Unnwongse 1

NEUROLOGY/2011/419796

APPENDIX e-1

METHODS

A systematic retrospective review of our surgical database and operative notes was carried out to identify all patients older than 12 years who underwent a standard anterior temporal lobectomy (ATL) by the same neurosurgeon (WEB) following intracranial EEG (ICEEG) with depth and subdural electrodes at the Cleveland Clinic Epilepsy Center between 1997 and 2008. We received approval from an ethical standards committee, the institutional review board, on human experimentation for any experiments using human objects. We received written informed consents, obtained from all patients (or guardians of patients) participating in the study. All patients underwent ICEEG with comprehensive extra-temporal subdural electrode coverage. Mesial temporal depth electrodes were implanted in these patients to ensure that the mesial temporal structures,the “usualsuspects” given their proclivity for epileptogenicity,were indeed not participating in the epileptogenic/seizure-sustaining network. Patients were included in this study if they fulfilled the following criteria:

(i)Atypical electro-clinical features of mTLE-HS, as defined by the 2004 ILAE report (1), and therefore not believed to have mTLE prior to their ICEEG investigation;

(ii)Seizure onset exclusively arising from the mesial temporal structures as documented by ICEEG; and

(iii)Post-operativeseizure freedom (Engel class I) for at least 3 years.

Data collection

Data collected included patient demographics, age at seizure onset and at surgery, handedness, seizure semiology, results of pre-operative and post-operative EEG, MRI, PET, ictal SPECT (if applicable), neuropsychological assessment, Wada test/fMRI (if applicable), pre-operative hypothesis, side of surgery, surgical pathology, and post-operative seizure outcome.

Electrophysiology techniques

EEG recordings were acquired using the 128-channel Lamont Vangard (Madison, WI) or 192-channel Nihon Kohden (Tokyo, Japan) systems (sampling rate 200 Hz, low filter setting 1 Hz and high filter setting 70 Hz). Noninvasive video-EEG monitoring was performed with scalp and sphenoidal electrodes placed according to the international 10–20 system. Interictal and ictal EEG data were analyzed by board-certified epileptologists. The semiological seizure classification system was used to systematically describe the seizure types in each patient (2).

Imaging techniques

The pre-operative MRI protocol, using 1.5T scanner (Siemens Medical Systems, Erlangen, Germany) consisted of sagittal T1, coronal fast T2, coronal FLAIR (5 mm thick with 2 mm inter-slices) and coronal MPRAGE (contiguous 2 mm thick) sequences. Post-intracranial electrode implantation CT scans were obtained and merged with pre-operative MRI data to compute a 3D reconstruction of the brain. Electrode positions were identified from a triplanar imaging display, and displayed on the surface reconstruction as a tessellated set of 2mm spheres, using proprietary in-house developed software. Pre-operative nuclear imaging studies included interictal 18Fluoro-2-desoxyglucose positron emission tomography scans (FDG-PET) and ictal-interictal single-photon emission computed tomography (SPECT) with Technetium-99m-labeled ECD (bicisate ethyl cysteinate dimer) usingthe subtraction image co-registered to the MRI technique (SISCOM).

Neuropsychological evaluation and Wada test

All patients completed comprehensive neuropsychological evaluations, including memory measures, as part of their standard pre-operative investigations. The adult patients (n=9) completed the Wechsler Memory Scale – Third Edition (3), and the one child in this study (P6) completed the Children’s Memory Scale (4). These memory measures produced indices of both immediate and delayed auditory/verbal and visual memory. These measures were scored and normed according to the respective test manuals resulting in standard scores with a mean of 100 and a standard deviation of 15.

For the Wada test, Brevital or Sodium Amobarbital wasinjected intothe petrous portion of the internal carotid artery. EEG was recorded to monitor the effect of Brevital/Sodium Amobarbital. Once hemiplegia contralateral to the side of the injection was demonstrated, four sets oftest cards (one set containing one picture, one object word, and one function word)were presented to the patient sequentially, allowing approximately five seconds per card. Motor strength was tested after eachcard set. Memory testing began afterfull recovery of motor strength and resolution of EEG slowing.

Surgical technique

Surgical techniques of electrode placement and post-operative care have been described in detail elsewhere (5). Briefly, subdural electrode arrays consisting of Platinum-Iridium electrodes measuring 3.97mm in diameter with acenter to center interelectrode distance of 10mm embedded in flexible silastic (custom made in house) were used to cover cerebral surface structures. Depth electrodes consisting of Platinum 2.5mm contacts with 10mm gap between contacts (Integra, Plainsboro NJ, USA) were used to target the mesial temporal and deeper gyral/sulcal regions. Electrode implantation and targeting of brain regions was tailored to recommendations made by a multidisciplinary patient management conference committee. Subdural electrodes ranged from 90 to 198 contacts (median 108) and depth electrodes ranged from 16-48 contacts (median 24) were implanted. Details of coverage for each patient are provided in Table 2. Following further discussion of all data together with the results of the ICEEG investigation, a standard anterior temporal lobectomy including removal of the mesial structures was performed in all patients.

Histopathology methods

Surgical specimens were submitted to the Department of Pathology for histopathological analysis. Microscopic slides were prepared from formalin-fixed, paraffin-embedded tissue, cut in thin sections (3-5m) and stained with hematoxylin-eosin. Pathological diagnosis of hippocampal sclerosis (6) was based on marked neuronal loss in the CA1 region (Sommer’s sector) and moderate loss in the CA3 and CA4 regions.

REFERENCE e-1

1. Wieser HG, ILAE Commission on Neurosurgery of Epilepsy. ILAE commission report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia 2004;45:695-714.

2. Luders H, Acharya J, Baumgartner C, et al. Semiological seizure classification. Epilepsia 1998;39:1006-1013.

3. Wechsler D. Wechsler Memory Scale (3rd ed). San Antonio, TX: The Psychological Corporation, 1997.

4. Cohen MJ. Children's Memory Scale. San Antonio: The Psychological Corporation, 1997.

5. Nair DR, Burgess R, McIntyre CC, Luders H. Chronic subdural electrodes in the management of epilepsy. Clin Neurophysiol 2008;119:11-28.

6. Sommer W. Erkrankung des Ammonshorns als aetiologisches Moment der Epilepsie. Arch Psychiatr Nervenkr 1880:631-675.