Fresh specimens of human and rat neocortex were used to determine direct and indirect inhibitory potencies of choline esterase inhibitors (ChEIs) on ChE and the release of acetylcholine (ACh), respectively. Km values of ChE in homogenates of rat and
Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy.We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%).The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients.In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).
The new International League Against Epilepsy (ILAE) classification for focal cortical dysplasia (FCD) differentiates between patients with isolated FCD (type 1) and FCD with an associated hippocampal sclerosis (HS) (type 3a). In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis. We investigated in a cohort of 100 patients with exclusively temporal FCD if the new subdivision of FCD is reflected in clinical characteristics.Thirty-one patients with FCD type 1 and 50 patients with FCD type 3a in the temporal lobe were included. In all patients MRI and histology of the FCD were available. Both patient groups were compared to 19 patients with temporal FCD type 2 with clearly different histologic appearance.Patients with FCD type 1 and type 3a presented with similar clinical features in many respects. In univariate analyses, no statistically significant differences were found as to age at epilepsy onset (p = 0.07) and epilepsy surgery (p = 0.14), a normal appearing neocortical temporal lobe (p = 0.08) or diagnosis of FCD by visual inspection of MRI (p = 0.08), preoperative seizure frequency (p = 0.06), and the predominance of an epigastric aura (p = 0.08). The postoperative outcome was nearly identical 1 year (p = 0.8) and 2 (p = 0.8), 3 (p = 0.8), 5 (p = 0.7), and 8 (p = 1.0) years postoperatively. Only febrile seizures (p = 0.025) and an aura (p = 0.03) were significantly more frequently reported in patients with FCD type 3a. Similar results were obtained from a multivariate logistic regression analysis. Patients with FCD type 2 were more different: Compared to FCD type 3a, age at epilepsy surgery was significantly lower (p = 0.004) and auras (p = 0.005) were significantly less frequently reported. Epigastric auras (p = 0.04) and febrile seizures (p = 0.025) occurred significantly less frequently in patients with FCD type 2 without HS compared to FCD type 3a. The diagnosis of an FCD was significantly more frequently made (p = 0.03) by visual inspection of the MRI compared to FCD type 1.Clinical features did not allow to clear separation of temporal FCD types 1 and 3a. Statistically significant differences were seen in a history of febrile seizures and the occurrence of auras more common in FCD type 3a. However, FCD type 2 in the same localization but with different histology presented with further differences such as more frequent FCD diagnosis by visual inspection of MRI, earlier operation, and less frequent epigastric auras.