Focal cortical dysplasia

Focal cortical dysplasia (FCD) is a developmental disorder of the cerebral cortex and a main cause of drug-resistant epilepsy in children. A loss of the excitation and inhibition (E/I) balance has emerged as a key feature for neuronal hyperexcitability, underlying the pathogenesis of seizures. However, it remains unclear how synaptic ultrastructure is altered in the human patients with FCD. Here we performed morphological analyses on the synaptic density, shape, and distribution of intrasynaptic organelles in the temporal cortical layer III of a FCD patient using 3D electron microscopy. Our qu

…in a spectrum of defects ranging from focal cortical dysplasia to hemimegalencephaly (HME). HME is a rare disorder, characterized by the enlargement of one hemisphere. To date, a detailed cellular and molecular understanding of the neuropathological und

Focal cortical dysplasia (FCD) is a regional malformation of cortical development frequently associated with pharmacoresistant epilepsy. It is caused by somatic mutations affecting the mTOR signaling pathway within excitatory neurons. At the cellular level, FCD manifests as the emergence of dysmorphic neurons, disrupted neuronal migration, and consequent alterations in neuronal circuitry, accompanied by seizure occurrence. It has been demonstrated that physiological neuronal activity stimulates oligodendrocyte lineage cells (OLCs) to proliferate, differentiate, and myelinate. We hypothesize th

…a patient with epilepsy, caused by focal cortical dysplasia. The recordings revealed frequency-dependent suppression of neocortical interictal discharges linked to the application of CMS. There was no change in neocortical interictal discharges with 50Hz CMS, but with CMS at 70Hz, 100Hz and 150Hz, varying periods of suppression were observed during and/or after stimulation. We

Epilepsy surgery is a safe but underutilised treatment for drug-resistant focal epilepsy. One challenge in the presurgical evaluation of patients with drug-resistant epilepsy are patients considered “MRI negative”, i.e. where a structural brain abnormality has not been identified on MRI. A major pathology in “MRI negative” patients is focal cortical dysplasia (FCD), where lesions are often small or subtle and easily missed by visual inspection. In recent years, there has been an explosion in artificial intelligence (AI) research in the field of healthcare. Automated FCD detection is an area wh

Epilepsy is one of the most common neurological diseases according to the World Health Organization (WHO) affecting around 70 million people worldwide [WHO]. Patients who suffer from epilepsy also suffer from a variety of neuro-psychiatric co-morbidities, which they can experience as crippling as the seizure condition itself. Adequate organization of cerebral white matter is utterly important for cognitive development. The failure of integration of neurologic function with cognition is reflected in neuro-psychiatric disease, such as autism spectrum disorder (ASD). However, in epilepsy we know

Focal Cortical Dysplasia (FCD) is the most common focal cortical malformation leading to intractable childhood focal epilepsy. In recent years, we and others have shown that FCD type II is caused by mosaic mutations in genes within the PI3K-AKT-mTOR-signaling pathway. Hyperactivation of the mTOR pathway accounts for neuropathological abnormalities and seizure occurrence in FCD. We further showed from human surgical FCDII tissue that epileptiform activity correlates with the density of mutated dysmorphic neurons, supporting their pro-epileptogenic role. The level of mosaicism, as defined by var

Epilepsy is one of the most common neurological diseases according to the World Health Organization (WHO) affecting around 70 million people worldwide [WHO]. Patients who suffer from epilepsy also suffer from a variety of neuro-psychiatric co-morbidities, which they can experience as crippling as the seizure condition itself. Adequate organization of cerebral white matter is utterly important for cognitive development. The failure of integration of neurologic function with cognition is reflected in neuro-psychiatric disease, such as autism spectrum disorder (ASD). However, in epilepsy we know

Tuberous sclerosis complex (TSC) and focal cortical dysplasia type II (FCDII) are caused by mutations in mTOR pathway genes leading to mTOR hyperactivity, focal malformations of cortical development (fMCD), and seizures in 80-90% of the patients. The current definitive treatments for epilepsy are surgical resection or treatment with everolimus, which inhibits mTOR activity (only approved for TSC). Because both options have severe limitations, there is a major need to better understand the mechanisms leading to seizures to improve life-long epilepsy treatment in TSC and FCDII. To investigate su