PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Epilepsy, Benign Neonatal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMedDate not supplied

[Idiopathic epileptic syndromes of the newborn].

INTRODUCTION: Seizures during the neonatal period are the characteristic clinical expression of dysfunction of the nervous system. Not all the seizures seen during the neonatal period are due to epilepsy which only occurs in 10%. DEVELOPMENT: The aetiology of neonatal seizures is very varied and is mainly due to different types of aggression to the brain during this early stage of life. Epileptic syndromes are very rare during the neonatal period. In general the prognosis is very bad as occurs in infantile epileptic encephalopathy of early onset or myoclonic encephalopathy of early onset. However, the International League Against Epilepsy (ILAE) has identified and recognized some idiopathic epileptic syndromes of the neonatal period with a somewhat better prognosis. Two major groups have been established including the benign neonatal epilepsies (benign idiopathic neonatal epilepsies and benign familial neonatal seizures) and the group of status epilepticus (severe idiopathic status epilepticus). CONCLUSION: We analyze the different types of epilepsy of the newborn, form of onset, current knowledge of molecular biology, treatment and prognosis.

Epilepsy, Benign Neonatal↗
PubMed2006

Subthreshold changes of voltage-dependent activation of the K(V)7.2 channel in neonatal epilepsy.

Benign familial neonatal convulsions (BFNC) is an epileptic disorder caused by dominant mutations in the genes KCNQ2 and KCNQ3 encoding the K+ channels K(V)7.2 and K(V)7.3. We identified two novel KCNQ2 mutations in two BFNC families. One mutation predicted a truncated protein (S247X) that lacks the channel's pore region, the other resulted in the amino acid substitution S122L in the S2 segment of K(V)7.2. In comparison to wild-type (WT) K(V)7.2, functional analysis of S122L mutant channels in Xenopus oocytes revealed a significant positive shift and increased slope of the activation curve leading to significant current reduction in the subthreshold range of an action potential (75% reduction at -50 mV). Our results establish an important role of the K(V)7.2 S2 segment in voltage-dependent channel gating and demonstrate in a human disease that subthreshold voltages are likely to represent the physiologically relevant range for this K+ channel to regulate neuronal firing.

Animals↗
PubMed1999

[Benign familial neonatal convulsions: a model of idiopathic epilepsy].

Benign neonatal familial convulsions have been recognized as a distinctive epileptic syndrome since 1964. This rare epileptic syndrome was classified in the category of idiopathic generalized epilepsies. Recently, mutations of potassium channel genes (KCNQ2, KCNQ3) were identified as responsible for this autosomic dominant epileptic syndrome. Generalized tonico-clonic seizures start at the second or third day after birth in children with no prenatal or perinatal pathological history. Interictal EEG is normal. This epilepsy is age-dependent: less than ten percent of children present seizures later in life. Despite their rarity, BNFC represent a useful model to understand the pathophysiology of idiopathic age dependant epilepsies.

Electroencephalography↗
PubMed1998

A potassium channel mutation in neonatal human epilepsy.

Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (KCNQ2) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five-base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.

Action Potentials↗
PubMedDate not supplied

[Channelopathies in neurology].

INTRODUCTION: The main function of ionic channels are the conduction, recognition and selection of specific ions. They open and close in respond answer to electrical, mechanical and chemical stimulus, acting in the excitation or transmission of diverse tissues. DEVELOPMENT: The clinical and molecular manifestations of channelophathies are varied and use to shown up in continuous or paroxystic ways. Alteration of Ca channels cause muscle dysfunction periodic paralysis with or without potassium changes, myasthenia or myasthenic disorders, like Lambert Eaton syndrome, amyotrophic lateral sclerosis, Central Core disease, malignant hyperthermia. Cl and Na channels alterations produce myotonic diseases: Thomsen, Becker and paramyothonies, potassium sensible paralysis, fluctuant congenital myotonic, Andersen s syndrome. Channelopathies also produce various episodic ataxia type 1, type 2, spinocerebellar 6 and familial hemiplegic migraine. Abnormal paroxystic movements are present as channelophaties: episodic nocturnal dystonia, paroxystic dyskinesia. In some families are associates abnormal episodic movements and epilepsy. Several epileptic syndromes are also related with channels dysfunction: frontal lobe nocturnal epilepsy, choreoatetosis epilepsy, benign neonatal convulsions, generalized epilepsy with febrile convulsions plus. CONCLUSIONS: Voltage gated channels dysfunction are related to diseases with episodic phenomena or permanent conditions on muscle or neuronal tissues, with clinical and genetic heterogenous manifestations.

Humans↗
PubMed2000

Multifactorial pathogenesis of neonatal seizures--relationships to the benign partial epilepsies.

Elevated incidence of neonatal seizures (NS) in children with idiopathic partial epilepsies, as well as reports on the transition of NS into benign partial epilepsy, point to pathogenetic relationships between these conditions. Further insight into the nature of these relationships can be expected only from NS patients with long-term follow-up, which includes the age range of maximum manifestation of subsequent seizures or epilepsies (SSE), and age-dependent genetic EEG traits. A sample of such cases will necessarily be selected and thus prohibit any quantitative inferences regarding the incidence of SSE and special EEG characteristics. Nevertheless, the data provide new aspects with regard to a possibly multifactorial pathogenesis of NS and SSE. Children in the present study were selected applying the following inclusion criteria: cerebral seizures during the first 14 days of life; follow up of more than two years with at least two EEG recordings beyond the age of two. Children with metabolic NS or subsequent West syndrome were not included. Seventy-six cases were confirmed, 42 with SSE, 34 without. The incidence of EEG symptoms of a generalized genetic seizure liability (theta rhythms, generalized spikes and waves, photoparoxysmal response) was significantly elevated, equally in children with and without SSE. Beyond the age of two years, 50% of the probands had focal sharp waves foci characteristic of idiopathic partial epilepsy (e.g. rolandic epilepsy). Among SSE, febrile convulsions and partial epilepsies with benign course dominated. Idiopathic generalized epilepsies were not observed. These findings indicate that in a certain proportion of cases, NS have genetic factors in common with idiopathic partial epilepsies. Quantitative representative data cannot be obtained to determine the incidence of such pathogenetic mechanisms in NS and SSE.

Adolescent↗
PubMed1999

Benign familial neonatal epilepsy with mutations in two potassium channel genes.

The significant progress made over the past year in understanding the basis for a form of neonatal seizures can be attributed to the successful positional cloning of two new voltage-gated potassium channel genes. Expression studies have increased our understanding of the biology of these channels and their role in epilepsy.

Chromosomes, Human, Pair 20↗
PubMed2005

Ion channels and epilepsy.

The role of voltage-gated and ligand-gated ion channels in epileptogenesis of both genetic and acquired epilepsies, and as targets in the development of new antiepileptic drugs (AEDs) is reviewed. Voltage-gated Na+ channels are essential for action potentials, and their mutations are the substrate for generalised epilepsy with febrile seizures plus and benign familial neonatal infantile seizures; Na+ channel inhibition is the primary mechanism of carbamazepine, phenytoin and lamotrigine, and is a probable mechanism for many other classic and novel AEDs. Voltage-gated K+ channels are essential in the repolarisation and hyperpolarisation that follows paroxysmal depolarisation shifts (PDSs), and their mutations are the substrate for the benign neonatal epilepsy and episodic ataxia type 1; they are new targets for AEDs such as retigabine. Voltage-gated Ca2+ channels are involved in neurotransmitter release, in the sustained depolarisation-phase of PDSs, and in the generation of absence seizures; their mutations are a substrate for juvenile myoclonic epilepsy and the absence-like pattern seen in some mice; the antiabsence effect of ethosuximide is due to the inhibition of thalamic T-type Ca2+ channels. Voltage-gated Cl- channels are implicated in GABA(A) transmission, and mutations in these channels have been described in some families with juvenile myoclonic epilepsies, epilepsy with grand mal seizures on awakening or juvenile absence epilepsy. Hyperpolarisation-activated cation channels have been implicated in spike-wave seizures and in hippocampal epileptiform discharges. The Cl- ionophore of the GABA(A) receptor is responsible for the rapid post-PDS hyperpolarisation, it has been involved in epileptogenesis both in animals and humans, and mutations in these receptors have been found in families with juvenile myoclonic epilepsy or generalised epilepsy with febrile seizures plus; enhancement of GABA(A) inhibitory transmission is the primary mechanism of benzodiazepines and phenobarbital and is a mechanistic approach to the development of novel AEDs such as tiagabine or vigabatrin. Altered GABA(B)-receptor function is implicated in spike-wave seizures. Ionotropic glutamate receptors are implicated in the sustained depolarisation phase of PDS and in epileptogenesis both in animals and humans; felbamate, phenobarbital and topiramate block these receptors, and attenuation of glutamatergic excitatory transmission is another new mechanistic approach. Mutations in the nicotinic acetylcholine receptor are the substrates for the nocturnal frontal lobe epilepsy. The knowledge of the role of the ion channels in the epilepsies is allowing the design of new and more specific therapeutic strategies.

Action Potentials↗
PubMed2001

Ion channel variation causes epilepsies.

The discovery of genetically transmissible form of epilepsy associated with a mutation in a gene that codes for a subunit of a ligand-gated channel shined a new light in this field of neurological diseases. Because this gene (CHRNA4) codes for a neuronal nicotinic acetylcholine receptor subunit, functional studies could be designed to evaluate the alterations caused by this mutation. Since this initial observation, five mutations were identified and determination of their functional properties initiated. These experiments were extended to pairwise expression of the control and mutated allele to mimic the heterozygote human genotype. The first common functional trait identified so far, in four of these mutants, is an increased sensitivity to the acetylcholine, suggesting that these mutations may cause a gain of function. An alternative possibility that cannot be excluded is that conditions in the brain are such that these higher responding receptors may be more prone to desensitization. The importance of ionic channels as cause of epilepsies was further demonstrated with the identification of the association between the benign neonatal epilepsy and mutations in genes coding for potassium channel subunits (KCNQ2, KCNQ3). Additional evidences were brought by the identification of mutations in voltage-dependent sodium channels (SCN1A, SCN1B) in a form of generalized epilepsy with febrile seizures.

Acetylcholine↗
PubMed2002

Genetic identifiers of epilepsy.

Epilepsy affects >0.5% of the world's population and has a large genetic component. The most common human genetic epilepsies display a complex pattern of inheritance, and the identity of the susceptibility genes is largely unknown despite recent advances in molecular biology. However, genetic identifiers of certain types of epilepsy with neurodegenerative characteristics and of a small number of familial idiopathic epilepsies have been uncovered to date. This article reviews recent progress made in molecular genetics of epilepsy, focusing mostly on idiopathic epilepsy together with our own discovery of novel mutations in the genes of autosomal dominant nocturnal frontal lobe epilepsy and benign familial neonatal convulsions (BFNCs), and the genetic locus of benign adult familial myoclonic epilepsy. Pathogenesis of epilepsy as a channelopathy and of BFNC also is discussed.

Adult↗
PubMedDate not supplied

Benign familial neonatal convulsions: generalized epilepsy?

A 3-year-old girl is presented with benign familial neonatal convulsions. She had seizures during the neonatal period and at age 3 months. Seizure manifestations and ictal electroencephalography indicated that she had not experienced generalized seizures but partial seizures, although international classifications of epilepsy define benign familial neonatal convulsions as generalized epilepsy.

Child, Preschool↗
PubMed2006

A novel splicing mutation in KCNQ2 in a multigenerational family with BFNC followed for 25 years.

PURPOSE: A large multigenerational family with benign familial neonatal convulsions (BFNC) was revisited to identify the disease-causing mutation and to assess long-term outcome. METHODS: We supplemented the original data with recent clinical and neurophysiologic data on patients and first-degree relatives, including information on seizure recurrence. We conducted linkage analysis at the EBN1 and EBN2 loci, followed by mutation analysis of KCNQ2. We evaluated the qualitative effect of the KCNQ2 mutation at the messenger RNA (mRNA) level by using reverse-transcribed total RNA isolated from leukocytes. RESULTS: Thirteen relatives had a history of neonatal convulsions, 11 of whom showed remission within 2 months. One patient showed an atypical course of neonatal convulsions, developing photosensitive myoclonic epilepsy at age 13 years. We found suggestive linkage of the BFNC phenotype to the 20q13-EBN1 locus (lod score, 2.03) and an intronic mutation IVS14-6 C>A in KCNQ2 segregating with the trait in all affected members, but absent in 100 unrelated control subjects. This mutation creates a new, preferentially used, splice site. Alternative splicing adds 4 nt containing a premature stop codon to the transcript, resulting in a truncated protein after position R588. CONCLUSIONS: We detected and characterized a novel splicing mutation in the brain-specific KCNQ2 gene by using easily accessible blood leukocytes. Aberrant splicing cosegregates with BFNC but not with photosensitivity.

Adolescent↗
PubMed2000

[Ion channels and epilepsy].

OBJECTIVE: We review the role of ligand-gated ion channels and voltage-gated ion channels as a substrate for the epileptogenesis and as targets in the development of new antiepileptic drugs. DEVELOPMENT: Voltage-gated calcium channels are involved in the release of neurotransmitters, in the sustained depolarization-phase of paroxysmal depolarisation shifts (PDS), and in the generation of absences; they are also the genetic substrate of generalized tonic-clonic convulsions and absence-like pattern seen in some mice. The voltage-gated potassium channel has been implicated in the hyperpolarization-phase of PDS, it is the genetic substrate of the long QT syndrome, benign neonatal epilepsy, and episodic ataxia/myokymia syndrome, and it is the target of some antiepileptic drugs which activate this channel. The voltage-gated sodium channel is the target of most of the classical and newer antiepileptic drugs; it is also the substrate for generalized epilepsy with febrile seizures plus. The sodium channel of the nicotinic acetylcholine receptor is the substrate for nocturnal frontal lobe epilepsy. The sodium channels of the AMPA and KA glutamate receptors have been proposed as substrate for juvenile absence epilepsy and are a target for new antiepileptic drugs which inhibit it. The calcium channel of the NMDA glutamate receptor has been implicated in the sustained depolarization-phase of PDS and in epileptogenesis after kindling and is a main target for new antiglutamate drugs. The chloride channel of the GABAA receptor is responsible for the rapid hyperpolarization of PDS, it has been involved in epileptogenesis after kindling, it may be the substrate of the Angelman syndrome, and it is activated by many classical and new antiepileptic drugs. CONCLUSION: The knowledge of the role of the ion channels in the epilepsies is allowing the design of new and more specific therapeutic strategies.

Angelman Syndrome↗
PubMed2001

Short-term outcomes of children with febrile status epilepticus.

Febrile status epilepticus (SE) represents the extreme end of the complex febrile seizure spectrum. If there are significant sequelae to febrile seizures, they should be more common in this group. We have prospectively identified 180 children aged 1 month to 10 years who presented with febrile SE over a 10-year period in Bronx, New York, and Richmond, Virginia. They were compared with 244 children who presented with their first febrile seizure (not SE) in a prospective study done in the Bronx. The mean age of the children with febrile SE was 1.92 years, and of the comparison group, 1.85 years. Duration of SE was 30-59 min in 103 (58%), 60-119 min in 43 (24%), and > or =120 min in 34 (18%). Focal features were present in 64 (35%) of cases. There were no deaths and no cases of new cognitive or motor handicap. Children with febrile SE were more likely to be neurologically abnormal (20% vs. 5%; p < 0.001), to have a history of neonatal seizures (3% vs. 0; p = 0.006) and a family history of epilepsy (11% vs. 5%; p = 0.05) and less likely to have a family history of febrile seizures (15% vs. 27%; p = 0.01) than were children in the comparison group. The short-term morbidity and mortality of febrile SE are low. There are differences in the types of children who have febrile SE compared with those who experience briefer febrile seizures. Long-term follow-up of this cohort may provide insight into the relationship of prolonged febrile seizures and subsequent mesial temporal sclerosis.

Age Distribution↗
PubMed2004

Neonatal seizures and limb malformations associated with liver-specific complex IV respiratory chain deficiency.

An eight-week-old infant, the fourth child of consanguineous parents presented with intractable neonatal seizures. The mother had two previous miscarriages. The infant initially presented on day one with multifocal myoclonus, complex partial and generalised tonic-clonic seizures. On examination, there were dysmorphic hands and feet, with absent nails and terminal phalanges of the fingers and toes, hepatomegaly, marked axial and peripheral hypotonia and severe global developmental delay. Ophthalmological assessment showed 'salt and pepper' pigmentary retinopathy. The urinary organic acid profile revealed a marked increase in tricarboxylic acid metabolites. Urinary phosphate reabsorption was reduced at 84%. Type I fibre atrophy was seen on muscle histology, and a cytochrome c oxidase deficiency was found only on enzymology of liver tissue. Limb malformations associated with respiratory chain defects have rarely been reported. To our knowledge, this child has the most severe limb anomaly associated with a tissue-specific complex IV respiratory chain defect.

Abnormalities, Multiple↗
PubMedDate not supplied

A genetic study of the human low-voltage electroencephalogram.

The studied phenotype, the low-voltage electroencephalogram (LVEEG), is characterized by the absence of an alpha rhythm from the resting EEG. In previous studies, evidence was found for a simple autosomal-dominant mode of inheritance of the LVEEG. Such a polymorphism in brain function can be used as a research model for the stepwise elucidation of the molecular mechanism involved in those aspects of neuronal activity that are reflected in the EEG. Linkage with the variable number of tandem repeats (VNTR) marker CMM6 (D20S19) and localization of an LVEEG (EEGV1) gene on 20q have previously been reported, and genetic heterogeneity has been demonstrated. This latter result has been corroborated by studying new marker (MS214). The phenotype of the LVEEG is described here in greater detail. Its main characteristic is the absence of rhythmic alpha activity, especially in occipital leads, whereas other wave forms such as beta or theta waves may be present. Analysis of 17 new families (some of them large), together with 60 previously described nuclear families, supports the genetic hypothesis of an autosomal-dominant mode of inheritance. Problems connected with the analysis of linkage heterogeneity, exclusion mapping, and the study of multipoint linkage are discussed. A possible explanation of the localization of LVEEG in the close vicinity of another gene influencing synchronization of the normal EEG, the gene for benign neonatal epilepsie, is given.

Aging↗