Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clozapine is an 'atypical' neuroleptic that improves symptoms of many patients with schizophrenia whose illness is resistant to treatment with other neuroleptics. Unlike the 'typical neuroleptics (chlorpromazine, haloperidol), clozapine does not induce extrapyramidal symptoms such as Parkinsonism and tardive dyskinesia in humans or catalepsy in the rat. However, clozapine frequently causes epileptiform EEG changes and causes seizures in 3-5% of patients treated with this drug in therapeutic doses. Clozapine also induces dose dependent myoclonus in the partially restrained rat. In the experiments reported here, partially restrained rats were administered repeated alternate day or weekly low, fixed doses of clozapine (1 mg/kg). This dose initially caused no behavioral change. Following the third and subsequent administrations, the same dose elicited an increasing number of myoclonic seizure-like jerks reaching 140/h following the 15th injection in rats receiving the same low dose of clozapine on alternate days and 160/h following the 9th injection in animals that received the same dose once weekly. These effects are consistent with kindling, i.e. a progressive increase of brain excitability following repeated administration of a fixed subconvulsive dose of an excitatory agent. Clozapine kindled animals exhibited a significantly different pattern of early gene expression in ventral tegmental area, origin of the mesolimbic-mesocortical dopamine system and in the anterior thalamic nuclei, compared with saline treated controls subjected to exactly the same recording conditions. The evidence of central nervous system excitation with clozapine may be important to the unique therapeutic effect of this atypical antipsychotic in the treatment of symptoms, especially the deficit symptoms, of schizophrenia.
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PMID:Kindling with clozapine: behavioral and molecular consequences. 898 8

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

Three families with a common clinical feature of adult onset myoclonus epilepsy were studied. Onset of the myoclonus, continuously presented and intensified by movement and emotional stress, was between the 3rd and 5th decades. Generalized seizures, following worsening of the myoclonus, occurred only a few times in life. This condition was considered to be an autosomal dominant trait with a high rate of penetrance. Although the symptoms gradually worsened with age in some cases, they were not associated with dementia or cerebellar disorder, distinguishing this condition from progressive myoclonus epilepsies (PMEs). Electrophysiologically, polyspikes on the electroencephalogram (EEG), giant wave in somatosensory evoked potentials, enhanced long-loop C reflexes and a preceding wave on jerk-locked back averaging of EEG were demonstrated, suggesting that the myoclonus originated in the cerebral cortices. This is a distinct hereditary disease different from PMEs, juvenile myoclonic epilepsy or other myoclonic disorders seen in adults.
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PMID:Familial benign myoclonus epilepsy of adult onset: a previously unrecognized myoclonic disorder. 907 39

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

Mediterranean myoclonus is a progressive myoclonus epilepsy with autosomal recessive inheritance. Another form has been described in Finland, the so-called Baltic myoclonus. Mediterranean myoclonus and Baltic myoclonus are also known as Unverricht-Lundborg disease. Linkage analyses have shown that the genes for both these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting that they are caused by mutations at the same locus (EPM1). Recently, two heterozygous mutations were found in the cystatin B gene in patients with Unverricht-Lundborg disease. We report recombinational and linkage disequilibrium mapping of EPM1, and cystatin B gene sequencing, in 14 consanguineous pedigrees with Mediterranean myoclonus. Linkage to 21q22.3 DNA markers was observed in all these families. Haplotype analysis suggests that a common mutation segregates within these pedigrees, and that this mutation is different from the common one responsible for the Finnish form of Unverricht-Lundborg disease. No mutation was found in the exons or splice junctions of the cystatin B gene in the 14 pedigrees.
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PMID:Allelic heterogeneity of Mediterranean myoclonus and the cystatin B gene. 915 33

Previously it was reported that some patients with tremor had the same electrophysiological findings as those seen in patients with cortical reflex myoclonus, and consequently the tremor was named "cortical tremor." In the present study, we examined six patients from three families with cortical tremor of relatively late onset. The inheritance pattern of cortical tremor was compatible with autosomal dominant trait. Those patients had relatively rhythmic involuntary movements (tremor) in the distal upper and lower limbs, especially during posture and/or fine movements. There was no cerebellar ataxia or dementia, and fits of loss of consciousness occurred only infrequently. Electrophysiologically, they had generalized spikes on electroencephalogram (EEG), giant cortical components of somatosensory evoked potential, an enhanced long-loop reflex (C-reflex), and cortical spikes preceding the rhythmic jerk demonstrable by the jerk-locked back averaging method, thus fulfilling the criteria of cortical reflex myoclonus. Furthermore, they had slow negative EEG shift starting 1-2 s prior to voluntary movements, suggesting that, as opposed to the conventional form of progressive myoclonus epilepsy (PME), the cerebellar efferent input to the motor cortices was normal. These clinical and electrophysiological pictures are distinct from those of familial essential tremor, familial essential myoclonus, or the conventional form of PME, and the term "familial cortical myoclonic tremor" will represent the clinical and electrophysiological features of this unique entity most appropriately.
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PMID:Familial cortical myoclonic tremor as a unique form of cortical reflex myoclonus. 915 32

We report a 60-year-old woman with progressive ataxia, myoclonus, choreoathetosis, and dementia. She was well until 27 years of the age when she noted an onset of gait disturbance and speech disturbance. She noted abnormal involuntary movements in her four limbs at 42 years of the age. Her symptoms had progressively become worse and she fell down frequently by her 52 years of the age. In addition, her family members noted gradual decline in her intelligence. She was admitted to our hospital in February of 1993 when she was 57-year-old. On admission, she showed dementia, scanning speech, ataxic gait, limb ataxia, action myoclonus, and choreic movements which involved her four limbs. Deep tendon reflexes were slightly exaggerated in the lower limbs; no Babinski sign was noted. Sensation was intact. Laboratory findings were unremarkable. Cerebral MRI revealed atrophy of the cerebellar cortex, superior cerebellar peduncle, brain stem, and the cerebral cortex; the third ventricle and the lateral ventricles were dilated; furthermore, T2-high signal lesions were seen in the cerebral white matter and in the pontine base. Her clinical course was one of the progressive deterioration of her ataxia, involuntary movements, and dementia. She expired on April 24, 1996 when she was 60-year-old. She was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had dentatorubral-pallidoluysian atrophy. A minor opinion was that she might have had myoclonus epilepsy with ragged-red fibers. Postmortem examination revealed atrophy, gliosis, and neuronal loss in the external segment of the globus pallidus, subthalamic nucleus, red nucleus, and in the dentate nucleus. In addition, the gracil and cuneiform nuclei showed neuronal loss and spheroid formation; the spinocerebellar tracts were retained. The substantia nigra and the locus coeruleus were intact. No ragged-red fibers were seen in the muscle biopsy specimen taken in February, 1993. The neuropathologic findings were consistent with the diagnosis of dentatorubral-pallidoluysian atrophy.
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PMID:[(Neurological CPC.55). A 60-year-old woman with progressive cerebellar ataxia, myoclonus, and dementia]. 923 57

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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