Tom Pieper

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.

A Detailed Analysis of Frontal Lobe Seizure Semiology in Children Younger Than 7 Years

Summary:  Purpose: We sought to analyze semiology of seizure onset and evolution in young children with frontal lobe epilepsy (FLE), compare this with adult reports, and assess age‐related differences.

A distinct variant of focal cortical dysplasia type I characterised by magnetic resonance imaging and neuropathological examination in children with severe epilepsies.

Focal Cortical Dysplasias (FCDs) present with a large clinicopathological spectrum. FCDs are believed to relate directly to an epileptogenic condition, although seizure control by surgical resection is variable. This applies in particular to young children with multilobar FCDs, suffering from severe epilepsies and psychomotor retardation. Herein, we performed a comparative analysis of presurgically available data and microscopic inspection of resected cortical specimens to further characterise the pathomorphological spectrum of FCD. Multilobar resection procedures were performed in a consecutive series of 18 young children (mean 7.6 years) with severe pharmaco-resistant epilepsies following extensive presurgical surface-/invasive video-EEG monitoring intraoperative electro-corticography (iECoG), as well as high resolution MRI. In all cases, systematic neuropathological examination of surgical specimens was performed with respect to architectural abnormalities and cell density measurements. These histomorphological data were compared with volumetric MRI analysis. Histopathological examination revealed increased neuronal densities correlating with decreased cortical thickness and abundance of neuronal microcolumns in all cases. Intriguingly, the affected cerebral hemisphere was significantly smaller, relative to the non-epileptogenic contralateral side, in 16 children of our patient series. In conclusion, hypoplastic neocortex and columnar architectural disorganisation point to compromised cortical development, and appear as distinct FCD I subtype in children suffering from severe epilepsies and psychomotor retardation.

Efficacy and safety of radiosurgical callosotomy: a retrospective analysis.

Summary:  Purpose: Anterior callosotomy is a surgical option for the treatment of generalized tonic or atonic seizures associated with drop attacks. Besides open surgery, a radiosurgical callosal disconnection using the gamma knife (GK) also can be performed, but reliable data about tolerability and efficacy are sparse.

Co-occurring malformations of cortical development and SCN1A gene mutations

To report on six patients with SCN1A mutations and malformations of cortical development (MCDs) and describe their clinical course, genetic findings, and electrographic, imaging, and neuropathologic features.

Clinical functional MRI of the language domain in children with epilepsy

Functional MRI (fMRI) for the assessment of language functions is increasingly used in the diagnostic workup of patients with epilepsy. Termed “clinical fMRI,” such an approach is also feasible in children who may display specific patterns of language reorganization. This study was aimed at assessing language reorganization in pediatric epilepsy patients, using fMRI. We studied 26 pediatric epilepsy patients (median age, 13.05 years; range, 5.6–18.7 years) and 23 healthy control children (median age, 9.37 years; range, 6.2–15.4 years), using two child‐friendly fMRI tasks and adapted data‐processing streams. Overall, 81 functional series could be analyzed. Reorganization seemed to occur primarily in homotopic regions in the contralateral hemisphere, but lateralization in the frontal as well as in the temporal lobes was significantly different between patients and controls. The likelihood to find atypical language organization was significantly higher in patients. Additionally, we found significantly stronger activation in the healthy controls in a primarily passive task, suggesting a systematic confounding influence of antiepileptic medication. The presence of a focal cortical dysplasia was significantly associated with atypical language lateralization. We conclude that important confounds need to be considered and that the pattern of language reorganization may be distinct from the patterns seen in later‐onset epilepsy. Hum Brain Mapp, 2011.

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.

Predicting hand function after hemispherotomy: TMS versus fMRI in hemispheric polymicrogyria.

Patients with hemispheric malformations of cortical development (such as polymicrogyria) often develop medically intractable epilepsies for which hemispherotomy can be an excellent treatment option. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are noninvasive methods used to evaluate the sensorimotor system in adults and children before surgery. Preoperative results of both methods and their predictive values regarding hand function after hemispherotomy are described in four boys with hemispheric polymicrogyria, pharmacoresistent epilepsy, and hemiparesis with preserved grasp function of the paretic hand. TMS showing ipsilateral projections from the contralesional hemisphere but no evidence of crossed corticospinal projections from the lesioned hemisphere correctly predicted preserved postoperative grasp function in all four patients. In contrast, the interpretation of sensorimotor fMRI in patients with congenital hemiparesis is more difficult, as ipsilesional activation can occur as it was the case in three of four patients in the current study. This activation might represent contralaterally preserved primary somatosensory (S1) and not primary motor (M1) representation and is apparently not necessary for the paretic hand to still perform grasp movements.

Why one task is not enough: Functional MRI for atypical language organization in two children

Functional MRI is increasingly used to determine the hemispheric dominance for language. This is especially relevant in children who may not be able to comply with the high demands of a Wada test. We here report on two children in which the full extent of language reorganization was only determined when two fMRI tasks were analyzed; in the first case, the results from the second task corroborated the shifted hemispheric dominance seen in the first task. In the second case, the second task showed an opposite hemispheric dominance, suggesting a hemispheric dissociation of language functions. These cases underline the necessity to use more than one fMRI task for the determination of hemispheric dominance, whenever possible. This is particularly relevant in children as unusual patterns of reorganization may be more likely.

Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Frontal Lobe Epilepsy: A New Clinico-Pathological Entity.

The histopathological spectrum of human epileptogenic brain lesions is widespread including common and rare variants of cortical malformations. However, 2–26% of epilepsy surgery specimens are histopathologically classified as nonlesional. We hypothesized that these specimens include also new diagnostic entities, in particular when presurgical magnetic resonance imaging (MRI) can identify abnormal signal intensities within the anatomical region of seizure onset. In our series of 1381 en bloc resected epilepsy surgery brain specimens, 52 cases could not be histopathologically classified and were considered nonlesional (3.7%). An increase of Olig2‐, and PDGFR‐alpha‐immunoreactive oligodendroglia was observed in white matter and deep cortical layers in 22 of these patients (42%). Increased proliferation activity as well as heterotopic neurons in white matter were additional histopathological hallmarks. All patients suffered from frontal lobe epilepsy (FLE) with a median age of epilepsy onset at 4 years and 16 years at epilepsy surgery. Presurgical MRI suggested focal cortical dysplasia (FCD) in all patients. We suggest to classify this characteristic histopathology pattern as “mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE).” Further insights into pathomechanisms of MOGHE may help to bridge the diagnostic gap in children and young adults with difficult‐to‐treat FLE.