Surgical Management Of Medically Intractable Temporal Lobe Epilepsy By Amr Farid Lecturer Of Neurosurgery Mansoura University

Why we should help? Quality of life Physical injury Neuropsychological functions impairment Psychiatric problems Sudden unexpected death in epilepsy Complications of AEDs (Inexperienced prescriptions)

Introduction

Seizure classification: Introduction Seizure classification: 1. Partial seizures A) Simple partial seizure Motor Sensory Autonomic Psychic B) Complex partial With simple partial onset Without simple partial onset, altered awareness / memory from the onset C) Partial seizures (simple or complex) evolving to secondary generalization

2. Primary generalized (convulsive or nonconvulsive) Introduction 2. Primary generalized (convulsive or nonconvulsive) Absence seizures. Myoclonic seizure Clonic , tonic and tonic-clonic seizures Atonic seizures 3. Unclassified seizures 4. Prolonged or repetitive seizures (status epilepticus)

Mesial and Neocortical Temporal Epilepsy Clinical Features Introduction Introduction Mesial and Neocortical Temporal Epilepsy Clinical Features NTLE MTLE Warning symptoms localized to the epigastrium ,throught, or chest with or without fear. Initial motionless staring oro-alimentary masticatory or swallowing automatisms with or without repetitive manual automatism Seizures are significantly longer in duration (> 1 minute). Ipsilateral automatisms followed by contralateral dystonic posturing. A phenomenon of dreamy state with memory of past scenes (déjà vu ) Auditory hallucinations Early contralateral dystonic posturing. Rapid spread to suprasylvian area produce versive and colonic motor movement of head ,eye and face.

Localization of Partial Seizure Focus Introduction Localization of Partial Seizure Focus 20% 10% 70% This is the most common type of adult-onset epilepsy. Causes such as hippocampal sclerosis, low- grade tumors and cortical dysplasias , vascular malformation

Pre-operative Assessment Electro physiologically Introduction Pre-operative Assessment Electro physiologically Electroencephalography (EEG) Continuous Video EEG Value OF EEG Diagnostic tool Spikes , poly spike Sharp wave Sharp and slow waves complexes.

Limitations of EEG: Introduction Normal EEG findings do not exclude epilepsy. The initial EEG may show normal results in 50% of cases. Increasing the duration of recording. Deep focus. Artifact

(A) Non invasive electrodes Introduction Electrode Placement (A) Non invasive electrodes 1- Scalp Electrodes: Standard 10-20 system. 2- Zygomatic and Periorbital Electrodes: (Anterior temporal foci)

The international 10-20 electrode system Introduction The international 10-20 electrode system

(B) Semi-invasive Electrodes Introduction (B) Semi-invasive Electrodes Nasopharyngeal Electrodes: mesial temporal and orbitofrontal foci. Sphenoidal Electrodes: for long term ,with less artifacts. Foramen Ovale Electrodes: mesio­basal temporal lobe epilepsy. Tympanic Electrodes: middle or posterior basal temporal regions

(C) Invasive Electrodes Introduction (C) Invasive Electrodes Epidural Electrodes Subdural Strip and Grid Electrodes Implanted Intracerebral Electrodes (Depth Electrodes) Seizures are lateralized but not localized (eg, a left-sided). Seizures are localized but not lateralized (eg, both temporal lobes). Seizures are neither localized nor lateralized (eg. diffuse ictal). Seizure localization is discordant with other data Intraoperative , ECoG

Partial Onset Seizure – Left TLE Introduction Partial Onset Seizure – Left TLE Generalized Onset Seizure

Origin Of EEG abnormality Introduction Generalized Focal to generalized Focal Origin Of EEG abnormality

Neuroradiology Functional Magnetic Resonance Imaging (fMRI): Introduction Neuroradiology Functional Magnetic Resonance Imaging (fMRI): PET and SPECT imaging especially has shown both increased glucose metabolism and blood flow respectively in the epileptic cortex, which is depressed in the post-ictal and interictal states. MRS is a newer tool that demonstrates regional metabolic alteration in epileptogenic tissue. Magnetoencephalography: Measurement of extracranial magnetic fields

Imaging issues: strategies for successful interpretation Introduction Cutting planes Imaging issues: strategies for successful interpretation (HIPPO SAGE)

MRI features of HS Introduction Secondary signs Primary signs Unilateral atrophy of the mamillary body, fornix ,amygdala. Increased T2 W signal in ant. temporal white matter with loss of grey-white demarcation in the ipsilateral anterior temporal lobe. Unilateral dilatation of the temp. horn. Primary signs Atrophic unilateral hippocampus . Hyperintensity on both T2 W and FLAIR images Loss of the hippocampal internal architecture and that of normal digitations of the head.

MRI-PET fusion image (Lt TLE) Introduction Functional and Morphologic Data Fusion for Epileptogenic Foci Localisation MRI +SPECT (Lt TLE) MRI-PET fusion image (Lt TLE)

Scheme for preoperative evaluation in TLE Introduction Scheme for preoperative evaluation in TLE

Surgical Treatment of TLE Introduction Surgical Treatment of TLE General Surgical procedures: Resection techniques is simple excision of the structural lesion Disconnection techniques (hippocampal transection ) Augmentation techniques ( vagal stimulation). Gamma knife radiosurgery Stereotactic radiofrequency ablation techniques .

Introduction Epileptic Zones

Introduction Temporal Lobectomy: Temporal lobe resection produces a seizure-free state in 60% to 80 % of patients: Anterior temporal lobectomy (ATL) is the most common surgical procedure performed in adolescents and adults. Selective Amygdalohippocampectomy for patients with MTLE

Introduction Temporal Lobectomy: A) Anterior temporal lobectomy with amygdalo-hippocampectomy

B) Selective Approaches to The Mesial Temporal Area Introduction B) Selective Approaches to The Mesial Temporal Area

Trans-sylvian approach Introduction Trans-sylvian approach

Meyer’s loop Introduction Risk for superior quadrant hemianopsia 50 –100% after standard temporal lobectomy up to 50% after trans-sylvian selective amygdalohippocampectomy

Introduction

Aim Of The Work

This study is to compare: seizure and neuropsychological outcomes after: Anterior temporal lobe resection plus amygdalo-hippocampectomy (AH) versus selective amygdalo-hippocampectomy (AH) through trans sylvian approach In the treatment of medically intractable temporal lobe epilepsy

Patients & Methods

Patients & Methods This study was conducted on 24 patients with medically intractable Temporal Lobe Epilepsy at Tohoku University Hospital.

Inclusion criteria Exclusion criteria Patients & Methods Medically intractable epilepsy due to identified temporal lobe focus. Lesions may be intra or extra axial within the anatomical confines of the temporal lobe. Both of neocortical and mesial temporal lobe. Exclusion criteria Patients unfit for surgery. Presence of multiple brain lesions. Pure extratemporal epileptogenic zone.

Presurgical evaluation Patients & Methods Presurgical evaluation Drug resistant epilepsy : failure of two tolerated, appropriately chosen (whether as monotherapies or in combination) to achieve sustained seizure freedom over period of two years. Detailed history :patients and close contact. Clinical assessment Electrophysiological assessment via ( VEEG). Neuroimaging via routine MRI brain ,(FDG-PET), Interictal SPECT and magneto-encephalography (MEG) were done to confirm diagnosis.

Neuropsychological Test Battery Patients & Methods Neuropsychological Test Battery Wechsler Adult Intelligence scale (WAIS-R: VIQ, PIQ, FIQ) and Wechsler Memory Scale (WMS-R: verbal , non verbal ,full memory) pre-operative and one year post operatively. Changes or discrepancy of the score greater than 10 was defined as significant improvement ,changes within 10 defined as no significant changes and if lower than 10 will be considered impairment . Also difference between Verbal and non verbal memory scores pre-operatively greater than ten was defined as verbal dominant memory impairment and vice verse or less than ten difference shows non significant laterality.

Case example Patients & Methods Pre-op Post-op Post-op gains or declines WMS-R Verbal memory 63 → 75 Non-verbal memory 82 → 83 Significant gain No change Pattern of memory impairment Verbal dominant VDMI No dominancy

(b) Procedures Patients & Methods Operative Techniques: Two groups of patients enrolled into the study: Group (A): Anterior temporal Iobectomy and amygdalo-hippocampectomy (14 patients). Group (B): Selective amygdalohippocampectomy (AH) through trans-sylvian approach (10 patients). Post operative Histopathological Studies

Patients & Methods (c) Patients' follow up All patients will be followed up for 1-2 Years after the procedure via: Seizure frequency every 1 month (Engel class.) Neurological examination Neuropsychological (WMS ,WAIS)R. Radiologically by MRI Electro-physiologically by inter-ictal EEG. All the patients will be kept on anti epileptic drug regimen throughout the follow up period. Statistical methods Data were analyzed using JMP software, version 11

Results

Results Preoperative status: Age: ranged from 19 to 53yrs with mean of 34.8yrs and standard deviation of 10.9yrs

Demographic data and febrile seizure history in both groups Results Demographic data and febrile seizure history in both groups Type of surgery ATL/AH SAH 14 10 No. 32.8 37.7 Age (Y) Mean 9.7 12.3 Std. Dev Sex 9 8 F 5 2 M 10.3 17.8 Epilepsy onset (Y) 7.1 Handedness 1 L 13 R Associated conditions 7 Febrile Seizure Meningitis, Febrile seizure 3 No associated conditions

Seizure semiology Results N % of Total Seizure semiology 5 20.83% Abdominal aura >Automotor seizure Abdominal aura >Automotor seizure >GTC 1 4.17% Abdominal aura >Dialeptic seizure >Rt face clonic seizure Automotor >GTC Automotor seizure 2 8.33% Complex motor seizure Complex motor seizure >Lt body clonic seizure Dialeptic >GTC Dialeptic >Rt oro-facial/arm clonic >GTC Dialeptic seizure

Preoperative pattern of memory impairment and side of the Temp. focus Results Preoperative pattern of memory impairment and side of the Temp. focus

The pre operative WMS-R scores Results The pre operative WMS-R scores The left TLE group performed worse than right TLE group on verbal memory. But for demonstration of the pre operative non verbal memory scores were not so confirmatory

Results Seizure Outcome Engel classification

Results Seizure outcome in Engel classification according to the type of surgery Majority of patients shows better seizure outcome after Temporal lobe epilepsy surgery. Engel class IA (79% ATL/AH, 70% SAH), Engel II A (14% ATL/AH &10% SAH) Engle IIB (7% ATL/AH and 10% SAH) and (10%Engle IID with SAH group).

Seizure outcome and the duration of epilepsy Results Seizure outcome and the duration of epilepsy Better Engel class with patients who have shorter duration while worse control in patients with longer period (25% Engel class I, 30-36yrs),(75% Engel Class I, 8-13yrs).

Results Age of patients and seizure outcome Young age group (19-23Y) shows 83% Engel class lA while older group (46-53Y)shows lower outcome (67% Engel class. lA)

Neuropsychological outcome Results Neuropsychological outcome Intelligence Quotient (IQ) Significant improvement in full IQ after surgery (43% ATL/AH and 30% SAH) groups with minimal impairment percent (7% ATL/AH) but the majority of patients shows no significant difference in pre-post operative Full IQ scores (50% ATL/AH and 70% SAH).

Postoperative memory changes Results Postoperative memory changes WMS-R / Verbal Memory

WMS-R / Non Verbal Memory Results WMS-R / Non Verbal Memory

Matched Pairs Results P Neuropsychological Evaluation Preoperative Postoperative P Mean SD WAIS-R: FIQ 78 21.04 86 22.74 < 0.0001* WMS-R: verbal 74.8 22.95 82.2 22.8 0.0027* WMS-R: visual 89 17.2 93.7 18.5 0.0586 WMS-R: full 75.9 22.06 83.5 22.47 0.0029*

Results P Neuropsychological Evaluation Preoperative Postoperative   Mean SD WAIS-R: FIQ 77.71 19.73 85.85 20.46 0.00258* WMS-R: verbal 74.07 20.73 77.29 19.79 0.18 WMS-R: visual 90.86 15.43 91.36 18.68 0.45 WMS-R: full 75.14 20.04 78.36 19.53

Results P Neuropsychological Evaluation Preoperative Postoperative   Mean SD WAIS-R: FIQ 78.5 23.87 86.1 26.76 0.0103* WMS-R: verbal 75.7 26.90 89 25.95 0.00026* WMS-R: visual 86.5 20.01 96.9 18.66 0.0071* WMS-R:full 76.9 25.73 90.6.5 25.5 0.00047*

Pathological findings Results Pathological findings N % of Total Pathology 1 4.17% Cavernous malformation 2 8.33% Ganglioglioma 17 70.83% HS 4 16.67% HS, CD Pathological findings and surgical approaches Type of surgery Pathology Cavernous malformation Ganglioglioma HS HS, CD N Lesionectomy + ATL/AH 1 ATL/AH 10 3 13 Lesionectomy+SAH 2 SAH 7 8

Pathological findings seizure outcome Results Pathological findings seizure outcome

Complications of surgery Results Complications of surgery

Case Presentation

Case No 1 45yrs old right-handed female Onset of epilepsy: 13y.o. Semiology: Automotor seizures MRI: Lt medial temporal non-enhanced lesion EEG: (ictal) Lt temporal, (interictal) FDG-PET: Lt medio-basal temporal hypometabolism Neuropsychology: Impaired verbal memory (WMS-R verbal 55 vs visual 78) One year post operative neuropsychology: significant improvement. Epilepsy diagnosis: Lt temporal lobe epilepsy Lt medial temporal lesion Procedures: Lt fronto-temporal craniotomy Selective :Lesionectomy Amygdalo-hippocampectomy Intra-operative EEG

Case No 1 EEG examination consistent with left temporal epileptogenic dysfunction.

Preoperative MRI T1 (axial) cuts shows left temporal lesion. Case No 1 Preoperative MRI T1 (axial) cuts shows left temporal lesion.

Case No 1 FDG-PET-MRI fusion

Hippocampal volumetry Case No 1 Hippocampal volumetry

Postoperative T2 axial MRI Case No 1 Postoperative T2 axial MRI

Case No 2 48 years old right-handed female. Etiology: Hippocampal sclerosis Onset of intractable seizures: 7 y.o. Semiology: Aura > Loss of awareness MRI: Lt hippocampal atrophy EEG: (ictal) Lt temporal onset, (interictal) Lt temporal spikes . FDG-PET: Lt mesio-basal temporal hypometabolism Neuropsych: Impaired verbal memory (WMS-R verbal 82 vs visual 104) Epilepsy diagnosis: Lt mesial temporal lobe epilepsy Post operative Engel class. I , significant improvement of verbal memory Procedures: Left Anterior temporal lobectomy Amygdalo-hippocampectomy

Case No 2 EEG examination consistent with left ant. temporal epileptogenic dysfunction.

Preoperative MRI (coronal) cuts Case No 2 Preoperative MRI (coronal) cuts

Hippocampal volumetry Case No 2 Rt hippocampus: 3.49 cm3 Lt hippocampus: 2.03 cm3 FDG-PET-MRI fusion Hippocampal volumetry

ECoG confirmed epileptic spikes in the anterior temporal cortex Case No 2 Maximum amplitude spikes ECoG confirmed epileptic spikes in the anterior temporal cortex

Case No 2 Post operative MRI

Case No 3 21 year old, right-handed male Onset of epilepsy: 13 years old Seizure frequency: Monthly Associated condition: Hx. of febrile seizures MRI: Rt hippocampal atrophy Seizure symptoms: Automotor , GTC Ictal EEG: Rt anterior temporal onset Interictal EEG: Rt anterior temporal spikes (BESA analysis) FDG-PET: Rt medial temporal hypo-metabolism IMZ-SPECT: Reduced uptake in Rt antero-mesial temporal Neuropsych: Low IQs, impaired verbal and non verbal memory ( postoperative significant improvement) Epilepsy diagnosis: Rt mesial temporal lobe epilepsy Post operative Engel class. I   Procedures: Right Trans-sylvian selective amygdalo -hippocampectomy Intra-operative EEG

BESA Epilepsy Report analysis of EEG Case No 3 BESA Epilepsy Report analysis of EEG Rt temporal Epileptogenic dysfunction

Hippocampal volumetry Case No 3 Preoperative MRI (STIR, FLAIR) Hippocampal volumetry

FDG-PET-MRI coregistration Case No 3 FDG-PET-MRI coregistration

Post operative MRI Case No 3 Hippocampus Head Fimbria Parahippocampal gyrus Post operative MRI

Conclusion

conclusion Temporal lobe epilepsy (TLE) is the most common focal. Hippocampal sclerosis (HS) its major pathological substrate. Risk factors for post operative cognitive decline after surgery TLE surgery effective for intractable epilepsy with 70-80% favorable seizure outcome Goals of surgery is to abolish the seizures and avoid any neurologic deficits . A secondary goal, in cases of tumors and vascular malformations is to entirely remove