Transcranial Magnetic Stimulation (TMS) in Clinical and ...

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  • Transcranial Magnetic Stimulation (TMS) in Clinical and Experimental

    Epilepsy

    Alexander Rotenberg, M.D., Ph.D. Dept. Neurology

    Childrens 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    Lesional and contra-lesional mapping (Rotenberg, unpublished)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

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