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)

In Papio papio baboons benzodiazepines can facilitate the appearance of a naturally occurring non-epileptic myoclonus, suggesting a possible role of GABAergic transmission in their physiopathology. Nevertheless, as this myoclonus is blocked by physostigmine, the effect of benzodiazepines is probably due to their indirect action on the cholinergic system. Therefore, in this study, we report the effects on the non-epileptic myoclonus of drugs influencing GABAergic transmission. Systemic injections of progabide (GABA precursor), baclofen (GABAB receptor agonist) and allylglycine (glutamic acid decarboxylase inhibitor) did not modify or induce the non-epileptic myoclonus. In the same way, localized chronic injections of GABA into various cerebral structures (prefrontal and motor cortical areas, reticular magnocellular nucleus and substantia nigra) had no effect. When the two types of myoclonus were present in the same photosensitive animal, the epileptic myoclonus induced by photic stimulation was blocked by benzodiazepines but was not influenced by physostigmine, thus differing from the non-epileptic myoclonus. This suggests that different neurochemical mechanisms are involved in the two types of myoclonus, the non-epileptic myoclonus not being directly influenced by the GABAergic transmission.
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PMID:Drugs influencing the GABAergic neurotransmission have no effect on the non-epileptic myoclonus of baboons. 171 29

The specific activities of glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) were measured in 6 regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. These rats exhibited signs of neurological impairment which included visual deficits, ataxia, spasticity and myoclonus. At the onset of neurological impairment, there was a significant reduction in GAD activity in the occipital cortex (43%), frontal cortex (37%) and caudate-putamen (42%). Preceding the onset of neurological impairment, diminished GAD activity was detected only in the occipital cortex. In the cerebellum, thalamus and spinal cord, GAD activities were normal throughout the experiment. No significant differences in ChAT activity were detected in any of the 6 regions. These results are consistent with a preferential involvement of GABAergic neurons in methylmercury-induced lesions of the cerebral cortex and neostriatum.
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PMID:Methylmercury poisoning of the developing nervous system in the rat: decreased activity of glutamic acid decarboxylase in cerebral cortex and neostriatum. 404 11

This study was designed to investigate the effect of T. serrulatus scorpion venom on dopamine (DA) and gamma amino butyric acid (GABA) concentrations in different regions of the brain. The ratio of homovanillic acid (HVA) to DA, and the glutamic acid decarboxylase (GAD) activity were determined following intravenous or intracerebral venom injections. The increase in the HVA/DA ratio in the striatum after i.v. or intrastriatal injection could indicate an increase in DA turnover. One hour after i.v. injection of the venom GAD activity was shown to be decreased in the striatum and hypothalamus. After 24 hr GAD activity increased in the striatum and decreased in the hypothalamus and brain stem. These results could indicate different effects of the venom on the GABA system in different areas of the brain. After intrastriatal injection of the scorpion venom, the animals showed stereotyped behavior and rotation activity. Following intrahippocampal injection, myoclonus and orofacial automatisms, which constitute pro-convulsive signals, were observed. These behavioral alterations could be, at least in part, related to the GABA and dopamine alterations caused by the venom, since stereotypy, circling behavior and convulsions are dependent on dopamine and/or GABA.
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PMID:Effects of Tityus serrulatus crude venom on the GABAergic and dopaminergic systems of the rat brain. 772 31

The neurophysiological findings in eight patients with the stiff man syndrome (SMS), including four of six tested with autoantibodies against glutamic acid decarboxylase, are presented. Neurophysiological findings did not make it possible to discriminate between patients with and those without autoimmunity against GABAergic neurons. Investigation of mono- and polysynaptic reflexes revealed abnormal results in a variable number of SMS patients, the abnormalities largely corresponding to those seen in spastic paresis. A stereotyped motor response to electrical stimulation of peripheral nerves was recorded from the trunk muscles of all patients investigated. This response was termed spasmodic reflex myoclonus and consisted of a sequence of 1-3 synchronous myoclonic bursts, 60-70 ms after median nerve stimulation, followed by a tonic decrescendo activity over a number of seconds. The recruitment order of muscles along the neuraxis in spasmodic reflex myoclonus suggested that the latter was generated in the spinal cord and conveyed via propriospinal tracts. It is thought that spasmodic reflex myoclonus may serve not only as a diagnostic tool, but also as a key to understanding some aspects of the pathophysiology of both spasms and stiffness in SMS. It is speculated that stiffness is a fragment of spasms, both being generated by common neuronal mechanisms tentatively ascribed to interneurons in the spinal grey matter.
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PMID:Stiff man syndrome: neurophysiological findings in eight patients. 883 47

We report the presence of serum autoantibodies directed against glutamic acid decarboxylase in a patient with epilepsy and palatal myoclonus not associated with brain lesions. Glutamic acid decarboxylase antibody reactivity was dependent on the presence of carboxy-terminal amino acids, similar to that reported in patients with stiff-man syndrome. Marked reduction in the frequency of epileptic attacks and improvement in palatal myoclonus occurred when benzodiazepine was administered and phenytoin was gradually tapered. Testing for anti-glutamic acid decarboxylase antibodies may be indicated in patients with palatal myoclonus and with convulsive disorders refractory to therapy.
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PMID:Autoantibodies to glutamic acid decarboxylase in palatal myoclonus and epilepsy. 765 81

The clinical, biochemical, neuroimaging and neurophysiological findings of eight patients with stiff man syndromes (SMS) [four of six being tested with autoantibodies against glutamic acid decarboxylase (GAD)] are presented. In two patients (one GAD-positive, one GAD-negative), transient oculomotor disturbances suggested progressive encephalomyelitis with rigidity and myoclonus (PERM) as differential diagnosis. The catalogue of characteristic clinical symptoms of SMS is extended by three new symptoms: (1) an aura-like feeling reported by five patients to precede spontaneous spasmodic attacks; (2) a stereotyped motor pattern seen in seven patients during spasmodic jerks, consisting of brief opisthotonos, stiffening of the slightly abducted legs and inversion of the plantar-flexed feet; (3) a paroxysmal fear when crossing a free space unaided, or even thinking of it. Clinical findings did not enable us to discriminate between patients tested GAD-positive or GAD-negative. Cerebrospinal fluid contained elevated immunoglobulin levels or cell counts, or both, in the majority of patients. Autopsy of one patient revealed scattered lymphocyte cuffs around leptomeningeal, intracerebral and particularly intraspinal vessels, suggesting a mild inflammatory process. Whether SMS and PERM are closely related is discussed; they are possibly both manifestations of a spectrum of encephalomyelopathies having autoimmunity against GABAergic neurons in common.
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PMID:Stiff man syndrome: clinical and laboratory findings in eight patients. 2154 85

Little is known about the pathogenetic basis of characteristic symptoms in transmissible spongiform encephalopathies (TSEs) such as myoclonus and characteristic EEG hyperactivity. We investigated the GABAergic system and its subpopulations in mice inoculated with experimental scrapie (ME7, RML, 22A strains) and Creutzfeldt-Jakob disease (CJD; Fujisaki strain), to study damage to inhibitory neurons. Since recent studies have shown electrophysiological changes in prion protein (PrP) knockout mice, we also studied mice lacking or overexpressing the PrP gene. Antibodies against glutamic acid decarboxylase (GAD), parvalbumin (PV), calbindin (CB), and calretinin (CR) were used to stain GABAergic neurons, and isolectin-B4 to stain perineuronal nets around PV+ neurons. In scrapie infected mice, cortical PV+ neurons were severely reduced while CB+ and CR+ neurons were well preserved. In CJD inoculated mice, loss of PV+ neurons was severe and occurred very early after inoculation. PrP-/- and tg20 mice showed normal appearance of PV, CB, CR, GAD+ neurons and their neuropil, and of isolectin-B4+ perineuronal nets. The early, severe and selective loss of cortical PV+ neurons in experimental scrapie and CJD suggest selective loss of PV+ GABAergic neurons as important event during disease development, possibly as one basis of excitatory symptoms in TSEs.
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PMID:Severe, early and selective loss of a subpopulation of GABAergic inhibitory neurons in experimental transmissible spongiform encephalopathies. 980 71

Rigidity in the setting of continuous motor unit activity at rest can be caused by a variety of central and peripheral conditions. A central origin is suggested by the presence of painful reflex spasms. Focal spinal lesions and infective causes are relatively easily excluded through imaging, microbiological and serological studies. There then remain a group of patients who may have the classical 'stiff-man syndrome' or a related syndrome. When strict diagnostic criteria are used, patients with the stiff man syndrome uniformly have axial rigidity, and about 90% are found to have antibodies against glutamic acid decarboxylase. Treatment response and prognosis are excellent. Stiff persons with 'plus' signs, particularly those with rigidity of a distal limb, are unlikely to have the classical stiff man syndrome. They have a poorer treatment response and prognosis. Some have a paraneoplastic aetiology, while a non-malignant autoimmune basis seems likely in others. Those in whom post-mortem pathology findings are available usually are seen to have had an encephalomyelitis with prominent involvement of the grey matter. Clinically, stiff persons with 'plus' signs may be divided into three groups according to the aggressiveness of the pathology and its relative distribution. Encephalomyelitis with rigidity follows a relentless subacute course, leading to death within 3 years. Chronic cases may present with predominantly brainstem involvement, including generalised myoclonus (the 'jerking stiff person syndrome') or spinal cord involvement, dominated by stiffness and spasm in one or more limbs (the 'stiff limb syndrome').
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PMID:The stiff man and stiff man plus syndromes. 1046 Apr 39

We analysed a series of 24 adult patients with idiopathic (10 cases) and paraneoplastic (14 cases) opsoclonus-myoclonus syndrome (OMS) to ascertain possible differences in clinical course and response to immunotherapies between both groups. Associated tumours were small-cell lung cancer (SCLC) (nine patients), non-SCLC (one patient), breast carcinoma (two patients), gastric adenocarcinoma (one patient) and kidney carcinoma (one patient). Patients with paraneoplastic OMS were older [median age: 66 years versus 40 years (P = 0.006) of those with idiopathic OMS] and had a higher frequency of encephalopathy (64% versus 10%; P = 0.02). Serum from 10/10 idiopathic and 12/14 paraneoplastic OMS patients showed no specific immunoreactivity on rat or human brainstem or cerebellum, lacked specific antineuronal antibodies (Hu, Yo, Ri, Tr, glutamic acid decarboxylase, amphiphysin or CV2) and did not contain antibodies to voltage-gated calcium channels. The two paraneoplastic exceptions were a patient with SCLC, whose serum contained both anti-Hu and anti-amphiphysin antibodies and a patient with breast cancer who had serum anti-Ri antibodies. The clinical course of idiopathic OMS was monophasic except in two elderly women who had relapses of the opsoclonus and mild residual ataxia. Most idiopathic OMS patients made a good recovery, but residual gait ataxia tended to persist in older patients. Immunotherapy (mainly intravenous immunoglobulins or corticosteroids) seemed to accelerate recovery. Paraneoplastic OMS had a more severe clinical course, despite treatment with intravenous immunoglobulins or corticosteroids, and was the cause of death in five patients whose tumours were not treated. By contrast the eight patients whose tumours were treated showed a complete or partial neurological recovery. We conclude that idiopathic OMS occurs in younger patients, the clinical evolution is more benign and the effect of immunotherapy appears more effective than in paraneoplastic OMS. In patients aged 50 years and older with OMS who develop encephalopathy, early diagnosis and treatment of a probable underlying tumour, usually SCLC, is indicated to increase the chances of neurological recovery. At present, there are no immunological markers to identify the adult patients with paraneoplastic OMS.
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PMID:Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. 1115 70

Stiff man syndrome (SMS), an uncommon neurological disease, is characterised by symmetrical muscle stiffness and spasms that often lead to skeletal deformity. Variants of the syndrome may involve one limb only (stiff leg syndrome), a variety of additional neurological symptoms and signs such as eye movement disturbances, ataxia, or Babinski signs (progressive encephalomyelitis with rigidity and myoclonus), or be associated with malignant disease (paraneoplastic SMS). Antineuronal autoimmunity and accompanying autoimmune diseases, most often insulin-dependent diabetes mellitus, are characteristic features of SMS and its variants. The condition is frequently misinterpreted as psychogenic movement disturbance, but electromyographic abnormalities and the presence of autoantibodies against glutamic acid decarboxylase (GAD) in both serum and cerebrospinal fluid help to establish the correct diagnosis. The aetiology of SMS is obscure. However, several features suggest that SMS is an autoimmune-mediated chronic encephalomyelitis. In line with this hypothesis, immunomodulation with a front-loaded methylprednisolone regimen reduces stiffness and spasms and improves other neurological symptoms in the majority of patients. Plasmapheresis or intravenous immunoglobulins are effective less frequently. For symptomatic treatment, the benzodiazepines are drugs of first choice. An alternative of last resort is baclofen administered intrathecally via an implanted pump device.
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PMID:Stiff man syndrome. 1151 Jun 22


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