Intraoperative Monitoring: Role in Epilepsy Based Tumor Surgery December 2, 2012

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1 Intraoperative Monitoring: Role in Epilepsy Based Tumor Surgery December 2, 2012 Aatif M. Husain, M.D. Duke University and Veterans Affairs Medical Centers, Durham, NC American Epilepsy Society Annual Meeting

2 Disclosures Name of Commercial Interest UCB Pharma Upsher Smith Laboratories Jazz Pharma Demos Medical Publishing Type of Financial Relationship Research, consultation, speaker bureau Research, consultation Consultation, speaker bureau Royalties American Epilepsy Society Annual Meeting 2012

3 Learning Objectives Understand technique and utility of language mapping Understand techniques used for motor cortex localization Compare various techniques used for motor mapping and monitoring American Epilepsy Society Annual Meeting 2012

4 Overview Language mapping and monitoring Central sulcus/motor cortex localization Motor pathway monitoring Intraoperative ECoG

5 Language Mapping Rationale Localization of language areas very variable Resection in eloquent area may be possible Identifies clinical function of neural tissue Cautions Mapping may result in seizures After discharges must be monitored Awake patient

6 Language Mapping Technique Cortical areas stimulated with bipolar constantcurrent stimulator (Penfield technique) 60 Hz trains of biphasic pulses Each pulse 1 ms. (2-10 ma per pulse) Train duration 3 5 seconds ECoG obtained with strip electrode(s) After discharge threshold identified Mapping performed with stimulation intensity 2 ma less than AD threshold Naming task performed

7 Patient 1: 24 year old, right-handed woman started having CPS 6 months prior to referral to epilepsy center. Seizure have continued despite treatment with LEV and LCM.

8 Patient 1: After Discharge

Patient 1: 24 year old, right-handed woman started having CPS 6 months prior to referral to epilepsy center. Seizure have continued despite treatment with LEV and LCM.

9 Patient 1: 24 year old, right-handed woman started having CPS 6 months prior to referral to epilepsy center. Seizure have continued despite treatment with LEV and LCM. Broca s area (Tag 10) Tongue motor (Tag 1) Tongue sensory (Tag 2) Auditory naming (Tag 30) Superior Tumor (Tag 21) Posterior 1, 10 = PreCen Gyrus 2 = PostCen Gyrus 20, 22, 24, 26 = STG 21, 23, 25 = MTG 30 = Ant Supramarginal 1cm ruler at bottom right Slide courtesy Sandra Serafini, Ph.D.

10 Patient 1: 24 year old, right-handed woman started having CPS 6 months prior to referral to epilepsy center. Seizure have continued despite treatment with LEV and LCM. Superior Broca s area (Tag 10) Tongue motor (Tag 1) Tongue sensory (Tag 2) Auditory naming (Tag 30) Tumor (Tag 21) Posterior 1, 10 = PreCen Gyrus 2 = PostCen Gyrus 20, 22, 24, 26 = STG 21, 23, 25 = MTG 30 = Ant Supramarginal 1cm ruler at bottom right Slide courtesy Sandra Serafini, Ph.D.

11 ARS Question Should language mapping be performed in all cases of dominant hemisphere fronto-temporalparietal tumor/epilepsy surgery? A. Yes B. No C. No opinion

N=29 #raw sites=204 2V, 10VA, 17VAS #SpArr=29 1 0 0 0 2 0 11 3 7 1 7 10 10 3 2 3 1 2 2 17 16

12 N=29 #raw sites=204 2V, 10VA, 17VAS #SpArr= Visual Auditory Sentence Completion Speech Arrest

13 Language Monitoring Resection rule: resect > 1 cm. from essential site to avoid functional deficit Visual naming task Monitor language function during resection Testing during resection Testing with electrical stimulation 7 patients with LGG in Broca s area resection with language mapping and monitoring Stimulation during resection caused language deficits White matter between anterior insula and pars orbitalis (anterior margin) Fibers from ventral premotor cortex (posterior margin) Anterior part of arcuate fasciculus (depth) Head of caudate nucleus Postoperatively transient language worsening but no permanent deficits Haglund MM et al. Neurosurg, 1994;34: Benzagmout M et al. Neurosurg, 2007;61:

$refractory to medications; undergoing tumor resective$ surgery.

14 Patient 2: 15 year old male with ganglioglioma and epilepsy refractory to medications; undergoing tumor resective surgery. Pre-resection No errors in 6 stim trials Hesitations w/ resection Post-resection Slide courtesy Sandra Serafini, Ph.D.

15 Central Sulcus/Motor Cortex Localization Rationale Location of central sulcus not visually obvious, especially in cases of tumors Resection in eloquent area may be possible Identifies clinical function of neural tissue Cautions Mapping may result in seizures Injury to white matter fiber tracts can cause complications Techniques Median (? tibial) SEP Electrical stimulation (Penfield technique) Direct cortical stimulation

16 Median SEP N20 Phase Reversal Legatt AD, Kader A. J Clin Neurophysiol, 2000;17: Robertson SC et al. In: Intraoperative monitoring techniques in neurosurgery, 1994:

17 Median SEP Technique Stimulation of median nerve Recording from exposed cortex with strip/grid electrode Referential recording with distant reference Largest amplitude N20 over somatosensory cortex Anterior-posterior phase reversal marks central sulcus Electrode position must be moved to check for variations, especially when lesions present

$with medically refractory epilepsy undergoing surgery to resect left parietal$

18 Patient 2: 5 year old male with tuberous sclerosis and multiple cortical tubers with medically refractory epilepsy undergoing surgery to resect left parietal lesion.

$medically refractory epilepsy undergoing surgery$

19 Patient 2: 5 year old male with tuberous sclerosis and multiple cortical tubers with medically refractory epilepsy undergoing surgery to resect left parietal lesion. Superior Posterior Tuber 5 6

20 Electrical Stimulation Technique Cortical areas stimulated with bipolar constantcurrent stimulator (Penfield technique) ECoG obtained with strip electrode(s) After discharges monitored Observation of face/limbs EMG monitoring of face/limbs Clinical seizures common

EMG Recording EMG recording from face, limbs increased sensitivity of motor mapping 24% of patients had clinical or subclinical seizures during mapping

21 EMG Recording EMG recording from face, limbs increased sensitivity of motor mapping 24% of patients had clinical or subclinical seizures during mapping Mapping method less likely to produce seizures 3.6 ma 3.6 ma 5.0 ma 6.2 ma Stimulation at 60 Hz, 1 ms pulse Yingling CD et al. J Neurosurg. 1999;91:

22 ARS Question I use electrical stimulation (Penfield method) for motor cortex localization during tumor surgery for epilepsy. A. True B. False C. Uncertain

23 Direct Cortical Stimulation Technique Stimulation (anode) with strip electrode placed on cortex; same electrode used for median SEP Cathode placed distally Monopolar stimulator can be used Standard stimulator with 0.05 ms pulse width 5 pulse train, ms ISI Stimulation intensity up to 20 ma/60 V Some report intensities up to 25 ma/110 V* EMG recording electrodes in face, limbs *Cedzich C et al. Neurosurg, 1996;38:

24 Direct Cortical Stimulation Mapping Nonrecurrent pulse trains used Subdural strip placed perpendicular to central sulcus Various contacts on subdural strip sequentially stimulated Hand-held bipolar or monopolar stimulator can be used Site of lowest intensity stimulus evoking MEP response is over motor cortex Monitoring Strip electrode rotated to lie parallel to central sulcus Lowest stimulus intensity that evokes MEP used MEP recorded from restricted group of muscles Multiples sites may need to be stimulated to evoke hand/leg responses Hand and foot sites stimulated with monopolar or bipolar derivation Repeated throughout surgery Cedzich C et al. Neurosurg, 1996;38: Yingling CD. US Neurology, 2011;7:64-67.

25 Patient 2: 5 year old male with tuberous sclerosis and multiple cortical tubers with medically refractory epilepsy undergoing surgery to resect left parietal lesion. Superior R HAND R ARM R Delt-R Delt' RMG R ANT TIB R FOOT R OCULI 8 V Posterior 10 V

26 Electrical vs. Direct Cortical Stimulation Electrical Stimulation Incidence of seizures: 9.5% Movement with stimulation Activates cortical neurons Cannot be done continuously during surgery No/light anesthesia Higher total charge delivery FDA approved Direct Cortical Stimulation Incidence of seizures: 1.2% No movement with stimulation Activates cortical neurons To be used continuously during surgery General anesthesia Much lower charge density Not FDA approved (yet) Szelenyi A et al. J Clin Neurophysiol, 2007;24:39-43

27 Transcranial vs. Direct Cortical Transcranial Stimulation Stimulation Direct Cortical Stimulation 75 µs pw, 9 pulses, 2 ms ISI, 330 V 75 µs pw, 7 pulses, 2 ms ISI, 40 V tcemep can activate subcortical pathways Yingling CD. US Neurology, 2011;7:64-67.

28 Subcortical Mapping with Intraoperative Imaging 42 patients with corticospinal tract tractography coregistered to surgical navigation-derived images Direct subcortical stimulation with monopolar stimulator, ma intensity; recording from muscles Intraoperative ultrasound during stimulation; compared to tractography based neuronavigation Stimulation thresholds compared to distance to corticospinal tracts Nossek E et al. J Neurosurg, 2011;114:

29 Subcortical Mapping - Tractography Stimulation threshold increases approximately 1 ma/mm of distance from CST Subcortical MEP threshold of 3 ma is cutoff for new CST deficits Nossek E et al. J Neurosurg, 2011;114:

30 ARS Question Motor cortex mapping and monitoring reduces morbidity. A. True B. False C. Uncertain

31 Review of Motor Mapping/Monitoring Mapping 70 patients with brain tumors underwent motor mapping with SEP and motor cortex stimulation Localization of central sulcus with SEP in 100% DCS elicited MEP in 95.7% DCS stimulation intensity ma in precentral gyrus, ma in other areas No complications observed N=25 No changes (n=10) Temporary MEP loss (n=9) Permanent MEP loss (n=5+1) Monitoring No new deficit (%) Temporary new deficit (%) Permanent new deficit (%) 9 (90) 1 (10) 1 (12) 4 (44) 4 (44) (100) MEP amplitudes vary widely Lack of comparable series uncertain if monitoring reduces morbidity Kombos Th et al. Acta Neurochir, 2000;142: Cedzich C et al. Neurosurg, 1996;38:

32 Conclusions Distribution of language sites variable mapping important to avoid damage Motor cortex localization/mapping done with many different techniques New mapping techniques have advantages over older methods Motor monitoring during tumor dissection may prevent injury to CST

1/22/2015. Royalties from Demos Medical Publishing. Learn how to. Mirela Simon, M.D., M.Sc. Massachusetts General Hospital Boston, MA

1/22/2015. Royalties from Demos Medical Publishing. Learn how to. Mirela Simon, M.D., M.Sc. Massachusetts General Hospital Boston, MA Mirela Simon, M.D., M.Sc. Massachusetts General Hospital Boston, MA Royalties from Demos Medical Publishing Learn how to - plan a functional mapping procedure - perform and interpret central sulcus localization