsPatients

TreatmenTreatmentt

Primary Endpoint

SecondarSecondary y

EndpointEndpointss

Feasibility Study in Tourette Syndrome

Yale-Brown Obsessive Compulsive Disorder Scale

(YBOCS)

Yale Global Tic Severity rating Scale (YGTSS)

Clinical Global Impression (CGI)

Social Adaptation Self-evaluation Scale (SASS)

Hamilton Anxiety Rating Scale (HARS-14)

Level of depression (HDRS-21)

Subjective improvement (IDS-SR)

Efficacy rating scales used in the study

Primary end-point: Change in tics at the end of week 4

Secondary end-point: Change in Obsessive-Compulsive symptoms at

the end of week 4

Primary end-point: change in tics at the end of week 4

For sub-group of patients suffered from Tourette & OCD :

Tics improved significantly (p=0.047) OC symptoms a trend for

improvement on YBOCS (p= 0.065)

Thanks !Thanks !