Surgical Treatment of Epilepsy

Transcription

1 Presurgical Assessment and the Surgical Treatment of Epilepsy Michael C., MD Director, Rush Epilepsy Center Associate Professor and Senior Attending Neurologist Rush University Medical Center Chicago, Illinois Surgical Treatment of Epilepsy Patient selection Diagnostic evaluation for surgical treatment Types of surgical treatment Outcomes of therapy: risk/benefit Seizure freedom/cognitive function 1

2 Partial Epilepsy Goals of Therapy Render patient seizure-free Avoid neurological morbidity Improve quality of life Participating and productive member of society Epilepsy Surgery Surgical Candidates Medically refractory seizures Physically, socially disabled Localization-related epilepsy Low risk for morbidity Potential for rehabilitation 2

3 Partial Epilepsy Focal or GTC Seizures > 1 million patients in US 90% of the adult incident cases 45% have medically refractory seizures 20% have intractable epilepsy Partial Epilepsy 80% of adult partial epilepsy is of temporal lobe origin 90%: amygdalohippocampal complex origin (MTLE) 10%: lateral a temporal neocortex e origin (neocortical epilepsy) 3

4 Partial Epilepsy Comorbidity Cognitive disorder: memory loss Psychological illness: variable expression and intensity Psychosocial debilitation Increased risk of morbidity and mortality Epilepsy Surgery Misperceptions Should be of last resort Exclude the following: Bitemporal spikes GTC seizures Coexistent t psychiatric i illness Developmental delay 4

5 Evaluation of the Medically Intractable Patient: Questions Does the patient have epilepsy? Need to record with EEG the events in question Nonepileptic event Psychiatric or medical etiology Have the AEDs used been appropriate for the seizure type? Have adequate blood levels been tolerated and documented to prove that seizures are medically intractable due to lack of efficacy, not tolerability? Partial Epilepsy Treatment Old drugs (CBZ, Pb, PHT, VPA) New drugs (FBM, GBP, LEV, LTG, OXC, PGB, TGB, TPM, ZNS) Vagus nerve stimulation Epilepsy surgery 5

6 Epilepsy Efficacy of Treatment Brodie et al. Neurology 2002;58:S unselected patients newly diagnosed with epilepsy Followed for a median of 5 years Evaluate the efficacy of treatment (CBZ, VPA, LTG) Epilepsy 470 Newly Diagnosed, Untreated Seizure-free on 1 st N=222 (47%) monotherapy Seizure-free on 2nd N=61 (13%) monotherapy Seizure-free on 3rd N=6 (1%) monotherapy Brodie,

7 Epilepsy Efficacy of Treatment 63% were seizure-free the last year Only 11% who failed the 1st AED became seizure-free About 30-40% will have a difficult-tocontrol seizure disorder 0% seizure-free on > 3 AEDs Brodie, 2002 Partial Epilepsy Seizure-free on AEDs Partial epilepsy: 55% Temporal lobe epilepsy: 35% Lesional pathology: 10% Mesial temporal sclerosis: 10% 7

8 Epilepsy Surgery Historical Perspective Macroscopic pathology Extratemporal cortical resections Neurological deficits Ictal semiology Epilepsy Surgery Temporal Lobectomy: Pioneers Common operative strategy EEG localization Hippocampal resection Mesial temporal sclerosis Safe and effective procedure 8

9 Unified Theory of Epilepsy Surgery The surgical treatment of medically intractable epilepsy is to substantially disrupt a dysfunctional system But rarely do the interventions, whether resection, multiple subpial transection (MST), CCD, or VNS, completely remove or suppress the dysfunctional network Surgical Decision Making Focal resections First choice in appropriate candidates Importance of early intervention Palliative surgery (successful outcome does not always mean cure ) Vagus nerve stimulation (VNS) Corpus callosum division (CCD) Multiple subpial transection (MST) 9

10 Randomized, Controlled Trial of Surgery for TLE 80 patients randomly assigned for surgery (40 pts) or AED therapy (40 pts) for 1 year Four of the 40 pts refused surgery. Six of the 36 patients required invasive presurgical investigation Results free of seizures that impair awareness: 58% randomized to surgery 8% randomized to AED therapy 64% actually had surgery p<0.001 Wiebe S, et al NEJM Editorial Few accepted therapeutic interventions are as underutilized d as surgical treatment t t of epilepsy Two million patients suffer epilepsy in US 400, ,000 not controlled with AEDs 1990 survey: 1500 therapeutic surgical interventions Seizure-free rate: 70-90% surgical therapy Quality of life for patients with epilepsy treated surgically is related to the reoccurrence of seizures QOL higher employment/school attendance in SG Engel,

11 Practice Parameters: TLE Surgery Epilepsy: chronic neurologic disorder affects 0.5-1% of world s population In US and other industrial nations with many AEDs available, 30-40% of patients not adequately controlled WHO survey: disability from epilepsy accounts for ~1% of global burden of disease as measured by disability-adjusted adjusted life years (DALYs) This ranks third behind affective disorder and alcohol dependence among neurologic disorders. Comparable to worldwide burden due to lung and breast cancer Engel, et al Practice Parameters: TLE Surgery Surgical procedures for treatment of epilepsy p ~500 year ~1500 year ~3000 year Estimated that there are 100, ,000 potential surgical candidates in US Early intervention may prevent or reverse the psychosocial sequelae of continued seizures in children Engel, et al

12 Practice Parameters: TLE Surgery Surgical efficacy compared to results from randomized clinical trials of AEDs Same patients with intractable partial epilepsy Responder rate (50% reduction of seizure frequency) of 50% is a good response Few patients rendered seizure-free Best results: VGB 6000 mg/d: 54%RR Most AEDs lower RR Vagal Nerve Stimulator: 30-50% RR at 1 year Temporal Lobectomy Presurgical Evaluation Routine EEG MRI head seizure protocol Long-term EEG monitoring Visual perimetry Neuropsychometry Sodium amobarbital study 12

13 Temporal Lobe Epilepsy Complex Partial Seizure 13

14 Imaging in Epilepsy Surgically Remediable Syndromes Lesional epilepsy: tumor, vascular anomaly, malformation of cortical development Structural MRI Medial temporal lobe epilepsy: mesial temporal poa sceoss sclerosis Structural MRI, PET CT vs MRI CT Neonate <2 yr Acute insult MRI incompatible Acute hemorrhage Ca +2 MRI Partial seizure any age Focal fixed deficit Loss of prior control Resolution/details Axis variable T2 2D GRE for Ca +2 or hemosiderin Wieshmann,

15 Standard MRI vs Epilepsy Protocol: Surgical Patients (n=90) Specificity Sensitivity % % Non-expert reader 22 _ Expert reader, standard MRI 40 _ Epilepsy protocol 89 >90 von Oertzen, et al

16 Amygdala Entorhinal Cortex 16

17 Long Term Intracranial Monitoring. Subdural Grid Implantation: Functional Brain Monitoring: 17

18 Location of Temporal Speech Areas Temporal Lobectomy Concordant MRI, EEG Unilateral hippocampal atrophy Unilateral epileptiform discharges 94% achieve an excellent outcome 18

19 Epilepsy Surgery Comparative Study NEJM August 2, 2001 Randomized controlled study 80 pts with TLE London, Ontario, Canada Surgery effective (p< 0.001) 001) QOL favors surgery (p< 0.001) Wiebe, et al Temporal Lobectomy Efficacy Sperling et al. (Phil., PA) JAMA 1996;276: Long-term operative outcome (5 yrs) 62 of 89 pts (70%) seizure-free 18 of 89 pts (20%) significantly improved 19

20 Temporal Lobectomy Operative Outcome Radhakrishnan et al. (Mayo) Neurology 1998;51: Excellent outcome: 134 (77%) Seizure-free: 120 (69%) Operative complication: 2 (1%) Epilepsy Surgery Extratemporal Non-lesional MRI is normal Limitations of ictal EEG Less favorable outcome Increased morbidity 20

21 Frontal Lobectomy Operative Outcome Mosewich et al. (Mayo) Epilepsia 2000;41: patients Excellent outcome: 59% Abnormal MRI: 72% Normal MRI: 41% Surgical Decision-Making Conclusions A marvelous time to treat epilepsy p So many medical and surgical treatment options The pool of truly intractable seizure patients is actually getting smaller As few as 20% of patients may not achieve complete or almost complete control with current interventions 21

22 Longer Term Follow-up and AED Drug Withdrawal Lowe, et al., Epilepsia 2004 Mar 50 consecutive patients with MTS Mean F/U = 5.8 yrs 82% seizure free at 1 year 76% seizure free at 2 yrs 64% seizure free at 5 yrs No further recurrence beyond 5 yrs 29% of recurrence associated with withdrawal of meds Quality of Life Outcome Spencer, et al Neurology, Dec 2003 Multicenter study; 396 cases Compared to pre-op baseline, at 3 months QOL, anxiety, depression improved p< QOL was highly correlated with seizure outcome 22

23 Cost-Effectiveness Wiebe, et al, Journal of Epilepsy, p patients, intention-to-treat analysis projected over 35 years By year 8, surgery was more cost-effective in direct costs than medical treatment This does not take into account the effect on QOL and indirect costs Corpus Callosum Division Corpus callosum division is a palliative procedure to improve the seizure control of patients with medically intractable epilepsy who have no localizable, single surgically resectable lesion Developed by Van Waganen in Rochester, New York, in 1939, refined by Wilson at Dartmouth in the 1970s, and others to the present 23

24 Corpus Callosum Division: Patient Outcomes % of patients with drop seizures (as a primary indication) achieve a 50% or greater reduction in seizures 21-67% of those with tonic-clonic seizures (as a primary indication) have a >50% reduction Seizure-free rates range from 2-5% Indications for Multiple Subpial Transection MST may be used alone or more commonly with cortical resection MST is used when the epileptogenic zone originates in or overlaps eloquent cortex where a resection is precluded do to the expected functional loss Eloquent cortex includes primary sensorimotor cortex and speech cortex 24

25 Technique of MST Author, Year Efficacy of MST: Worldwide No. of Patients Significant Improvement Only MST MST & RES MST Only No Worthwhile Improvement MST & RES No. of Patients Neurologic Complications Shimizu et al Sawhney et al Zonghui, a - 18 a Wyler et al Mild motor (1) Hufnagel et al Pacia, Rougier et al Patil et al Rush Epilepsy Center TOTAL MST=multiple subpial transection; RES=resection a In this study, it was not clear whether MST alone versus MST-resection was performed. Type (No. of Patients) Mild speech deficits (2); mild motor deficits (3); overt speech deficits (2) Mild dysnomia (7); moderate dysphasia (1) loss of proprioception in hand (1) Permanent (7); transient (8); sensorimotor (13) 25

26 Neurostimulation for Epilepsy Responsive Neurostimulation (RNS) Trial Currently FDA trial ongoing at Rush Sponsored by Neuropace Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) Trial Currently FDA trial ongoing at Rush Sponsored by Medtronic Vagal Nerve Stimulation (VNS): FDAapproved for adjunctive treatment of epilepsy VNS Therapy Automatic intermittent stimulation Magnet use allows patient/caregiver Mild electrical pulses applied to the left vagus nerve in the neck send signals to the brain On-demand stimulation On-demand side effect control Simple in-office programming Assured compliance 26

27 Clinical Use: VNS Maximize current load Stimulation intensity (2-3 ma) On time (30 sec) Off time (1.8 min) Delay in maximal benefit months Decrease SE by decreasing stimulation frequency from 30Hz to 20Hz Clinical Impact: VNS Rush Series over 200 patients At 6 months ~ 35% responder rate At 1 year ~ 46% responder rate Postictal state decreased in the majority Severity of seizures improved in the majority Mood improved in the majority 27

28 Future Cortical stimulation Deep brain stimulation (DBS) Gamma knife (GK) Responsive Neurostimulation: RNS Feasibility Clinical Trial Ten epilepsy p centers in US Patients who are not surgical candidates due to the presence of 2 independent epileptic foci or where the epileptic foci involves eloquent cortex that cannot be resected due to unacceptable deficits Closed-loop system that stimulates only when the recognized pre-programmed pattern is recorded; implanted brain defibrillator 28

29 CT Scan Showing the Implanted Stimulator and Intracerebral Electrodes Right Sided Seizure with No Stimulation 29

30 Left-sided seizure detected by subdural electrodes Comparison of the ictal EEG response to increased therapeutic stimulation from 2.5 to4.5 ma Response to 2.5 ma Electrographic seizure that progressed to clinical CPS then GTC Response to 4.5 ma Electrographic and clinical response to therapeutic stimulation SANTE Study Design Multi-center Prospective Randomized Double-blind Parallel design 30

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32 Radiosurgical Treatment Conformal radiation directed at temporal portion of the amygdala, the anterior 2 cm of the hippocampus and adjacent parahippocampal gyrus Total volume within 50% isodose line between 5.5 and 7.5 cc Treatment isocenters: 2-6 Potential Risk of Radiosurgery for Epilepsy Risk of ongoing g seizures while waiting for radiosurgical effect (including sudden death from epilepsy) Neuropsychological deficits Language Memory Visual field defects Quadrantanopsia (relatively likely) Homonymous hemianopsia (in Europe with > 8 cc volume) 32

33 One Year Post Radiosurgery Two Years Post Radiosurgery 33

34 Typical Clinical Response Initial increase in auras with simultaneous decrease in complex partial seizures Headaches Radiological changes Conclusions Surgical treatment of epilepsy is effective and cost-effective ti in the appropriate patient t Evidenced-based data suggested that surgery is more effective than best medical care for TLE Radiosurgery appears effective for TLE Thalamic stimulation for multifocal epilepsy is being evaluated Responsive neurostimulation is an exciting novel treatment of intractable focal epilepsy when two or more foci are present; its clinical utility is being evaluated 34