Areas Of Focal Cortical Dysplasia Research Articles

Surgical Resection of Focal Cortical Dysplasia in a Neonate with Novel TSC1 Mutation Leading to Resolution of Refractory Seizures: Case Report

We describe a neonate presenting on first day of life with refractory seizures secondary to a single, large area of focal cortical dysplasia (FCD) who underwent surgical resection at age 3 weeks leading to resolution of seizure activity and dramatic improvement in developmental trajectory. Surgical intervention for epilepsy is infrequently offered for neonates, often reserved only for those with catastrophic presentations. This case demonstrates that surgical intervention can be safe and efficacious in neonates for pharmaco-resistant seizures associated with a focal lesion. Rapid whole exome sequencing in this case yielded a germline novel de novo TSC1 mutation, leading to a genetic diagnosis of tuberous sclerosis complex (TSC). Our patient demonstrates an atypical neonatal presentation of TSC. Limited data is available for those with isolated FCD in TSC; this is the first reported case in a neonate.

Perfusion Imaging of Focal Cortical Dysplasia Using Arterial Spin Labeling

Focal cortical dysplasia is the most common malformation of cortical development, causing intractable epilepsy. This study investigated the relationship between brain perfusion and microvessel density in 7 children with focal cortical dysplasia. The authors analyzed brain perfusion measurements obtained by magnetic resonance imaging of 2 of the children and the microvessel density of brain tissue specimens obtained by epilepsy surgery on all of the children. Brain perfusion was approximately 2 times higher in the area of focal cortical dysplasia compared to the contralateral side. The microvessel density was nearly double in the area of focal cortical dysplasia compared to the surrounding cortex that did not have morphological abnormalities. These findings suggest that hyperperfusion can be related to increased microvessel density in focal cortical dysplasia rather than only to seizures. Further investigations are needed to determine the relationship between brain perfusion, microvessel density, and seizure activity.

Multi-focal occurrence of cortical dysplasia in epilepsy patients

This study describes the existence and the clinical and electrophysiological features of multi-focal cortical dysplasia in epilepsy patients. Five patients with intractable focal epilepsy are reported. All patients underwent invasive presurgical video-electroencephalography monitoring. Localization of dysplastic areas was based on high-resolution magnetic resonance scanning, surface and intracranial electroencephalography. Four patients underwent epilepsy surgery. Histological findings in focal cortical dysplasia (FCD) were classified according to Palmini. In addition, genetic examinations were performed in order to assess possible mutations in the genes for tuberous sclerosis complex. In four patients, FCDs were located in the same hemisphere. One case presented with bilateral FCDs. In three patients seizures arose from two separate dysplastic areas and in one patient, one lesion showed only interictal activity. In one further patient, seizures started exclusively from the hippocampus. In two of three patients with removal of the FCDs, the histological subtype was identical (Palmini type 2) and in one patient, histology differed between the lesions. All operated patients became seizure-free. In patients with FCD type 2, germ-line mutations in the tuberous sclerosis complex genes were not detectable. Dysplastic brain regions may not be restricted to a single brain region. Areas of FCD can have different degrees of epileptogenicity, ranging from electrographic silence to interictal epileptic discharges and initial involvement in seizure generation. Based on genetic analysis and clinical features, multi-FCD in this patient series was not likely to be related to tuberous sclerosis.

Spatially filtered magnetoencephalography compared with electrocorticography to identify intrinsically epileptogenic focal cortical dysplasia

This study was carried out to evaluate Synthetic Aperture Magnetometry-kurtosis (SAM(g(2))), a spatially filtered source localization technique in magnetoencephalography (MEG), for identification of epileptogenic areas of focal cortical dysplasia (FCD). Three children with FCD were investigated to localize the ictal onset zone (IOZ). All patients subsequently had extraoperative electrocorticography (ECoG) for intractable epilepsy and surgical resection. SAM(g(2)) analysis showed overlapping of interictal MEG spike sources with the IOZ on ECoG in all children. We recommend MEG-SAM(g(2)) and MEG interictal spike source localization in patients with epileptogenic FCD.

Disturbance of Notch-1 and Wnt signalling proteins in neuroglial balloon cells and abnormal large neurons in focal cortical dysplasia in human cortex.

Determination of neuroglial cell fate and neural tube development during embryogenesis is influenced by the Notch/Wnt signalling pathway. We have studied the localisation of several proteins in the Wnt pathway in focal cortical dysplasia (FCD). This disorder, thought to be due to abnormalities of neuronal migration and differentiation, contains regions of morphologically normal neocortex interrupted by areas of neuronal laminar disorganisation, heterotopic white matter neurons, abnormal large neurons and balloon cells of uncertain histogenesis. We found that the subcellular distribution of several proteins involved in the Wnt pathway differed in regions of FCD from normal cortex, and that within the areas of FCD, the pattern varied with cellular phenotype. Thus, in balloon cells, elevated cytoplasmic levels of dishevelled (Dvl-1) protein were accompanied by an absence of Notch-1, increased adenomatous poliposis coli (APC), altered cytoplasmic beta-catenin, and reduced nuclear expression of beta-catenin. A contrasting pattern of expression was found in abnormal large neurons, which demonstrated elevated levels of Notch-1, and glycogen synthase kinase-3beta (GSK-3beta), and normal levels of APC. Our results are consistent with the notion that Wnt/Notch signalling influences neuroglial cell fate, and suggest that a perturbation of Wnt/Notch signalling may contribute to the neuropathology of FCD.

Cognitive deterioration associated with focal cortical dysplasia

Surgery for an area of focal cortical dysplasia in a critical region is reported in a right-handed female manifesting intractable focal epilepsy and verbal cognitive deterioration. She developed the first seizure at 2 years of age and was treated with phenytoin and zonisamide, with good control until 10 years of age. Although seizures did not occur at 9 years of age, she manifested dyscalculia, right-left disorientation, and finger agnosia, and N-isopropyl- p -iodoamphetamine single-photon emission computed tomography (SPECT) revealed focal hypoperfusion in the left parietal lobe. At 11 years of age, she developed regular nocturnal seizures and gradually lost the ability to understand the meaning of sentences. Verbal IQ declined from 94 to 63, and the area of hypoperfusion detected by interictal N-isopropyl- p -iodoamphetamine SPECT spread over the left parietotemporal lobes. Magnetic resonance imaging revealed focal cortical dysplasia mainly in the left parietal lobe, and ictal technetium-99m-ethyl cysteinate dimer SPECT images demonstrated an area of hyperperfusion around the focal cortical dysplasia, including the left precentral gyrus. Because of the overlap between the epileptogenic and functional cortex, the authors concluded that cortical resection, including focal cortical dysplasia, was inappropriate in this patient.

Lipomas of the frontal lobe

An extremely rare case of lipomas on the cerebral surface in a 65-year-old female is reported. The tumors were located both in an unusual fissure of the right frontal convexity and under the right frontal lobe associated with and surrounded by areas of focal cortical dysplasia. Angiograms revealed dilated branches of the right anterior cerebral artery associated with angiomatous tumor blushes. The etiology of the combination of the lipomas and the anomalies, and the angiographic features, are briefly discussed.

Orbitofrontal resections for intractable partial seizures

The orbitofrontal cortex has extensive connections with limbic structures that are often involved in intractable partial seizures. Although some cases of orbitofrontal epilepsy have been reported, the exact incidence and optimal means of diagnosis and treatment of this condition are not well established. For 1 year, we included recordings from the orbitofrontal cortex in all cases of limbic epilepsy that required invasive monitoring as part of a preoperative workup. We identified 3 cases in which orbitofrontal resections were performed to control intractable partial seizures. In 1 case, an orbitofrontal resection based on physiologic data disclosed an area of focal cortical dysplasia that had not been identified by preoperative structural and functional imaging. In the second case, the adjacent orbitofrontal area was resected concurrently with a dominant anterior temporal lobectomy (ATL). In the third case, a patient was seizure-free for 6 years after an ATL. The seizures recurred, however, and an orbitofrontal resection was performed on the same side as the original surgery. These patients had no unique EEG or semiology profile that identified orbitofrontal seizures before invasive recordings were made. The orbitofrontal cortex may be the source of intractable partial seizures, and this should be considered in electrode implantation strategies for the preoperative evaluation of patients with this disorder.