Transcranial Magnetic Stimulation (TMS) in Clinical and Experimental
Epilepsy
Alexander Rotenberg, M.D., Ph.D. Dept. Neurology
Children’s Hospital, Boston
Nexstim Inc.
TMS Basics
Frye, Rotenberg et al., 2007
• Focal, noninvasive cortical stimulation • Two FDA-approved devices:
• presurgical motor mapping • treatment of major depression
Neuronetics Inc.
TMS in Presurgical* Motor ** Mapping Motor
Perilesional mapping (Najib et al., 2011)
Lesional and contra-lesional mapping (Rotenberg, unpublished)
*Particularly for patients who do not tolerate Wada or fMRI **TMS for language mapping: likely soon
R hand L hand
Antiepileptic rTMS
- Numerous open label trials; three RCT - Most effective if over superficial neocortical focus - 1 Hz rTMS more effective than other low frequencies
Theodore et al., 2003 (11)
Cantello et al., 2007 (43)
Fregni et al., 2006 (9)
Theodore et al., 2003 (6)
Cantello et al., 2007 (43)
Fregni et al., 2006 (3)
Theodore et al., 2003 (6)
Fregni et al., 2006 (9)
Change in Seizure Frequency (%) a4er 0.3-‐1 Hz rTMS
Target rTMS
Placebo rTMS
2.0 -‐71.6 --6.0
(modified from Bae et al., Epilepsy Behav 2011)
Nontarget rTMS
Deep TMS H-Coil System
Epilepsy Therapy Project Award: Controlled trial of 1 Hz rTMS for treatment of temporal lobe epilepsy
1
Conditioning TMS
2 Test TMS
Control
SICI; 2 ms ISI
ICF; 12 ms ISI 0.5 mV
25 ms
LICI; 200 ms ISI
0.5 mV
50 ms Rotenberg and Pascual-Leone, 2010
Measures of Cortical Excitability by Paired-Pulse TMS (ppTMS)
ISI
Brodtmann et al., Neurology 1999
TMS Biomarkers in Epilepsy
Loss of inhibition in epilepsy
Di Lazzarro et al., Neurology 2004
Enhanced inhibition with VNS
Drug Mode MT MEP SICI ICF
CBZ Na+ + = - -
LTG Na+ +++ - = =
PHT Na+ ++ - = =
LZP GABA = - ++ -
DZP GABA = - + -
TMS and drugs
Zieman, Clin Neurophys 2004
Cantello et al., Epilepsia 2007;
Enhanced inhibition in keto diet
Future directions: THANKS!
CHB – Frances Jensen – Blaise Bourgeois – Ann Marie Bergin – Tobias Loddenkemper – Masanori Takeoka – Andrew Vahabzadeh – Tsung-Hsun Hsien – Sameer Dhame – Paul Muller – Mustafa Hameed – Grant Goodrich – Lindsay Oberman – Roman Gersner – Guangpin Zhang
BIDMC / Spaulding – Alvaro Pascual-Leone – Donald Schomer – Felipe Fregni – Steve Schachter
SUPPORT – Epilepsy Research
Foundation – CIMIT – CURE – Department of Defense – NIH NINDS – Siegal and al Rashedi
families – Brainsway Inc. – Nexstim Inc.
Translational TMS: Measures of cortical inhibition in post-traumatic epileptogenesis
Normal rat
TBI rat
LICI
Weeks after TBIPre 1WK 2WKS 3WKS 4WKS 5WKS 6WKS
Rat
io
0.0
0.2
0.4
0.6
0.8
1.0Sham control ratsTBI rats
*** *
*
Hsieh et al., 2011
ppTMS in ketogenic diet: Does increase in cortical inhibition predict diet success?
rTMS in status epilepticus: Can rTMS suppress ongoing focal seizures?
TMS for preoperative language and motor mapping: Can rTMS supplement (or replace) Wada for some patients?
Language mapping
