Different presurgical characteristics and seizure outcomes in children with focal cortical dysplasia type I or II.

PURPOSE: Cortical dysplasia (FCD) is a frequent cause of epilepsy in childhood. Two major pathological variants are distinguished, FCD type I and II. The aim of the study was to characterize differences between FCD type I and II with respect to imaging and EEG findings, clinical and neuropsychological presentations, and surgical outcome. METHODS: Forty children with refractory epilepsy and histopathologically confirmed FCD were retrospectively analyzed. FCD type I was identified in 24 and FCD type II in 16 patients. RESULTS: Characteristic MRI abnormalities in FCD type I included subtle white matter signal changes and regional reduction of the white matter volume. Typical MRI findings in FCD type II were increased cortical thickness, transmantle sign, gray-white matter junction blurring, fluid-attenuated inversion recovery (FLAIR) and proton density (PD) gray matter signal changes as well as T1w, and PD white matter signal changes. Continuous EEG slowing was significantly more common in patients with FCD type I. Children with FCD type I presented with lower levels of intelligence and were suffering more often from maladaptive behavior and behavioral disorders. Surgical outcome was significantly worse in the FCD type I group (seizure freedom was achieved in 21% FCD type I patients and in 75% FCD type II subjects, p < 0.001). CONCLUSIONS: Clinically important differences were found in children with distinct histopathological subtypes of FCD. Due to prominent neuropsychological deficits and worse seizure outcome, treatment strategies in FCD type I are more challenging than previously reported and these children should be recognized and specifically addressed within the incoherent group of patients with malformative brain disorders.

White matter angiopathy is common in pediatric patients with intractable focal epilepsies.

PURPOSE: The blood-brain barrier (BBB) and functional organization of blood vessels is severely affected in many epilepsy disorders. This was repetitively shown with respect to the cause, effect and treatment of seizures. In the present study, we investigated pathomorphological abnormalities of blood vessels in a cohort of young patients with chronic intractable seizures submitted to an epilepsy surgery program. METHODS: Histopathological examination was performed in surgical specimens obtained from 87 children with intractable epilepsies. Immunohistochemistry was employed to further characterize the basal membrane as well as specific cellular and tissue reactions. Pathological findings were correlated with clinical data including antiepileptic drug prescription. RESULTS: We identified an intriguing pattern of white matter angiopathy in 64.4% of our patient cohort. Major alterations included splitting of the basal membrane into endothelial and parenchymal leaves, which was restricted to arterioles and capillaries of the white matter and resulted in an extensively enlarged perivascular space. These cavities contained numerous blood cells and showed a spongiform appearance at the ultrastructural level. Angiopathic changes occurred independent from specific epilepsy-associated lesions, i.e., dysplasia, neoplasia, or hippocampal sclerosis, and showed no correlation with antiepileptic drug treatment or seizure semiologies. DISCUSSION: A high frequency of spongiform white matter angiopathy was identified in young patients with chronic epilepsies. The severity of basal membrane pathology and adjacent tissue reaction is compatible with compromised BBB function. Further clinicopathological investigations will be mandatory to clarify its relation to the cause or consequence of seizures in children with intractable seizures.

Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies.

Cortical dysplasias comprise a variable spectrum of clinical, neuroradiological and histopathological findings. We report about a cohort of 25 pediatric patients (mean age 8.1+/-4.8 years) with severe drug-resistant early onset focal epilepsies (mean duration 2.1+/-0.4 years), mental/psychomotor retardation, and multilobar epileptogenesis. Compared to age-matched biopsy controls, microscopical inspection of neurosurgically resected specimens revealed dysplastic neurons with/without balloon cells in only 7 patients. According to Palmini's classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II. All other patients presented with rather subtle but statistically significant neuroanatomical abnormalities. We identified increased numbers of ectopic neurons in white matter and cortical gliosis. However, most intriguing was our finding of a microcolumnar arrangement of cortical neurons in layer III. These microcolumns can be statistically defined as vertical lining of more than eight neurons (two times standard deviation of cell countings obtained from controls). In addition, neuronal perikarya were significantly smaller in epilepsy patients. Although histological abnormalities occurring during postnatal maturation of the brain challenge any neuropathological classification in this group of young patients, we propose that these findings are classified according to FCD type I. Our observations support a concept compatible with regional loss of high-order brain organization.