Malformations of Cortical Development Research Papers (original) (raw)
We describe the case of a 22-year-old male affected by NFLE reporting paroxysmal RLS-like symptoms. The patient was referred to our Sleep Center due to nocturnal paresthesias and cramps involving the left leg and leading to sleep... more
We describe the case of a 22-year-old male affected by NFLE reporting paroxysmal RLS-like symptoms. The patient was referred to our Sleep Center due to nocturnal paresthesias and cramps involving the left leg and leading to sleep fragmentation. At age 4, the patient presented with secondary generalized seizures preceded by left leg discomfort, controlled on CBZ. After successive therapy discontinuation, leg symptoms built up in frequency and duration until a secondary generalized seizure re-occurred. On CBZ prompt resumption no further GM seizures occurred albeit persistence of night-time frequent cramps and paraesthesia. Sleep EEG demonstrated asymmetric interictal sharp theta on the right posterior frontal areas, whereas brain MRI results were consistent with a Taylor type right frontal cortical dysplasia. CBZ augmentation and add on therapy with LEV led to further frequency reduction of sensory symptoms.
To determine clinical and EEG features that might help identify patients with epilepsy harboring small, intrinsically epileptogenic, surgically treatable, bottom-of-sulcus dysplasias (BOSDs). Retrospective review of clinical records, EEG,... more
To determine clinical and EEG features that might help identify patients with epilepsy harboring small, intrinsically epileptogenic, surgically treatable, bottom-of-sulcus dysplasias (BOSDs). Retrospective review of clinical records, EEG, MRI, and histopathology in 32 patients with drug-resistant epilepsy and MRI-positive (72% 3.0 tesla), pathologically proven (type 2B cortical dysplasia) BOSDs operated at our centers during 2005-2013. Localization of BOSDs was frontal in 19, insula in 5, parietal in 5, and temporal in 3, on the convexity or interhemispheric surfaces. BOSDs were missed on initial MRI at our centers in 22% of patients. Patients presented with focal seizures during infancy in 9, preschool years in 15, and school years in 8 (median age 5 years). Seizures were stereotyped, predominantly nocturnal, and typically nonconvulsive, with semiology referable to the fronto-central or perisylvian regions. Seizures occurred at high frequency during active periods, but often went i...
To define causative somatic mutations in resected brain tissue from an infant with intractable epilepsy secondary to hemispheric cortical dysplasia. Whole-exome sequencing was conducted on genomic DNA derived from both resected brain... more
To define causative somatic mutations in resected brain tissue from an infant with intractable epilepsy secondary to hemispheric cortical dysplasia. Whole-exome sequencing was conducted on genomic DNA derived from both resected brain tissue and peripheral blood leukocytes. Comparison of the brain vs blood sequencing results was performed using bioinformatic methods designed to detect low-frequency genetic variation between tissue pairs. Histopathology of the resected tissue showed dyslamination and dysmorphic neurons, but no balloon cells, consistent with focal cortical dysplasia type IIa. mTOR activation was observed by immunohistochemistry in the dysplasia. A missense mutation (c.4487T>G; p.W1456G) was detected in the FAT domain of MTOR in DNA from the dysplasia but not in lymphocytes. The mutation is predicted damaging (i.e., leading to mTOR activation) and was observed as a low-level mosaic with 8% of cells being heterozygous for the variant. We report the novel finding of an...
Gangliogliomas are a frequent cause of drug-resistant epilepsies in children. It remains unknown, however, whether gangliogliomas are intrinsically epileptogenic or if associated lesions contribute to their high epileptogenicity, ie... more
Gangliogliomas are a frequent cause of drug-resistant epilepsies in children. It remains unknown, however, whether gangliogliomas are intrinsically epileptogenic or if associated lesions contribute to their high epileptogenicity, ie associated focal cortical dysplasia (FCD ...
Cortical dysplasia (CD) has been classified as Taylor's focal... more
Cortical dysplasia (CD) has been classified as Taylor's focal cortical dysplasia (FCD type II) or other CD (FCD type I and mild malformation of cortical development) based on histological findings. The aims of this study were to determine whether MRI and magnetoencephalography (MEG) could distinguish between these two groups and to evaluate surgical outcomes. We evaluated the MRI features, MEG spike source (MEGSS) patterns (clusters or scatters) and postsurgical seizure outcomes of 27 children with CD. Thirteen patients had Taylor's FCD and 14 had other CD. MRI showed visible lesion in 22 (81%) patients. Tapering of abnormal white matter signals to the ventricles and cortical thickening were more prevalent in Taylor's FCD; focal hypoplasia and white matter atrophy were more prevalent in other CD. MEG showed spike sources in 26 (96%) patients. Taylor's FCD showed clustered MEGSSs in 6, both clustered and scattered MEGSSs in 5 and scattered MEGSSs in 2; other CD demonstrated clusters in 2, cluster and scatter in 10 and scatter in 1. Eleven (85%) of 13 patients who had complete resection of clustered MEGSSs achieved Engel class I outcome, but 4 (44%) of 9 patients with incomplete resections achieved class I. Fifteen (88%) of 17 patients who had complete resection of MRI lesions achieved class I, but 1 (33%) of 3 patients with incomplete lesionectomy was class I. There was no difference in surgical outcomes between Taylor's FCD and other CD. Surgical outcome was the same in both groups following complete removal of areas containing clustered MEGSSs and MR lesions.
Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop study, we showed that timing of AED withdrawal does not majorly influence long-term seizure... more
Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop study, we showed that timing of AED withdrawal does not majorly influence long-term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative IQ, and change in IQ (delta IQ) following pediatric epilepsy surgery. We collected IQscores of children from the TTS cohort with both pre- and postoperative neuropsychological assessments (NPA) (n=301) and analysed whether reduction of AEDs prior to the latest NPA was related to postoperative IQ and delta IQ, using linear regression analyses. Factors previously identified to independently relate to (delta) IQ, and currently identified predictors of (delta) IQ, were considered possible confounders and used for adjustment. Additionally, we adjusted for a compound propensity score that contained previously identified determinants of timing of AED withdrawal. Mean interval to...
High frequency oscillations (HFOs) called ripples (80-250 Hz) and fast ripples (FR, 250-500 Hz) can be recorded from intracerebral EEG macroelectrodes in patients with intractable epilepsy. HFOs occur predominantly in the seizure onset... more
High frequency oscillations (HFOs) called ripples (80-250 Hz) and fast ripples (FR, 250-500 Hz) can be recorded from intracerebral EEG macroelectrodes in patients with intractable epilepsy. HFOs occur predominantly in the seizure onset zone (SOZ) but their relationship to the underlying pathology is unknown. It was the aim of this study to investigate whether HFOs are specific to the SOZ or result from pathologically changed tissue, whether or not it is epileptogenic. Patients with different lesion types, namely mesial temporal atrophy (MTA), focal cortical dysplasia (FCD) and nodular heterotopias (NH) were investigated. Intracranial EEG was recorded from depth macroelectrodes with a sampling rate of 2000 Hz. Ripples (80-250 Hz) and Fast Ripples (250-500 Hz) were visually marked in 12 patients: five with MTA, four with FCD and three with NH. Rates of events were statistically compared in channels in four areas: lesional SOZ, non-lesional SOZ, lesional non-SOZ and non-lesional non-SOZ. HFO rates were clearly more linked to the SOZ than to the lesion. They were highest in areas in which lesion and SOZ overlap, but in patients with a SOZ outside the lesion, such as in NHs, HFO rates were clearly higher in the non-lesional SOZ than in the inactive lesions. No specific HFO pattern could be identified for the different lesion types. The findings suggest that HFOs represent a marker for SOZ areas independent of the underlying pathology and that pathologic tissue changes alone do not lead to high rates of HFOs.
Object Focal cortical dysplasia (FCD) represents a spectrum of developmental cortical abnormalities and is one of the most common causes of intractable epilepsy in children and young adults. Outcomes after surgery for FCD are highly... more
Object Focal cortical dysplasia (FCD) represents a spectrum of developmental cortical abnormalities and is one of the most common causes of intractable epilepsy in children and young adults. Outcomes after surgery for FCD are highly variable, and prognosticators of seizure freedom are unclear. In a subset of FCDs, a transmantle sign is observed on imaging that focally spans the entire cerebral mantle from the ventricle to the cortical surface. The aim of this study was to characterize seizure control outcomes and prognostic significance of the transmantle sign in FCD epilepsy. Methods Fourteen patients with the transmantle sign underwent epilepsy surgery for medically refractory epilepsy. Thirteen patients underwent resective surgery and 1 underwent multiple subpial transections with vagus nerve stimulator placement. Patient demographics, MRI, electroencephalography, intraoperative electrocorticography (ECoG), and pathology were reviewed. The results of this series were compared wit...