Barbara Schmeiser

Extent of mossy fiber sprouting in patients with mesiotemporal lobe epilepsy correlates with neuronal cell loss and granule cell dispersion.

OBJECTIVE The most frequent finding in temporal lobe epilepsy is hippocampal sclerosis, characterized by selective cell loss of hippocampal subregions CA1 and CA4 as well as mossy fiber sprouting (MFS) towards the supragranular region and granule cell dispersion. Although selective cell loss is well described, its impact on mossy fiber sprouting and granule cell dispersion remains unclear. MATERIALS AND METHODS In a single center series, we examined 319 human hippocampal specimens, collected in a 15-years period. Hippocampal specimens were stained for neuronal loss, granule cell dispersion (Wyler scale I-IV, Neu-N, HE) and mossy fiber sprouting (synaptoporin-immunohistochemistry). For seizure outcome Engel score I-IV was applied. RESULTS In Wyler I and II specimens, mossy fibers were found along their natural projection exclusively in CA4 and CA3. In Wyler III and IV, sprouting of mossy fibers into the molecular layer and a decrease of mossy fibers in CA4 and CA3 was detected. Mean granule cell dispersion was extended from 121μm to 185μm and correlated with Wyler III-IV as well as mossy fiber sprouting into the molecular layer. Wyler grade, mossy fiber sprouting and granule cell dispersion correlated with longer epilepsy duration, late surgery and higher preoperative seizure frequency. Parameters analyzed above did not correlate with postoperative seizure outcome. DISCUSSION Mossy fiber sprouting might be a compensatory phenomenon of cell death of the target neurons in CA4 and CA3 in Wyler III-IV. Axonal reorganization of granule cells is accompanied by their migration and is correlated with the severity of cell loss and epilepsy duration.

Long-term outcome characteristics in mesial temporal lobe epilepsy with and without associated cortical dysplasia

OBJECT The intention of our study was to identify predictive characteristics for long-term seizure control and running down phenomenon after surgical treatment of pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated cortical dysplasia. MATERIALS AND METHODS Our study comprises a consecutive series of 458 patients who underwent surgical treatment for intractable mTLE at the Epilepsy Center Freiburg. Data evaluated included semiology, duration and frequency of seizures, results of presurgical diagnostics including video-EEG monitoring, MRI, PET and SPECT as well as postoperative seizure outcome. Results were evaluated forming two groups: Group A consisted of isolated mesiotemporal lesions. Group B comprised patients with mTLE and additional focal cortical dysplasia (FCD). Statistical evaluation was based on the Kaplan Meier survival analysis, using log-rank-tests and a multivariate regression model. Postoperative running down phenomenon was defined as seizure freedom after a period of gradual reduction of postoperative seizure frequency. This was compared to patients with ongoing epilepsy. RESULTS Complete seizure freedom was achieved in 65.0% of investigated patients at 1year and in 56.5% at long-term follow-up of ≥5 years after surgery. Corresponding results were 64.2% and 56.8% at 1 and ≥5 years, respectively in group A and 66.4% and 56.0%, respectively in group B. Predictive for favorable postoperative outcome in the total group were younger age at surgery, shorter duration of epilepsy, absence of secondarily generalized tonic-clonic seizures (SGTCS), presence of strictly ipsilateral temporal interictal epileptiform discharges (IEDs), complete resection of the lesion as well as absence of postoperative epileptiform activity and of early postoperative seizures. In subgroup analyses, patients of group A demonstrated longer postoperative seizure-free intervals with adolescent age at surgery, short duration of epilepsy before surgery and absence of SGTCS, whereas in patients of group B ipsilateral temporal seizure onset and strictly unilateral IEDs in EEG as well as complete resection were predictors for favorable seizure outcome. Furthermore, absence of early postoperative seizures and of spikes in EEG were predictive factors for long-term seizure-freedom in both subgroups. The running down phenomenon was found in 33 (7.2%) patients. None of the parameters evaluated demonstrated significant predictive power. Only late seizure onset and neoplastic lesions showed a trend for postoperative gradual seizure reduction in multivariate analyses. CONCLUSION Depending on the presence or absence of focal cortical dysplasia in addition to mesiotemporal structural alterations, predictors of long-term seizure control differed regarding the relevant clinical and electrophysiological features. This is important for specific patient counseling in respective groups.

Surgical Treatment of Mesiotemporal Lobe Epilepsy: Which Approach is Favorable?

BACKGROUND Mesiotemporal lobe epilepsy is one of the most frequent causes for pharmacoresistant epilepsy. Different surgical approaches to the mesiotemporal area are used. OBJECTIVE To analyze epileptological and neuropsychological results as well as complications of different surgical strategies. METHODS This retrospective study is based on a consecutive series of 458 patients all harboring pharmacoresistant mesiotemporal lobe epilepsy. Following procedures were performed: standard anterior temporal lobectomy, anterior temporal or key-hole resection, extended lesionectomy, and transsylvian and subtemporal selective amygdalohippocampectomy. Postoperative outcome was evaluated according to different surgical procedures. RESULTS Overall, 1 yr after surgery 315 of 432 patients (72.9%) were classified Engel I; in particular, 72.8% were seizure-free after anterior temporal lobectomy, 76.9% after key-hole resection, 84.4% after extended lesionectomy, 70.3% after transylvian selective amygdalohippocampectomy, and 59.1% after subtemporal selective amygdalohippocampectomy. No significant differences in seizure outcome were found between different resective procedures, neither in short-term nor long-term follow-up. There was no perioperative mortality. Permanent morbidity was encountered in 4.4%. There were no significant differences in complications between different resection types. In the majority of patients, selective attention improved following surgery. Patients after left-sided operations performed significantly worse regarding verbal memory as compared to right-sided procedures. However, surgical approach had no significant effect on memory outcome. CONCLUSION Different surgical approaches for mesiotemporal epilepsy analyzed resulted in similar epileptological, neuropsychological results, and complication rates. Therefore, the approach for the individual patient does not only depend on the specific localization of the epileptogenic area, but also on the experience of the surgeon.

Different mossy fiber sprouting patterns in ILAE hippocampal sclerosis types

OBJECTIVE Hippocampal sclerosis (HS) is the most prevalent pathology in temporal lobe epilepsy (TLE) characterized by segmental neuronal cell loss in the cornu ammonis (CA) 1-4. In addition, migration of granule cells and reorganization of their axons is observed, known as granule cell dispersion (GCD) and mossy fiber sprouting (MFS). The loss of mossy fibers` (MF) target cells in CA4 and CA3 was considered to be causative for MFS. The ILAE HS (International League Against Epilepsy) classification identifies three subtypes with different cell loss patterns in CA1-4. We studied the relation of ILAE HS subtypes to GCD and MFS to corroborate clinico-pathological subgroups in a large retrospective single-center series. MATERIAL AND METHODS Hippocampal specimen of 319 patients were screened, 214 could be used for analysis. Immunohistochemical stainings for semi-quantitative analysis of neuronal cell loss (NeuN) and MFS (synaptoporin) were performed. Presurgical data were available from patient files and seizure outcome was classified according to Engel score after surgery. RESULTS In 39 patients (18%) no neuronal cell loss (ILAE no-HS), no GCD and no MFS was observed. In 154 patients (72%) severe neuronal cell loss was seen in CA1, CA4 and CA3 (ILAE HS 1, typical HS); in addition extensive GCD and MFS was observed. In 17 patients (8%) cell loss was seen predominantly in CA1 (ILAE HS 2); despite different cell loss pattern these hippocampi also showed GCD and MFS. In 4 patients (2%) cell loss was predominately detected in CA3 and CA4 (ILAE HS type 3), consecutively GCD and MFS were observed. Longer epilepsy duration and younger age at surgery was more often associated with ILAE HS 2 and febrile convulsions were completely absent in ILAE no-HS. Yet, seizure onset, age at initial precipitating injury and postsurgical seizure outcome did not show any significant association with ILAE HS subtypes. CONCLUSION GCD and MFS might develop independently from the neuronal cell loss of MF target cells.

Functional hemispherectomy is safe and effective in adult patients with epilepsy

INTRODUCTION Functional hemispherectomy (FH) is a well-established therapeutic option for children with epilepsy with parenchymal damage confined to one hemisphere, yet its application in adults remains rare. The intention of our study was to investigate postoperative clinical and epileptological outcome in adults who received FH for intractable epilepsy. MATERIALS AND METHODS We retrospectively analyzed 12 adult patients (18-56years) with intractable epilepsy due to unihemispheric pathology. All patients underwent FH. Postoperative neurological and cognitive outcome as well as seizure status were evaluated with a mean follow-up period of 4.9years. RESULTS Ten patients (83%) were seizure-free (Engel I), and two (17%) had recurrent seizures at last follow-up. Apart from one patient requiring operative revision for bone flap infection, no perioperative morbidity or mortality occurred. Postoperative functional assessment revealed deterioration of motor function in 7 patients, whereas 5 remained unchanged. Language was unchanged in 8 patients. The absence of background slowing in preoperative electroencephalogram (EEG) as well as ictal and interictal EEG patterns located ipsilateral to the side of surgery was associated with favorable seizure outcome. CONCLUSION Favorable seizure control and acceptable functional outcome can be achieved by FH in adults with intractable epilepsy. The risk of postoperative deficits is moderate and even older patients are able to manage postoperative motor impairment. Therefore, FH should be considered in case of unihemispheric lesions also in adults.

Bilateral cingulum fiber reductions in temporal lobe epilepsy with unilateral hippocampal sclerosis

PURPOSE To evaluate whether white matter tracts within the Papez circuit are altered in patients with unilateral hippocampal sclerosis (HS). METHODS Twenty patients with histologically proven unilateral HS and 20 age-matched controls were studied with a 3T Epilepsy-dedicated MRI protocol including a MPRAGE sequence for hippocampus volumetry and a diffusion tensor imaging (DTI) sequence (61 diffusion-encoding directions, 2×2×2mm3 voxels) for diffusion tensor tractography (DTT). An energy-based global tracking algorithm was used to calculate streamline counts (SC) and fractional anisotropy (FA) of cingulate, fornix, and mammillo-thalamic tracts, respectively. RESULTS Sclerotic hippocampi were significantly smaller compared to the contralateral side and to age-matched controls. Cingulum SC but not FA were reduced on the hippocampal sclerosis (258+81.0) and contralateral side (271+85.6) compared to age-matched controls (447+138). CONCLUSION Focusing on white matter tracts of the Papez circuit we showed that in patients with intractable temporal lobe epilepsy unilateral hippocampal sclerosis is associated with a bilateral reduction of cingulum association fibers projecting from the cingulate gyrus to the parahippocampal gyrus.

Visual field defects following different resective procedures for mesiotemporal lobe epilepsy

INTRODUCTION One of the most common side effects of mesiotemporal lobe resection in patients with medically intractable epilepsy are visual field defects (VFD). While peripheral defects usually remain unnoticed by patients, extended VFD influence daily life activities and can, in particular, affect driving regulations. This study had been designed to evaluate frequency and extent of VFD following different surgical approaches to the mesiotemporal area with respect to the ability to drive. MATERIALS AND METHODS This study comprises a consecutive series of 366 patients operated at the Epilepsy Center in Freiburg for intractable mesiotemporal lobe epilepsy from 1998 to 2016. The following procedures were performed: standard anterior temporal lobectomy (ATL: n=134; 37%), anterior temporal or keyhole resection (KH: n=53; 15%), and selective amygdalohippocampectomy via the transsylvian (tsAHE: n=145; 40%) and the subtemporal (ssAHE: n=34; 9%) approach. Frequency and extent of postoperative VFD were evaluated in relation to different surgical procedures. According to the German driving guidelines, postoperative VFD were classified as driving-relevant VFD with the involvement of absolute, homonymous central scotoma within 20° and driving-irrelevant VFD with either none or exclusively minor VFD sparing the center. RESULTS Postoperative visual field examinations were available in 276 of 366 cases. Postoperative VFD were observed in 202 of 276 patients (73%) and were found to be driving-relevant in 133 of 276 patients (48%), whereas 69 patients (25%) showed VFD irrelevant for driving. Visual field defects were significantly less likely following ssAHE compared with other temporal resections, and if present, they were less frequently driving-relevant (p<0.05), irrespective of the side of surgery. CONCLUSION Subtemporal sAHE (ssAHE) caused significantly less frequently and less severely driving-relevant VFD compared with all other approaches to the temporal lobe, irrespective of the side of surgery.