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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The malformations of the cerebral cortex represent a major cause of developmental disabilities, severe epilepsy and reproductive disadvantage. The advent of high-resolution MRI techniques has facilitated the in vivo identification of a large group of cortical malformation phenotypes. Several malformation syndromes caused by abnormal cortical development have been recognised and specific causative gene defects have been identified. Periventricular nodular heterotopia (PNH) is a malformation of neuronal migration in which a subset of neurons fails to migrate into the developing cerebral cortex. X-linked PNH is mainly seen in females and is often associated with focal epilepsy. FLNA mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of PNH due ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay and early seizures. Lissencephaly-pachygyria and subcortical band heterotopia (SBH) are disorders of neuronal migration and represent a malformative spectrum resulting from mutations of either LIS1 or DCX genes. LIS1 mutations cause a more severe malformation in the posterior brain regions. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior SBH owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in males and SBH in female patients. Mutations of DCX have also been found in male patients with anterior SBH and in female relatives with normal brain magnetic resonance imaging. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin (RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and seizures with suppression-burst EEG. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene. Epilepsy is often present in patients with cortical malformations and tends to be severe, although its incidence and type vary in different malformations. It is estimated that up to 40% of children with drug-resistant epilepsy have a cortical malformation. However, the physiopathological mechanisms relating cortical malformations to epilepsy remain elusive.
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PMID:Genetic malformations of cortical development. 1672 81

Symptomatic West syndrome has heterogeneous backgrounds. Recently, two novel genes, ARX and CDKL5, have been found to be responsible for cryptogenic West syndrome or infantile spasms. Both are located in the human chromosome Xp22 region and are mainly expressed and play roles in fetal brain. Moreover, several genes responsible for brain malformations including lissencephaly, which is frequently associated with West syndrome or infantile spasms, have been found, and the mechanisms responsible for the neural network disorders in these brain malformations are rapidly being determined. Findings of animal and in vitro studies and mutation analyses in humans are delineating the molecular and cellular basis of West syndrome. Mutations of the ARX gene controlling the development of GABAergic interneurons exhibit pleiotropic effects including lissencephaly with a strong genotype-phenotype correlation. An expansion mutation of the first polyalanine tract of ARX is more strongly related to infantile spasms than is that of the second polyalanine tract. Although the phenotype of CDKL5 mutation is similar to Rett syndrome caused by MECP2 mutation, the former is characterized by early-onset seizures and association with West syndrome. Lissencephaly caused by LIS1 or DCX mutation frequently results in West syndrome, while lissencephaly due to ARX mutation is associated with the most severe form of epilepsy but never results in West syndrome nor infantile spasms. Both LIS1 and DCX participate in the development of GABAergic interneurons as well as pyramidal neurons, while ARX participates only in that of interneurons. Individuals with lissencephaly due to ARX mutation lack non-pyramidal or GABAergic interneurons. ARX is crucial for the development of GABAergic interneuron, so abnormal interneurons in patients with ARX mutation are thought to be implicated in the pathological mechanism, even though brain MRI is normal. Abnormal interneurons appear to play an essential role in the pathogenesis of West syndrome or infantile spasms, which can be considered an interneuronopathy.
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PMID:A new paradigm for West syndrome based on molecular and cell biology. 1680 28

This study investigates the clinical features of epilepsy in 20 patients with brain malformation. Epileptic seizures were recognized in 15 patients, 12 of whom had their first seizure by 1 year of age. Partial seizure was the initial seizure type in 10 patients. Epileptic seizures were controlled in only four patients. Patients with holoprosencephaly and lissencephaly had seizure onset by 3 months of age, resulting in the most severe neurologic outcome. Only two patients with porencephaly had epileptic seizures, and in one of those patients the seizures were well controlled. A wide variety of clinical features of epilepsy in patients with brain malformation was found. More immature anomalous brain lesions may be associated with an enhanced capacity of epilepsy and resultant refractory seizures.
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PMID:Enhanced capacity of epilepsy in brain malformation produced during early development. 1681 83

Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of alpha-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered alpha-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive.
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PMID:Walker-Warburg syndrome. 1688 26

Epilepsy is estimated to affect 1-2% of the world population, yet remains poorly understood at a molecular level. We have previously established the roundworm Caenorhabditis elegans as a model for investigating genetic susceptibilities to seizure-like convulsions in vivo. Here we investigate the behavioral consequences of decreasing the activity of nematode gene homologs within the LIS1 pathway that are associated with a human cortical malformation termed lissencephaly. Bioinformatic analysis revealed the nud-2 gene, encoding the worm homolog of mammalian effectors of LIS1, termed NDE1 and NDEL1. Phenotypic analysis of animals targeted by RNA interference (RNAi) was performed using a pentylenetetrazole (PTZ) exposure paradigm to induce convulsions. Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5, and CDKA-1) exhibited significant convulsions following PTZ and RNAi treatment. Strains harboring fluorescent markers for GABAergic neuronal architecture and synaptic vesicle trafficking were employed to discern putative mechanisms accounting for observed convulsion behaviors. We found that depletion of LIS1 pathway components resulted in defective GABA synaptic vesicle trafficking. We also utilized combinations of specific genetic backgrounds to create a sensitized state for convulsion susceptibility and discovered that convulsion effects were significantly enhanced when LIS-1 and other pathway components were compromised within the same animals. Thus, interactions among gene products with LIS-1 may mediate intrinsic thresholds of neuronal synchrony.
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PMID:Genetic interactions among cortical malformation genes that influence susceptibility to convulsions in C. elegans. 1699 38

Neuronal migrational disorders form a significant cause of psychomotor delay and intractable epilepsy in children. Pediatric neurology services are available at Sultan Qaboos University Hospital, Muscat, Oman, which is a tertiary care hospital for the whole country. The children undergoing evaluation for developmental delay and epilepsy formed the subjects of the study. Data were analyzed from children found to have neuronal migrational disorders on imaging (computed tomography [CT] or magnetic resonance imaging [MRI]). There were 40 cases of neuronal migrational disorders. Corpus callosum agenesis and lissencephaly or pachygyria formed the major group. There were 22 cases of corpus callosum agenesis, 12 of lissencephaly or pachygyria, 2 of schizencephaly, and 1 each of polymicrogyria, holoprosencephaly, hydranecephaly, and hemimegalencephaly. Nineteen of these 40 (47.5%) cases of neuronal migrational disorders had epilepsy. The break-down was 8 of 22 cases of corpus callosum agenesis (36%), 7 of 12 (58.3%) cases of lissencephaly or pachygyria, and 1 each of polymicrogyria, hydranencephaly, and hemimegalencephaly. The family history of developmental delay, similar to the index case, was present in two children with lissencephaly. However, the brain imaging did not reveal the abnormality. The types of seizures were infantile spasms in five, tonic-clonic in nine, myoclonic in two, partial in one, and mixed in five. Nineteen of 40 cases of neuronal migrational disorders had epilepsy. Only 2 of 19 (10.5%) with epilepsy had good seizure control. This raises the possibility of more and more surgical intervention in the management of such cases. Neuronal migrational disorders are related to exogenous and genetic factors from the 6th to 26th weeks of gestation. Molecular and genetic research is defining the mechanism of these disorders. This could help in early diagnosis, prevention, and eventual gene therapy in such conditions.
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PMID:Pattern of childhood epilepsies with neuronal migrational disorders in Oman. 1709 59

Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal recessive disorder of neuronal migration. Other similar cases of lissencephaly are reviewed.
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PMID:A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: report of a case and review of literature. 1727 2

We report on an apparently new syndrome in a consanguineous family with seven members, three of whom have cerebral anomalies including pachygyria and arachnoid cysts along with mental retardation and seizures. The two patients with seizure disorders also had multiple enlarged perivascular spaces seen in the white matter of the centrum semiovale. Our data provide a contribution to the accumulating knowledge on familial cerebral anomalies including arachnoid cysts and lissencephaly. Given the lack of mutation in known lissencephaly genes such as LIS1, 14-3-3epsilon, and DCX, this syndrome may constitute a new phenotype with autosomal recessive inheritance.
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PMID:Apparently novel genetic syndrome of pachygyria, mental retardation, seizure, and arachnoid cysts. 1734 67

Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes like the WEST-syndrome. The drug is usually well tolerated; rare serious complications may occur in some patients, including haemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of combined appearance of several severe VPA-associated side effects in a two- and a half-year-old girl with lissencephaly.
Seizure 2007 Sep
PMID:Reversible hepatotoxicity, pancreatitis, coagulation disorder and simultaneous bone marrow suppression with valproate in a 2-year-old girl. 1749 39

X-linked lissencephaly with absent corpus callosum and abnormal genitalia (XLAG) is caused by a mutation in the ARX gene. We herein report the clinical course of siblings with XLAG with a splicing mutation in ARX. Seizures were observed in utero. Cerebral atrophy was progressive postnatally, and fetal echoencephalography indicated that the atrophy might have started in the prenatal period. They had a typical phenotype, except that the genital abnormality of the younger brother was not remarkable. A portal-systemic shunt that has not been reported in cases with XLAG was seen in the older brother. The siblings had the different complications and severity of disease in spite of possessing the same mutation.
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PMID:[X-linked lissencephaly with absent corpus callosum and abnormal genitalia: a report of siblings followed from the prenatal period]. 1751 35


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