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

Lafora body disease is one cause of progressive myoclonus epilepsy. It typically presents in the second decade with generalized seizures, myoclonus and then intellectual decline. Death is usual within 10 years. Diagnosis may be made by biopsy of skin, muscle, liver or brain. We present four siblings who were normal until their mid-twenties, but then developed intellectual decline, followed by myoclonus. Although a rare form of Lafora body disease has been described that follows a more benign course, may be of later onset, and whose pathology is subtly different, this family is so far unique in terms of the late presentation of otherwise typical Lafora body disease.
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PMID:Familial Lafora body disease of late onset: report of four cases in one family and a review of the literature. 900 44

Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder, characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The gene for the proteinase inhibitor cystatin B was recently localized in the EPM1 critical region, and mutations were identified in two EPM1 families. We have identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1 families from northern Africa and Europe. The 426G-->C change in exon 1 results in a Gly4Arg substitution and is the first missense mutation described that is associated with EPM1. Molecular modeling predicts that this substitution severely affects the contact of cystatin B with papain. Mutations in the invariant AG dinucleotides of the acceptor sites of introns 1 and 2 probably result in abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift and truncates the protein. Therefore, these four mutations are all predicted to impair the production of functional protein. These mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. The remaining two sequence changes, 431G-->T and 2575A-->G, probably represent polymorphic variants. In addition, a tandem repeat in the 5' UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It is peculiar that in the majority of patients no mutations exist within the exons and splice sites of the cystatin B gene.
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PMID:Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1). 901 7

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.
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PMID:Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1. 905 46

Since 1987, we have diagnosed 10 patients, 4 males and 6 females, aged 2-11 years at the last evaluation, who all met the following criteria of severe myoclonic epilepsy in infancy (SMEI): generalized or unilateral long-lasting febrile clonic seizures in the first year of life; the subsequent appearance of myoclonic seizures and other types of seizure (partial seizures, atypical absences and convulsive status epilepticus); and neuropsychological deterioration for a certain period. Family histories of epilepsy and febrile seizures could be traced in 1 and 3 cases, respectively. None of them had previous personal history of brain insult. Electroencephalographic (EEGic) recordings in febrile seizure stage were normal; and continuous prophylaxis with phenobarbital failed to prevent the recurrence of febrile seizures. EEG studies in myoclonic stage showed generalized spike-and-waves, polyspike-and-waves, focal abnormalities and/or photosensitivity. The seizures were highly resistant to antiepileptic drugs. Our experiences suggested that comedication of valproic acid, clonazepam and carbamazepine may be most effective in treatment of the diverse seizures including myoclonic seizures, myoclonic-tonic-clonic seizures, atypical absences and partial seizures. Myoclonic seizures and atypical absences diminished in parallel to a clear-cut decrease in generalized abnormalities on EEG in 4 cases aged more than 7 years. However, the partial seizures, secondarily generalized seizures and status epilepticus were still present. Further investigations should aim to identify the underlying etiology and to search more effective treatment.
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PMID:Severe myoclonic epilepsy in infancy: evolution of electroencephalographic and clinical features. 907 79

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder that occurs with a low frequency in many populations but is more common in Finland and the Mediterranean region. It is characterized by stimulus-sensitive myoclonus and tonic-clonic seizures with onset at age 6-15 years, typical electroencephalographic abnormalities and a variable rate of progression between and within families. Following the initial mapping of the EPM1 gene to chromosome 21 (ref. 6) and the refinement of the critical region to a small interval, positional cloning identified the gene encoding cystatin B (CST6), a cysteine protease inhibitor, as the gene underlying EPM1 (ref. 10). Levels of messenger RNA encoded by CST6 were dramatically decreased in patients. A 3' splice site and a stop codon mutation were identified in three families, leaving most mutations uncharacterized. In this study, we report a novel type of disease-causing mutation, an unstable 15- to 18-mer minisatellite repeat expansion in the putative promoter region of the CST6 gene. The mutation accounts for the majority of EPM1 patients worldwide. Haplotype data are compatible with a single ancestral founder mutation. The length of the repeat array differs between chromosomes and families, but changes in repeat number seem to be comparatively rare events.
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PMID:Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1. 909 Mar 86

Changes in seizure type of severe myoclonic epilepsy (SME) in infancy were reviewed retrospectively in 14 patients (11 males and 3 females) who were followed-up to the age of 7 years or more. The observation period ranged from 5 to 16 years with a mean of 10 years. During the follow-up, three or four types of seizures were seen per patient, but the pattern of appearance and disappearance of each seizure type varied considerably among the patients. Tonic-clonic convulsion, either generalized or unilateral, was seen most consistently through the entire course, and it continued to the end of follow-up in 11 patients (79%). On the contrary, myoclonic seizure, complex partial seizure, and atypical absence often disappeared and reappeared repeatedly during the course. In SME, seizure symptoms varied widely among patients in comparison with other neurological symptoms, and the most consistent core seizure type was tonic-clonic convulsions.
Seizure 1997 Jun
PMID:Severe myoclonic epilepsy in infancy: evolution of seizures. 920 51

Patients affected with progressive myoclonus epilepsy of the Lafora type present during late adolescence with a characteristic EEG pattern and Lafora bodies seen on skin biopsy. The critical region for the Lafora gene has been localised to chromosome 6q24 flanked by the dinucleotide repeat markers D6S292 and D6S420. This study for linkage of markers from the candidate gene region was performed in a previously unpublished family affected with Lafora disease. EEG and skin biopsy evaluation for Lafora bodies were performed on five of eight family members followed for seizure activity. Haplotype and linkage analysis of DNA from five family members were carried out using the nine dinucleotide repeat markers reported in the common region of homozygosity by Serratosa et al in 1995. The present study of an additional family affected by Lafora disease has narrowed the 17 cM critical region for the Lafora disease gene on chromosome 6q24 to a 4 cM region flanked by markers D6S308 and D6S311.
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PMID:Identification of a recombination event narrowing the Lafora disease gene region. 922 70

CGP 56999A ([3-[1-(R)-[(3-cyclohexylmethyl)hydroxyphosphinyl]-2-(S)- hydroxy-propyl] amino]ethyl]-benzoic acid) is a potent GABAB receptor antagonist showing much more pronounced convulsant features in mice than do other previously studied GABAB receptor antagonists. The goal of this study was to elucidate the physiological mechanisms underlying this effect. In mice a dose of 0.6 mg/kg intraperitoneal (i.p.) CGP 56999A elicited behavioral activation and stereotypy with periods of intensive scratching and grooming. At 1 mg/kg i.p. most mice displayed myoclonic seizure-like episodes lasting several min. Pretreatment with the lower dose of 0.6 mg/kg i.p. also induced seizures after treatment with a subthreshold dose of pentylenetetrazole (40 mg/kg i.p.). In rats a dose of 3 mg/kg CGP 56999A (i.p.) induced convulsions of tonic-clonic nature. Intracellular sharp microelectrode recordings from rat cortical neurons in slices revealed no paroxysmal actions of CGP 56999A (10 microM). Similar to other GABAB receptor antagonists, CGP 56999A suppressed the late inhibitory postsynaptic potential (i.p.s.p.), but had no effect on the excitatory postsynaptic potential (e.p.s.p.) in the cortex. In cortical slices exposed to picrotoxin (10 microM), the compound evoked pronounced, spontaneous and intense epileptiform discharges. In conclusion, these findings demonstrated that the convulsive feature of the potent GABAB receptor antagonist, CGP 56999A, may be due to suppression of the late i.p.s.p., which becomes apparent in the intact brain only, whereas this action remains undetected in untreated brain slices. This remarkable discrepancy between in vitro and in vivo may be a consequence either of disruption of neuronal circuits during slice preparation or of the pronounced hyperpolarization of pyramidal neurons, at least in the case of cortical slice preparations.
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PMID:Comparative in vivo and in vitro studies with the potent GABAB receptor antagonist, CGP 56999A. 931 26

Clozapine elicits dose-dependent myoclonic jerks in partially restrained rats and induces paroxysmal electroencephalographic changes, myoclonus, and convulsive seizures in a small but significant percentage of patients. With the hypothesis that the central excitatory effects of clozapine may relate to the unique therapeutic activity of this agent, rats were administered repeated alternate day or weekly very low dose (1 mg/kg) injections of clozapine in an attempt to induce the central excitatory effect through sensitization or kindling. Although initial administrations of this dose elicited no motor response or other behavioral change, repeated administration of the same low dose on either the alternate-day or weekly schedule caused increasing numbers of myoclonic seizure-like jerks (MJs) reaching 75-110 MJs/hour by the sixth clozapine injection. Clozapine-sensitized animals exhibited a significantly different pattern of early gene expression in two subcortical sites compared with vehicle-treated controls. These findings may have importance for the treatment of psychosis.
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PMID:Sensitization with clozapine: beyond the dopamine hypothesis. 934 26

Based on small numbers of patients, it is possible to make the following suggestions rather than categorical statements. For myoclonic seizures and epilepsies which are not otherwise specified, valproate seems of proven efficacy. Ethosuximide may be a useful adjunct. The exact place of lamotrigine, which controls some myoclonia and makes them worse in other patients, requires further study. The findings are clearer when specific syndromes are considered. Valproate is the treatment of first choice for benign myoclonic epilepsy in infants, myoclonic astatic epilepsy, epilepsy with myoclonic absences, eyelid myoclonia with absences, juvenile myoclonic epilepsy and progressive myoclonus epilepsy. The addition of ethosuximide to valproate can be helpful to those with myoclonic absences, where this combination appears more beneficial than either valproate or ethosuximide alone and in eyelid myoclonia with absences. Lamotrigine can be effective therapy for juvenile myoclonic epilepsy and eyelid myoclonia with absences when used alone and, in conjunction with other antiepileptic drugs (AED) (usually valproate) for early myoclonic encephalopathy, myoclonic-astatic epilepsy and particularly, epilepsy with myoclonic absences. The myoclonia of infantile neuronal ceroid lipofuscinosis respond to lamotrigine. Severe myoclonic epilepsy of infants usually worsens with lamotrigine, but occasionally, children improve. Zonisamide added to clonazepam and valproate or a barbiturate, can reduce the cascade of myoclonia in progressive myoclonus epilepsies for at least 2 years, but relapse may occur thereafter.
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PMID:Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. 947 47


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