Epilepsy surgery in the first months of life: a large type IIb focal cortical dysplasia causing neonatal drug-resistant epilepsy.

Focal cortical dysplasia is a common cause of medically refractory epilepsy in infancy and childhood. We report a neonate with seizures occurring within the first day of life. Continuous video-EEG monitoring led to detection of left motor seizures and a right frontal EEG seizure pattern. Brain MRI revealed a lesion within the right frontal lobe without contrast enhancement. The patient was referred for epilepsy surgery due to drug resistance to vitamin B6 and four antiepileptic drugs. Lesionectomy was performed at the age of two and a half months, and histopathological evaluation confirmed the diagnosis of focal cortical dysplasia type IIb (FCD IIb). The patient is free of unprovoked seizures without medication (Engel Class I) and is normally developed at 36 months after surgery. The case study demonstrates that FCD IIb may cause seizures within the first day of life and that epilepsy surgery can be successfully performed in medically intractable patients with a clearly identifiable seizure onset zone within the first three months of life. Although radical surgery such as hemispherectomy and multi-lobar resections are over-represented in early infancy, this case also illustrates a favourable outcome with a more limited resection in this age group.

Severe gyration and migration disorder in fetofetal transfusion syndrome: two case reports and a review of the literature on the neurological outcome of children with lesions on neuroimaging.

INTRODUCTION: Fetofetal transfusion syndrome is a dreaded cause of morbidity and mortality in monochorionic pregnancies. CASE REPORTS: We present two pairs of twins one of which we have followed for more than 6 years. The donors suffer from cerebral palsy, orofacial, and motor problems, and both are significantly smaller than their recipient twins. Interestingly, cranial MRI revealed medial frontal lobe polymicrogyria, ventriculomegaly, and decreased thickness in both parietal lobes in both donors. We suggest this as a possible feature of fetofetal transfusion syndrome. REVIEW: A minireview of the literature on neuroimaging and neurodevelopmental outcome in fetofetal transfusion syndrome is presented. CONCLUSION: While the close resemblance of the imaging features of both cases is likely incidental further study of a connection between migration and gyration disorders and fetofetal transfusion syndrome is warranted.

Pathologic Active mTOR Mutation in Brain Malformation with Intractable Epilepsy Leads to Cell-Autonomous Migration Delay.

The activation of phosphatidylinositol 3-kinase-AKTs-mammalian target of rapamycin cell signaling pathway leads to cell overgrowth and abnormal migration and results in various types of cortical malformations, such as hemimegalencephaly (HME), focal cortical dysplasia, and tuberous sclerosis complex. However, the pathomechanism underlying abnormal cell migration remains unknown. With the use of fetal mouse brain, we performed causative gene analysis of the resected brain tissues from a patient with HME and investigated the pathogenesis. We obtained a novel somatic mutation of the MTOR gene, having approximately 11% and 7% mutation frequency in the resected brain tissues. Moreover, we revealed that the MTOR mutation resulted in hyperphosphorylation of its downstream molecules, S6 and 4E-binding protein 1, and delayed cell migration on the radial glial fiber and did not affect other cells. We suspect cell-autonomous migration arrest on the radial glial foot by the active MTOR mutation and offer potential explanations for why this may lead to cortical malformations such as HME.

Clinical, imaging, and immunohistochemical characteristics of focal cortical dysplasia Type II extratemporal epilepsies in children: analyses of an institutional case series.

OBJECTIVE Focal cortical dysplasia (FCD) Type II is divided into 2 subgroups based on the absence (IIA) or presence (IIB) of balloon cells. In particular, extratemporal FCD Type IIA and IIB is not completely understood in terms of clinical, imaging, biological, and neuropathological differences. The aim of the authors was to analyze distinctions between these 2 formal entities and address clinical, MRI, and immunohistochemical features of extratemporal epilepsies in children. METHODS Cases formerly classified as Palmini FCD Type II nontemporal epilepsies were identified through the prospectively maintained epilepsy database at the British Columbia Children's Hospital in Vancouver, Canada. Clinical data, including age of seizure onset, age at surgery, seizure type(s) and frequency, affected brain region(s), intraoperative electrocorticographic findings, and outcome defined by Engel's classification were obtained for each patient. Preoperative and postoperative MRI results were reevaluated. H & E-stained tissue sections were reevaluated by using the 2011 International League Against Epilepsy classification system and additional immunostaining for standard cellular markers (neuronal nuclei, neurofilament, glial fibrillary acidic protein, CD68). Two additional established markers of pathology in epilepsy resection, namely, CD34 and α-B crystallin, were applied. RESULTS Seven nontemporal FCD Type IIA and 7 Type B cases were included. Patients with FCD Type IIA presented with an earlier age of epilepsy onset and slightly better Engel outcome. Radiology distinguished FCD Types IIA and IIB, in that Type IIB presented more frequently with characteristic cortical alterations. Nonphosphorylated neurofilament protein staining confirmed dysplastic cells in dyslaminated areas. The white-gray matter junction was focally blurred in patients with FCD Type IIB. α-B crystallin highlighted glial cells in the white matter and subpial layer with either of the 2 FCD Type II subtypes and balloon cells in patients with FCD Type IIB. α-B crystallin positivity proved to be a valuable tool for confirming the histological diagnosis of FCD Type IIB in specimens with rare balloon cells or difficult section orientation. Distinct nonendothelial cellular CD34 staining was found exclusively in tissue from patients with MRI-positive FCD Type IIB. CONCLUSIONS Extratemporal FCD Types IIA and IIB in the pediatric age group exhibited imaging and immunohistochemical characteristics; cellular immunoreactivity to CD34 emerged as an especially potential surrogate marker for lesional FCD Type IIB, providing additional evidence that FCD Types IIA and IIB might differ in their etiology and biology. Although the sample number in this study was small, the results further support the theory that postoperative outcome-defined by Engel's classification-is multifactorial and determined by not only histology but also the extent of the initial lesion, its location in eloquent areas, intraoperative electrocorticographic findings, and achieved resection grade.