9/30/2016. Advances in Epilepsy Surgery. Epidemiology. Epidemiology

Transcription

1 Advances in Epilepsy Surgery George Jallo, M.D. Director, Institute for Brain Protection Sciences Johns Hopkins All Children s Hospital St Petersburg, Florida Epidemiology WHO lists it as the second most common cause of mental health disability in young adults. North American prevalence: 5-10 / 1000 Surgery for temporal lobe epilepsy can be very effective, Reported seizure control rates of 60-70% but only ~1.5 % of eligible candidates (Wiebe et al., Engel et al.) undergo surgery in the United States Epidemiology Mesial temporal lobe epilepsy is the most frequently encountered adult chronic partial epilepsy (60-75%). Frontal lobe epilepsy (5-15%) include primary motor, supplementary motor, complex automatisms, speech arrest. 30% of patients undergoing surgery have a structural lesion (focal encephalomalacia, tumor, malformation, developmental anomaly.) In series of pediatric patients, cortical dysplasia or malformation account for 26% of seizure patients. 1

2 Candidates for Epilepsy Surgery Persistent seizures despite appropriate pharmacological treatment Usually at least two drugs, appropriate to seizure type, at adequate doses, with adequate compliance Impairment of quality of life due to ongoing seizures Loss of driving privileges, employment opportunities, social/cultural stigma, dependence on others, side effects of medications, under achievement in school, memory deficit, attention deficit, injuries, accidents S-Slide 4 Presurgical Evaluation History and Physical Exam Electroencephalography Imaging Presurgical Testing Neuropsychology Evaluation Comprehensive Patient Care Conference S-Slide 5 Patient Evaluation Scalp electrode monitoring, video EEG monitoring in an EMU. MRI to look for lesions, temporal lobe abnormalities. Interictal FDG-PET, looking for decreased metabolism in the interictal focus. Invasive monitoring strips, grids, depth electrodes. 2

3 Patient Evaluation Cortical mapping via fmri and cortical stimulation near eloquent areas, for language and motor mapping. The Wada test, for language lateralization, and memory usage. Neuropsychological evaluation for localization and outcome estimation. Imaging Studies Functional Imaging PET hypometabolism interictally SPECT hypoperfusion interictally hyperperfusion ictally PET and/or SPECT may be coregistered with MRI 3

4 Magnetoencephalography or MSI Magnetoencephalography (MEG) Magnetic source localization of interictal epileptiform discharges Functional mapping fmri has a good spatial resolution but provides poor temporal correlation, while EEG provides timed waveforms with poor localization. MEG jointly records these two signals providing spatially and temporally correlated images. S-Slide 11 Magnetic Source Imaging (MSI) Measures magnetic fields generated by electrophysiological activity Analyzes spatial distribution of magnetic field to localize its sources Overlays source locations onto anatomical image to create composite MSI image Provides noninvasive view of cellular function with high spatio-temporal resolution 4

5 MEG System 248 Channels Superior Temporal Resolution MEG-NYU Epilepsy Center Imaging for Surgical Candidates MRI- with epilepsy protocols T1-inversion prepared, gradient-echo, echoplanar, true inversion recovery image T-2- fast spin echo, FLAIR, 3D volume acquisition S-Slide 14 Presurgical Evaluation- MRI Right hippocampal sclerosis (arrow) S-Slide 15 5

6 Presurgical Evaluation- MRI Left mesial temporal sclerosis S-Slide 16 Presurgical evaluation - fmri fmri- language lateralization, hippocampus function, epileptogenic focus assessment Patient with left temporal lobe epilepsy. Left: Language mapping with verb generation task - activation in Broca s and Wernicke s areas. Right: Memory localization with picture encoding task - decreased activation in the left hippocampus. Invasive Monitoring 6

7 Invasive Monitoring ROSA with stereo EEG 7

8 Waves of the Future Treating Epilepsy with Stimulation Techniques Vagus Nerve Stimulation Two pilot studies (E01, E02), on a total of 14 humans in whom a programmable stimulating device (the NeuroCybernetic Prothesis [NCP]) was implanted (with 14- and 35-month followups), found the mean percentage of seizure reduction in the patients to be 46.6% 1994: the European Community approved the use of VNS for seizure prevention and control. Other controlled studies were performed, including the pivotal E : the US Food and Drug Administration (FDA) approved the use of VNS as an adjunctive treatment for refractory partialonset seizures in adults and adolescents older than age 12 years. Mode of Action Precise mode, like that of that of many antiepileptic drugs, is not known Activation areas: medulla, cerebellum, parabrachial nucleus, locus ceruleus, hypothalamus, thalamus, amygdala, hippocampus, cingulate gyrus. Inhibits seizures in multiple animal models of epilepsy Requires stimulation of C fibers, which desynchronizes the cortical EEG 8

9 VNS Therapy VNS Therapy VNS Therapy 9

10 Device Settings The efficacy of VNS improved significantly over the first year of long-term follow-up (7) However, for the group as a whole, improvement was not correlated with changes in device parameters. The original settings of 30 s on and 5 min off were indeed effective. However, in a subgroup of 26 patients who were highly refractory to VNS, a decrease in off time to 1.1 min was associated with a significant reduction in seizures. This finding is important, for it indicates that nonresponders may improve with a reduction in off time, or increase in duty cycle. Epilepsia Volume 42 Issue 8 Page August 2001 DBS for ATN Stimulation Sante Trial (Fisher et al.) DBS for ATN Stimulation Sante Trial (Fisher et al.) 10

11 Anterior thalamic nucleus stimulation Thought to activate global inhibitory influence. Might be better than VNS in certain classes of patients. 11

12 Other Stimulation Sites Dentate nucleus Chkhenkeli SA et al., Caudate nucleus Chkhenkeli SA et al., Subthalamic nucleus Benabid et al., Hippocampus Velasco et al., Cortical Surface Kinoshita et al., 2004; Lesser et al., Penfield and Jasper 1952, reported altering intraop ictal activity during mapping studies with brief pulses of stimulation. (Epilepsy and the Functional Anatomy of the Human Brain) Lesser RP, Neurol 1999;53:2073, noted possibility of stopping epileptic afterdischarges by stimulating near the hot lead with a brief adjacent pulse burst. Motamedi GK and Lesser RP, Epilepsia 2002;43:836, additionally discovered phase dependence to this abortive pulse, worked best at peak of local field potential. erns Multicenter Trial External closed loop system connected to implanted subdural strip monitors, 27 patients, 6 centers. Kossoff EH et al. Epilepsia 2004;45: hours of recording. On average 4 stims/hr/subject. 41% of patients demonstrated decreased sz freq and duration. Some patients benefited by tuning stim parameters, 4-8 ma current, μsec pulse width, 200 Hz stim, msec burst duration. 12

13 RNS Clinical Study RNS Clinical Studies Pivotal Study Design 13

14 Study Demographics Primary End-Point Long Term Reduction of Seizures n=230 14

15 Current RNS Trial Subjects with SPS or CPS w/wo GTCs Must have failed 2 med trials. Patients must have 4 sz s in 4 weeks for at least 8 weeks before implantation. No primary GTCs, VNS OK if off for 6 months. Neuropace Device Surgical Technique 15

16 Neuropace Device Visualase-MR Guided Laser Ablation Visualase utilizes a powerful image-guide system to target the affected area and to visualize thermal therapy in real time. Visualase workstation Small 980nm diode laser Integrated to MR Software: real-time thermometry, prediction model, and control features Laser Applicator Saline cooled 1.65mm in diameter 8 y.o with Gelastic Seizures 16

17 Laser Fiber Laser Fiber Target Area Pre Sagittal image T2 FLAIR hyper-intensity in hypothalamic hamartoma. Visualase Thermal image Low Watt test pulse confirms fiber placement Test pulse - 4.5W for 30sec Live Temperature Map Live Damage Estimate Sagittal Procedure Animation (not in real-time) Laser Dose 8W for 51sec Estimated Damage Area Sagittal 10.5mm by 10 mm Coronal 11.4mm by 9.2mm Temperature limits were set to protect the hypothalamus (above) and basilar artery and optic tract (below ). The limit near the hypothalamus shut the laser at 51 seconds. Coronal Procedure Animation (not in real-time) Target Area Irreversible Damage Estimate Ablation Pre-procedure T2 FLAIR Visualase Estimated Damage Image Post-procedure Contrast-enhanced T1 17

18 Target Area Irreversible Damage Estimate Ablation Pre-procedure T2 FLAIR Visualase Estimated Damage Image Post-procedure Contrast-enhanced T1 Visualase + Temporal Lobe Epilepsy Conclusions Surgery maybe best treatment for refractory seizures Unilateral focus Temporal location Lesional Consider early aggressive surgery in select patients There are minimally invasive surgical approaches to achieve seizure control 18