781 research outputs found
A developmental and genetic classification for malformations of cortical development: update 2012.
Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported. These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development
Focal cortical dysplasia: a practical guide for neurologists
Focal cortical dysplasia (FCD) is a malformation of cortical development characterised by disruption of cortical cytoarchitecture. Classification of FCDs subtypes has initially been based on correlation of the histopathology with relevant clinical, electroencephalographic and neuroimaging features. A recently proposed classification update recommends a multilayered, genotype-phenotype approach, integrating findings from histopathology, genetic analysis of resected tissue and presurgical MRI. FCDs are caused either by single somatic activating mutations in MTOR pathway genes or by double-hit inactivating mutations with a constitutional and a somatic loss-of-function mutation in repressors of the signalling pathway. Mild malformation with oligodendroglial hyperplasia in epilepsy is caused by somatic pathogenic SLC35A2 mutations. FCDs most often present with drug-resistant focal epilepsy or epileptic encephalopathy. Most patients respond to surgical treatment. The use of mechanistic target of rapamycin inhibitors may complement the surgical approach. Treatment approaches and outcomes have improved with advances in neuroimaging, neurophysiology and genetics, although predictors of treatment response have only been determined in part
Steps to Improve Precision Medicine in Epilepsy
Precision medicine is an old concept, but it is not widely applied across human health conditions as yet. Numerous attempts have been made to apply precision medicine in epilepsy, this has been based on a better understanding of aetiological mechanisms and deconstructing disease into multiple biological subsets. The scope of precision medicine is to provide effective strategies for treating individual patients with specific agent(s) that are likely to work best based on the causal biological make-up. We provide an overview of the main applications of precision medicine in epilepsy, including the current limitations and pitfalls, and propose potential strategies for implementation and to achieve a higher rate of success in patient care. Such strategies include establishing a definition of precision medicine and its outcomes; learning from past experiences, from failures and from other fields (e.g. oncology); using appropriate precision medicine strategies (e.g. drug repurposing versus traditional drug discovery process); and using adequate methods to assess efficacy (e.g. randomised controlled trials versus alternative trial designs). Although the progress of diagnostic techniques now allows comprehensive characterisation of each individual epilepsy condition from a molecular, biological, structural and clinical perspective, there remain challenges in the integration of individual data in clinical practice to achieve effective applications of precision medicine in this domain
Making memories: the development of long-term visual knowledge in children with visual agnosia
There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2 years and 3.7 years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment
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