Extratemporal Nonlesional Epilepsy: Grids and Strips 11/30/2012

Transcription

1 Extratemporal Nonlesional Epilepsy: Grids and Strips 11/30/2012 Ashesh D. Mehta, M.D., Ph.D. Department of Neurosurgery Hofstra North Shore LIJ School of Medicine American Epilepsy Society Annual Meeting

2 Disclosure None American Epilepsy Society Annual Meeting 2012

3 Learning Objectives Understand how to use noninvasive testing to generate hypotheses and use grid, strip and depth electrodes to treat nonlesional epilepsy Recognize the value of grid electrodes in performing functional mapping Recognize the value of grid and strip electrodes to define network properties of the ictal onset zone. American Epilepsy Society Annual Meeting 2012

4 History 23 year old ambidextrous male Onset: age 12 Risk Factors: none Seizure Frequency: 1/month Semiology: consistent No auras Behavioral arrest, staring Head turn to the left Blinking Raises left arm secondary GTC amnesia

5 History (cntd.) Medications: LTG, ZNS Trials: LVT, OXC Goals: increase independence, complete culinary school Physical Exam: nonfocal

6 Video EEG, noninvasive interictal Bifrontal (R>L?) discharges

7 Video EEG, noninvasive interictal Cz montage

8 Video EEG, Ictal (transverse montage)

9 Video EEG, Ictal

10 Video EEG, Ictal

11 Normal MRI

12 2FDG-PET Bitemporal hypometabolism (R worse than left)

13 Morphometric Analysis Intraindividual Statistical comparison to cohort of 25 normal patients Increased cortical thickness in dorsolateral frontal lobe Hippocampal Volumetric analysis: symmetric and normal

14 Neuropsychological testing / Wada Deficits in: Attention, executive functioning Visual memory Visual construction skills Preservation of: Fine motor/dexterity Language Verbal memory Wada Left memory 11/12 after right injection Right memory 7/12 after left injection Bilateral language (L>R) with automatic speech and naming preserved after left injection.

15 Presurgical Conference Medication-resistant epilepsy Video EEG right sided onsets with broad field Frontal lobe involvement -- temporal onset? PET Right (temporal) sided abnormality Neuropsychological testing Evidence for frontal (executive) and right temporal (visual memory) dysfunction Wada memory suggestive of greater right temporal dysfunction Wada/fMRI language raises concern about right sided language

16 Plan Plan: Frontotemporal grid for language mapping and determination of location and extent of ictal onset zone Strips to cover frontal pole, orbitofrontal cortex, interhemispheric fissure, inferior temporal and temporal pole Depth electrodes into amygdala, hippocampus and supplementary motor area.

17 Implantation A M L P Right frontotemporal craniotomy for implantation of 64 channel grid, multiple strip electrodes and depth electrodes into hippocampus, amygdala and supplementary motor area

18 fmri coregistered to implant Grid centered over the frontotemporal area Hand Motor area at posterior superior aspect of grid Frontal: Interhemispheric, orbital and dorsolateral Temporal: Mesial, inferior and lateral temporal coverage

19 Depth Electrodes to Sample Mesial Structures Use of Frameless Stereotaxy to implant electrodes into mesial temporal and mesial frontal structures

20 Invasive EEG Interictal Anterior/ Superior Grid Superior Frontal Strip

21 Invasive EEG, interictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths Broad discharges across posterior frontal strip and anterior superior grid

22 Invasive EEG, interictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths

23 Invasive EEG, HFO Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths

24 Invasive EEG, Ictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths Interictal/Preictal Repetitive Discharges

25 Invasive EEG, ictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths Attenuation and discharges from anterior frontal strips and anterior frontal aspect of grid. Minimal behavioral correlate.

26 Invasive EEG, Ictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths

27 Invasive EEG, Ictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths Significant evolution in anterior frontal strips and anterior frontal aspect of grid prior to head turn Left head turn

28 Invasive EEG, Ictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths Head turning to left Bilateral Hip abduction and flexion Left hand extension, elbow flexion Bilateral clonic jerking

29 Invasive EEG, Ictal Frontal Grid Temporal Grid Frontal Strips Temporal Strips Depths Spread to occipitoparietal strip

30 Seizure spread pattern 1. RFP 1,2 2. G1-3, 9-11, 17-19, 25-27, RFM RFA2-4

31 Coherence in slow fluctuations of gamma power at rest Seed Coherence maps calculated with seed in midfrontal strip (left) and anterior frontal grid electrode (right). Slow (0.1-1Hz) fluctuations of gamma power reveal a pathological network that includes anterior dorsolateral frontal, orbitofrontal, and anterior mesial frontal areas.

32 Cortico-cortical evoked potentials Stimulated electrodes Significant CCEP response No CCEP response Stimulation performed at ictal onset electrodes in mesial frontal strip Highlights frontal network

33 Resting fmri Connectivity Analysis IOZ Seed Ictal onset electrodes entered as a seed for analysis of functional connectivity based upon correlated spontaneous BOLD fluctuations in preoperative fmri Addresses sampling issue Reminiscent of the default mode network, but a larger region of the dorsolateral frontal cortex is highlighted

34 Electrical Stimulation Mapping Cleared for language and motor Cleared for motor Resection Lower extremity motor Upper extremity motor Upper extremity motor (complex) Face motor Cleared for language in inferior frontal lobe Confirmation of supplementary motor area

35 Example of Dominant Hemisphere Electrical Stimulation Mapping Results (different patient)

36 Postoperative Followup Pathology: Cortical Dysplasia Type 2b Cytomegalic neurons White matter neuronal heterotopia Seizure-free at 6 months. No neurological deficits

37 Impact on Clinical Care and Practice Exploratory for localization when lateralization is clear Functional mapping Good for exploring network properties Depth electrodes may be supplemented Main Disadvantages: morbidity/discomfort patient willingness to proceed

38 Acknowledgements Comprehensive Epilepsy Center Hofstra North Shore LIJ School of Medicine Cynthia Harden, MD Sanjay Jain, MD Sean Hwang, MD Scott Stevens, MD Sarah Schaffer, PhD Deborah Risbrook, NP Laboratory of Multimodal Brain Mapping, Feinstein Insitutute for Medical Research David Groppe, Ph.D. Stephan Bickel, M.D., Ph.D. Pierre Megevand, M.D. Corey Keller, B.S. Laszlo Entz, M.D., Ph.D. William Ottowitz, M.D.

39 Algorithms in the Diagnosis and Treatment of Epilepsy Debate 2: Surgical Planning for Extratemporal Nonlesional Surgery? November 30, 2012 François Dubeau, MD Montreal Neurological Hospital and Institute, McGill University, Montréal, Canada American Epilepsy Society Annual Meeting

40 Disclosure No disclosure American Epilepsy Society Annual Meeting 2012

41 Learning Objectives To review decision making process for presurgical planning; To discuss of the indications and utility of invasive intracranial EEG in preoperative assessment. American Epilepsy Society Annual Meeting 2012

42 Pre-surgical strategy - principles Diagnosis of intractable epilepsy and disabling seizures, and no contraindications; Demonstration that the EZ lies within a well defined resectable cortical tissue; and delineation of the extent of the pathological area and of the eloquent/vital tissue; There is no single test that provides complete and definitive information; no clinical evaluation or technique used to evaluate patients for surgery as high sensitivity or high specificity. Therefore different tests are combined in order to form a hypothesis regarding the location and extent of the EZ. They are also necessary to measure the impact of surgery on brain function. 42

43 Non lesional extra-temporal lobe epilepsy case report SA. 33 yo R-handed man, electrical engineer, with seizures since age 16: Obstetrical history was uneventful. No past medical and surgical antecedents. No family history. Normal development and IQ; Seizures started at 16 and rapidly became refractory. Typically, nocturnal or sleep-related, in clusters, of short duration, and followed by immediate recuperation; 1 o VAP, 2 o PTH ( LFTs), 3 o CBZ (allergic skin rash), 4 o LEV LEV + GBP LEV + GBP + PB LEV + TPM. 43

44 Non lesional extra-temporal lobe epilepsy case report cont`d Seizure semiology Arousal, possible aura, poorly defined, duration 10 to 20s: stares briefly, discreet tonic posture, blinking, pout, occasional H and E to L, immediate or almost immediate recuperation, goes back to sleep. Amnestic. Important fatigue next morning, occ. 2ary G. Seizures are frequent, mostly nocturnal, in clusters but with questionable disability. 44

45 Non lesional extra-temporal lobe epilepsy case report cont`d 1st admission PHASE 1 (2010) normal phenotype and neuro examination, no interictal scalp discharges (10-20 and systems), 30 brief typical seizures recorded, mostly nocturnal, non-localizing nor clearly lateralizing normal MRI, R-handed and L hem. speech dominance, neuropsychology profile consistent with bilateral FL dysfunction, and normal TL function, FDG-PET showed mild R T hypo-metabolism, 45

46 SA. Typical clinical seizure and scalp EEG onset. arousal C3-P3 C4-P4 1 s

47 SA. Normal routine 3T MRI, flair sequences (2010). coronal sagittal R

48 SA. Interictal FDG PET: mild, questionable R TL hypometabolism R AC-PC alignement Hippocampal axis

49 Non lesional extra-temporal lobe epilepsy case report cont`d 2nd admission PHASE 2 (2012) Results of PHASE 1 evaluation: frontal lobe semiology, not clearly lateralizing, no interictal scalp discharges and bilateral ictal discharges, bilateral FL cognitive interferences, no SPECT (brief seizures) and no EEG/fMRI (no interictal EA), interictal FDG PET, mild R TL hypometabolism. 49

50 SA. 1st intracerebral depth electrodes implantation scheme proposal: - exploratory - bilateral - mesial and cortical aspects of FT structures, R > L. ant cing mid cing ant frontal orbito-frontal post cing, pre-cuneus Am Hc ant cing mid cing post cing, pre-cuneus Hc Right

51 Non-lesional focal epilepsy The most common histopathological finding in surgical specimens obtained from patients with nonlesional focal epilepsy is FCD; To histopathological FCD abnormalities correspond measurable MRI features: thickening of the cortex gray and white matter signal changes blurry gray-white matter boundary transmantle sign.

52 SA. Post-processing MR images (2012) Flair R R Gradient map Relative intensity map R R

53 SA. Surface-based analysis intensity gradient (blurring) z-score z-score Composite z-score thickness manually segmented FCD lesion (volume: 1,713 mm 3 )

54 Voxel-based morphometry and intensity analysis: improving signal-to-noise and contrast-to-noise ratios From Andrea and Neda Bernasconi SA right

55 from E Kobayashi SA. EEG/MEG acquisition with 53 EEG electrodes and 271 MEG sensors: - very frequent low amplitude MEG spikes R FC - rare slow sharp waves at FC2, FC4, F2 and F4 MEG spikes (n = 58) source localization along the averaged spike peak

56 SA. Concordant findings between surface base analysis and MEG source localization. Surface-based analysis MEG spikes source localization Composite z-score Composite z-score

57 Non lesional extra-temporal lobe epilepsy case report cont`d 2nd admission PHASE 2 (2012) Results of PHASE 1 evaluation - bis: frontal lobe semiology, not clearly lateralizing, no interictal scalp discharges and bilateral ictal discharges, bilateral FL cognitive interferences, interictal FDG PET, mild R TL hypometabolism, but MEG demonstrated R FL source, MRI (3T) repeated with post-processing analyses revealed an area of FCD over the R mid F convexity, in a non-eloquent cortical region. 57

58 SA. 1st intracerebral depth electrodes implantation scheme proposal: - exploratory - bilateral - mesial and cortical aspects of FT structures, R > L. ant cyng mid cyng ant frontal orbito-frontal post cyng, pre-cuneus Am Hc ant cyng mid cyng post cyng, pre-cuneus Hc Right

59 SA. 2nd intracerebral depth electrodes implantation scheme proposal: - confirmatory - bilateral - peri-lesional and R FT structures. Right lesion sup ant cyng lesion inf ant cyng mid cyng orbito-frontal Am Hc

60 interictal orbitofrontal anterior cing. mid cing. lesion sup. lesion inf. Am Hc 1 s

61 ictal orbitofrontal anterior cing. mid cing. lesion sup. lesion inf. Am Hc 1 s

62 Non lesional extra-temporal lobe epilepsy case report cont`d 2nd admission PHASE 2 (2012) Invasive EEG with intracerebral depth electrodes provided confirmatory results: continuous or near-continuous focal interictal polyspike activity; several typical seizures spontaneously recorded also with focal onset; neuro-stimulation: - low frequency stimulations (1 Hz, 2msec, 30s): no response, - high frequency stimulations (50 Hz, 1msec, 5s): AD and typical clinical manifestations at 0.8 ma with stimulations of the lesional and peri-lesional contacts. 62

63 No. of patients (1) To define seizure generator and EZ, and to tailor surgical resection Seizure semiology EEG Structural imaging Neuropsycho. medication surgery

64 No. of patients (1) To define seizure generator and EZ, and to tailor surgical resection Seizure semiology EEG Structural imaging Neuropsycho. Functional imaging Post-processing MR imaging MEG (2) EEG/fMRI quantitative structural MRI methods demonstrate an increased diagnostic yield of epileptic lesions, and provide better options to patients with 'cryptogenic' epilepsy (Bernasconi et al., Nat Rev Neurol 2011; Epilepsia 2011); EEG/fMRI help to delineate the epileptic focus, and to understand neuronal networks related to focal discharges (Pitau et al., Neurology 2102 and Fahoum et al., Epilepsia 2012). medication surgery

65 EEG/fMRI help to delineate the epileptic focus, and to understand neuronal networks related to focal discharges Moeller et al., Neurology F8 spikes related-bold response showed an activation over the lateral R OF region overlapping an occult FCD.

66 EEG/fMRI help to delineate the epileptic focus, and to understand neuronal networks related to focal discharges Fahoum et al., Epilepsia Group analysis results of TLE patients (n=32).

67 No. of patients (1) To define seizure generator and EZ, and to tailor surgical resection Seizure semiology EEG Structural imaging Functional imaging Post-processing MR imaging MEG (2) EEG/fMRI (3) Intracranial EEG Neuropsycho. medication considered when there is evidence for conflicting results, lack of concordance or incomplete information between clinical picture, neuropsychological and imaging data: surgery

68 Impact on Clinical Care and Practice indications for invasive EEG monitoring: Invasive EEG is not required in lesional focal epilepsy when exists congruent seizure semiology, EEG findings and cognitive evaluation; Invasive EEG is considered when there is a need to define more accurately the spatial-temporal organization of the epileptic discharge at onset and during propagation; Invasive EEG may be confirmatory or exploratory, and may be used to study the focus/lesion relationship; Invasive EEG cannot be a fishing expedition, and should not be considered in the absence of a good hypothesis.

69 Impact on Clinical Care and Practice conditions where invasive EEG would be indicated: In non-lesional focal epilepsy, or to define a deep-seated epileptic generator localized in buried structures inaccessible to scalp EEG (in which cases intracerebral EEG probably provides a better sampling), or to determine relationship between EZ and lesion (overlap, peri-lesional or remote); In multifocal epilepsy e.g. bilateral TLE, or in multifocal or diffuse lesions with however congruent semiology and scalp EEG findings. For functional mapping when EZ overlaps with eloquent cortex (cortical electrodes and grids are better suited for mapping of cortical function);

70 Impact on Clinical Care and Practice factors that would exclude invasive EEG: No clear hypothesis about the localization of the EZ; Generalized or diffuse epileptiform abnormalities on scalp EEG, or multifocal epilepsy; Risks for unacceptable complications due to eloquent cortex, or risks for unacceptable complications due to medical conditions.

71 Intracerebral EEG methods and characteristics: advantages and disadvantages Type Recording areas Advantages Disadvantages Intracerebral depth electrodes (within cortex) Deep limbic and paralimbic buried structures: Am, Hc entorhinal cortex and parahc, and insula; interhemispheric cortical structures; depth of the sulci; hypothalamus, thalamus and basal ganglia; deep-seated and peri-ventricular lesions. Good sampling of deep structures; findings can be standardized in a common stereotaxic space allowing inter-subject comparisons; and low morbidity. Limited sampling of neocortical structures; not adapted for exhaustive cortical functional mapping. Grids (subdural surface) Cortical convexity, basal and interhemispheric neocortical surface. Broad coverage of neocortical areas; wellsuited for mapping of cortical function by electrical stimulation. Large craniotomy and higher morbidity; no good sampling from deep buried structures; needs to be immediately followed by resective surgery. Strips (subdural surface) Cortical convexity, basal and interhemispheric neocortical surface. Good coverage of neocortical areas; low morbidity. No good sampling from deep buried structures.