Multifocal epilepsy: the role of palliative resection - intractable frontal and occipital lobe epilepsy secondary to radiotherapy for acute lymphoblastic leukaemia.

Patients with multifocal epilepsy are often considered unsuitable for epilepsy surgery. We report an adolescent with intractable frontal and occipital lobe seizures, secondary to complications of treatment for acute lymphoblastic leukaemia as a young child. Chemotherapy and radiotherapy were complicated by bilateral, posterior leukoencephalopathy and later an acquired frontal cerebral cavernous malformation (CCM).

Benign occipital epilepsies of childhood: clinical features and genetics.

The early and late benign occipital epilepsies of childhood (BOEC) are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. Our aim was to explore the clinical features, classification and clinical genetics of these syndromes using twin and multiplex family studies to determine whether they are indeed distinct. Sixteen probands including seven twins were studied.

Factors influencing clinical features of absence seizures.

Purpose: The clinical features of absence seizures in idiopathic generalized epilepsy have been held to be syndrome-specific. This hypothesis is central to many aspects of epilepsy research yet has not been critically assessed. We examined whether specific factors such as epilepsy syndrome, age, and state determine the features of absence seizures.

Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a relatively benign epilepsy syndrome with few comorbidities. Here we describe two families with unusually severe ADNFLE, with associated psychiatric, behavioral, and cognitive features. Detailed clinical data on 17 affected individuals were obtained, and genotyping of microsatellite markers, linkage analysis, and sequencing of candidate genes was performed.

X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment.

Epilepsy and mental retardation limited to females (EFMR) is a disorder with an X-linked mode of inheritance and an unusual expression pattern. Disorders arising from mutations on the X chromosome are typically characterized by affected males and unaffected carrier females. In contrast, EFMR spares transmitting males and affects only carrier females.

Human nocturnal frontal lobe epilepsy: pharmocogenomic profiles of pathogenic nicotinic acetylcholine receptor beta-subunit mutations outside the ion channel pore.

Certain mutations in specific parts of the neuronal nicotinic acetylcholine receptor (nAChR) subunit genes CHRNA4, CHRNB2, and probably CHRNA2, can cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). All but one of the known causative mutations are located in the second transmembrane region (TM2), which serves as the major ion poreforming domain of the receptor. Functional characterization of these ADNFLE mutations has shown that although each mutant exhibits specific properties, they all confer a gain of function with increased sensitivity to acetylcholine.

Gene expression analysis in absence epilepsy using a monozygotic twin design.

Purpose: To identify genes involved in idiopathic absence epilepsies by analyzing gene expression using a monozygotic (MZ) twin design.

Methods: Genome-wide gene expression in lymphoblastoid cell lines (LCLs) was determined using microarrays derived from five discordant and four concordant MZ twin pairs with idiopathic absence epilepsies and five unaffected MZ twin pairs. Gene expression was analyzed using three strategies: discordant MZ twins were compared as matched pairs, MZ twins concordant for epilepsy were compared to control MZ twins, and a singleton design of affected versus unaffected MZ twin individuals was used irrespective of twin pairing.

Navigating the channels and beyond: unravelling the genetics of the epilepsies.

Genetic factors are now recognised to have an even more important role in epilepsies than previously appreciated. Rare mendelian forms of epilepsy are now well recognised, and there is evidence of complex inheritance due to multiple susceptibility genes in most idiopathic epilepsies. The complexities of epilepsy classification and the variety of clinical genetic methodologies (family aggregation, twin, and multiplex family studies) have led to an apparently confusing picture.

Epilepsy and mental retardation limited to females: an under-recognized disorder.

Epilepsy and Mental Retardation limited to Females (EFMR) which links to Xq22 has been reported in only one family. We aimed to determine if there was a distinctive phenotype that would enhance recognition of this disorder. We ascertained four unrelated families (two Australian, two Israeli) where seizures in females were transmitted through carrier males.

Association of a nicotinic receptor mutation with reduced height and blunted physostigmine-stimulated growth hormone release.

Background: Pulsatile GH secretion from the anterior pituitary is a key mediator of human growth regulation and is affected by a number of genetic and environmental factors. Activation of neuronal nicotinic acetylcholine (nACh) receptors promotes GH release, but the role of these receptors in growth regulation is unknown.

Aim: Our aim was to assess the effect of a mutation in the alpha4 subunit of the nACh receptor on cholinergic-mediated GH release.

Multicentre search for genetic susceptibility loci in sporadic epilepsy syndrome and seizure types: a case-control study.

Background: The Epilepsy Genetics (EPIGEN) Consortium was established to undertake genetic mapping analyses with augmented statistical power to detect variants that influence the development and treatment of common forms of epilepsy.

Methods: We examined common variations across 279 prime candidate genes in 2717 case and 1118 control samples collected at four independent research centres (in the UK, Ireland, Finland, and Australia). Single nucleotide polymorphism (SNP) and combined set-association analyses were used to examine the contribution of genetic variation in the candidate genes to various forms of epilepsy.

GEFS+ where focal seizures evolve from generalized spike wave: video-EEG study of two children.

Focal seizures often secondarily generalize but the reverse is much less frequently documented. The idiopathic generalized epilepsies have the EEG signature of generalized, or bilaterally synchronous spike wave activity and although focal features can be seen, seizures are usually generalized once they commence. Although focal seizures can be seen in some syndromes, it is not well recognized that generalized seizures can become focal during the attack.

Extended spectrum of idiopathic generalized epilepsies associated with CACNA1H functional variants.

Objective: The relationship between genetic variation in the T-type calcium channel gene CACNA1H and childhood absence epilepsy is well established. The purpose of this study was to investigate the range of epilepsy syndromes for which CACNA1H variants may contribute to the genetic susceptibility architecture and determine the electrophysiological effects of these variants in relation to proposed mechanisms underlying seizures.

Methods: Exons 3 to 35 of CACNA1H were screened for variants in 240 epilepsy patients (167 unrelated) and 95 control subjects by single-stranded conformation analysis followed by direct sequencing.

Absence of mutations in the LGI1 receptor ADAM22 gene in autosomal dominant lateral temporal epilepsy.

Mutations in the LGI1 (leucine-rich, glioma inactivated 1) gene are found in less than a half of the families with autosomal dominant lateral temporal epilepsy (ADLTE), suggesting that ADLTE is a genetically heterogeneous disorder. Recently, it was shown that LGI1 is released by neurons and becomes part of a protein complex at the neuronal postsynaptic density where it is implicated in the regulation of glutamate-AMPA neurotransmission. Within this complex, LGI1 binds selectively to a neuronal specific membrane protein, ADAM22 (a disintegrin and metalloprotease).

Early seizures: causal events or predisposition to adult epilepsy?

Past studies have been unable to confirm whether early seizures predispose to epilepsy in adults. Seizures in infancy were classically thought to cause brain lesions that led to epilepsy in adulthood. However, these infants were not thought to have epilepsy, but acute events that included seizures.

Is photosensitive epilepsy less common in males due to variation in X chromosome photopigment genes?

Photosensitive epilepsy is less frequent among males than females. Red is the most epileptogenic color. The X-linked red pigment gene contains the polymorphism Ser180Ala; the Ser180 allele increases red sensitivity.

A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel.

Seizure susceptibility is high in human infants compared to adults, presumably because of developmentally regulated changes in neural excitability. Benign familial neonatal-infantile seizures (BFNIS), characterized by both early onset and remission, are caused by mutations in the gene encoding a human sodium channel (NaV1.2).

Channelopathies in idiopathic epilepsy.

Approximately 70% of all patients with epilepsy lack an obvious extraneous cause and are presumed to have a predominantly genetic basis. Both familial and de novo mutations in neuronal voltage-gated and ligand-gated ion channel subunit genes have been identified in autosomal dominant epilepsies. However, patients with dominant familial mutations are rare and the majority of idiopathic epilepsy is likely to be the result of polygenic susceptibility alleles (complex epilepsy).

SCN2A mutations and benign familial neonatal-infantile seizures: the phenotypic spectrum.

Mutations of the sodium channel subunit gene SCN2A have been described in families with benign familial neonatal-infantile seizure (BFNIS). We describe two large families with BFNIS and novel SCN2A mutations. The families had 12 and 9 affected individuals, respectively, with phenotypes consistent with BFNIS.

Vaccination, seizures and 'vaccine damage'.

Purpose Of Review: Concerns about the safety of vaccination have plagued the community, with reduction in vaccine uptake resulting in increased risk of epidemics. Vaccination has been implicated in the cause of febrile seizures, 'vaccine encephalopathy' and autistic spectrum disorders. Evaluation of alleged associations is complicated by evolution in the vaccination field.

The spectrum of SCN1A-related infantile epileptic encephalopathies.

The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life.