Y P O C T Neurological Applications of O N Transcranial - PowerPoint PPT Presentation

Y P O C T Neurological Applications of O N Transcranial Magnetic Stimulation O D Mouhsin Shafi, MD/PhD E Berenson-Allen Center for Noninvasive S Brain Stimulation A E BIDMC, Harvard Medical School L P

Y Overview of Talk P O C • FDA-Approved Indications T – Presurgical Motor & Language Mapping O – Migraine N • Diagnosis / Prognosis O D – Motor outcome after stroke, Epilepsy, Vegetative state E S • Therapeutics A – Review of results across neurologic indications E L P

Y P Motor / Language Mapping O C T • FDA approval of Nexstim O NBS device for: N – Mapping of the primary O motor cortex D – Localization of cortical areas E that do NOT contain S essential speech function A – For pre-procedural planning E L P Picht 2011 Neurosurgery

Y P Motor Cortical Output Mapping O C T O N O D E S A E L P Nagib et al. Neurosurg Clin 2011

Y P Motor Cortical Output Mapping O Comparing Noninvasive and Invasive Mapping C T O N O D E S A E L P Najib et al. Neurosurg Clin 2011

Y Motor mapping P O • Comparing nTMS to Direct Cortical Stimulation (DCS): C – Mean distance between nTMS T & DCS hotspots was 7.83 +/- 1.18 mm for APB (95% CI 5.36 O to 10.36 cm) N – nTMS and DCS hotspots were in same gyrus for all patients O D E S A E L P Picht 2011 Neurosurgery

Y nTMS vs fMRI P O • Several studies have evaluated accuracy of motor C mapping with nTMS vs fMRI (with DCS as gold standard) T – Forster 2011, Neurosurgery : 10 pts, mean distance to DCS O hotspot 10.5 +/- 5. 7 mm for nTMS vs 15.0 +/- 7.6 mm for fMRI N – Mangraviti 2013, Neurol Sci : 7 patients, mean distance to DCS O hotspot 8.5 +/- 4.6 mm for nTMS vs 12.9 +/- 5.7 mm for fMRI D Coburger 2013, Neurosurg Rev : 30 E patients; all 30 completed nTMS, S whereas only 23 completed fMRI. A Authors binned results into 4 E levels, where 1 is most accurate, 4 L P is least accurate

Y Motor mapping w/ nTMS improves outcome? P O • Krieg 2014 Neurosurgery : Compared outcomes in 100 C consecutive patients bw 2010-2013 vs 100 historical T controls without nTMS from immediately prior period O – All patients underwent intraoperative MEP monitoring as well N – Craniotomy size significantly smaller in nTMS group O – 12 pts in nTMS group improved, vs only 1 in control group D – Residual tumor in 22% of nTMS group vs 42% of controls E S A E L P

Y Motor mapping w/ nTMS improves outcome? P O • Frey 2014 Neurosurgery : Compared outcomes in 250 C consecutive pts from 2007 – 2012 with 115 controls T from 2005-2007 O – 165 cases with intraoperative stimulation mapping, nTMS N location of primary motor cortex confirmed in all cases. O – In 82 cases with navigated intraop stim, mean distance bw D nTMS and DCS hotspot was 6.2 mm (range 0.4 – 14.8 mm) E – Gross total resection achieved in 59% of nTMS group vs only S 42% of historical control, with no change in post-op deficits A Progression-free survival E significantly higher in nTMS L group than in control group P (15.5 vs 12.4 months), although no change in overall survival

Y Language mapping P O • Picht 2013, Neurosurgery : Evaluated nTMS and DCS C responses during language mapping in 20 patients with T tumors close to left-sided language areas O N O D E S A E L P

Y Language mapping … P O C T • A subsequent study O (Tarapore 2013, N NeuroImage ) also O demonstrated high D negative predictive value, with E improved specificity S A E L P

Y Compared with fMRI and DCS P O C Ille 2015a, b: T Compared language O mapping results from N rTMS (C) and fMRI (D) O with those from DCS D (B) E S A E L P

Y And may have beneficial effects P O C T O N O D E S A E L P Early language deficits decreased Craniotomy size smaller w/ TMS Sollman 2015

Y Abortive therapy migraine P O • FDA approval for the SpringTMS single-pulse C portable TMS system obtained for abortive therapy T of migraine with aura O N – 2 pulses of TMS administered approximately 30s apart to occipital region O D E S A E L P Image from www.medgadget.com

Y Efficacy in acute migraine P O • Randomized 201 patients with migraine with aura, 1-8 C episodes per month, aura for at least 30% of episodes T – 201 randomized, 164 had migraines and treated O N • Higher pain-free response rates after 2 hours (39% in verum vs 22% in sham), sustained at 24 and 48 hours O D HOWEVER, a number of secondary endpoints (patients E who achieved no or mild pain 2h S after treatment, use of rescue A drugs, consistency of pain relief, E global assessment of relief) L P showed no significant differences Lipton, Lancet Neurology 2010

MEPs predict functional recovery after Y P acute stroke O C T O N O D E S A E L P Stinear 2012, Brain

Paired-pulse measures identify cortical Y P hyperexcitability in Epilepsy O C T O N O D E S A Paired-pulse measures suggest altered excitation E / inhibition balance in patients with newly- L P diagnosed epilepsy compared to healthy controls Badawy 2007 Ann Neurol

Y And predict response to medications P O TMS-EMG paired-pulse C measures normalize in T patients who respond to O meds; no such changes seen N those with ongoing seizures O D E S A E L P Epilepsy patients, before meds Badawy 2010, Ann Neurol Epilepsy patients, after meds Normal controls

Y Diagnosis of Persistent Vegetative vs P Minimally Conscious State O Casali 2013, Science Trans Med C T O N O D E S A E L P Decreased complexity of evoked response in subjects with loss of consciousness due to any etiology, and in patients with vegetative versus minimally conscious versus locked-in states M /F

Y Theraputic effects? P O • rTMS has been studied as a therapeutic modality in C different neurologic conditions including T – Epilepsy O – Migraine prevention N – Motor rehabilitation after stroke O – Cognitive rehabilitation in post-stroke aphasia, post- stroke neglect and Alzheimer’s Disease D – Movement Disorders (primarily Parkinson’s) E – Chronic Pain S – Tinnitus A • However, FDA indication has not been yet obtained E for any of these (multi-center trials currently L underway in several disease conditions) P

Y Key References P O • Handbook of Clinical Neurology C – Volume 116, Pages 2-763, 2013; Edited by Andres T O Lozano and Mark Hallett N – Overview of Deep Brain Stimulation and Noninvasive O Brain Stimulation across spectrum of neurologic D diseases E • Lefaucheur et al, Clinical Neurophysiology 2014 S – Recent evidence-based review/guidelines on A therapeutic use of rTMS in neurologic and psychiatric E L diseases P

Y Principles for successful intervention P with TMS/tDCS O C • Known brain region or network T O • Known goal to enhance or decrease activity of N that network O • Target can be engaged by stimulation D intervention E S A E L P

Y Blinding in TMS studies is difficult P O • TMS produces C – An auditory clicking sound w/ bone conduction T – A tapping sensation (trigeminal afferents) O N – Contraction of the temporalis and frontalis muscles • Particularly problematic in trials in which “real” O D stimulation is used to determine motor threshold for titration of stimulation intensity  crossover trials E S compromised, parallel-group studies are needed! A • Recently, placebo coils that can be preprogrammed E and that use electrical stimulation to produce scalp L P sensations have become commercially available

Y As a result study quality is often poor P O C T O N O D E S A E • Primarily due to lack of allocation concealment and inadequate blinding of participants (e.g. coil tilted away as sham stimulation group). Random sequence L generation also often not specified in reports P Shafi et al, in preparation

Y An overview of the current evidence P O C T O N O D E S A E L P Shafi et al, in preparation

Y TMS and tDCS for Neurological indications P O C T O N O D E S A E L P

Y Epilepsy P O • Trials have assessed the utility of rTMS in C medication-refractory epilepsy (~1/3 of patients) T O – Typically apply low-frequency rTMS to the epileptic N focus or have applied to the vertex (regardless of O location of epileptic focus) D E S A E L P Lefaucheur 2014 Clin Neurophys