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)

On the French West Indian island of Guadeloupe, atypical parkinsonian patients represent two-thirds of all cases of parkinsonism, which is exceptionally frequent compared to epidemiological data from European countries where atypical parkinsonism accounts for only approximately 5% of all cases. The clinical entity was a unique combination of levodopa-resistant parkinsonism, tremor, myoclonus, hallucinations, REM sleep behavior disorder and fronto-subcortical dementia. Based on the presence or the absence of supranuclear gaze palsy, two subgroups of patients were distinguished. In patients with oculomotor signs that came to autopsy, neuronal loss was found to predominate in the substantia nigra and the striatum but other brain areas were also affected, including the frontal cortex. In addition, tau-containing lesions were detected throughout the brain. Epidemiological data suggested a close association of the disease with the regular consumption of soursop, a tropical annonaceous plant. Experimental studies performed in midbrain cell cultures identified annonacin, a selective mitochondrial complex I inhibitor contained in the fruit and leaves of soursop, as a probable etiological factor. Consistent with this view, chronic administration of annonacin to rats through Alzet osmotic minipumps showed that annonacin was able to reproduce the brain lesions characteristic of the human disease.
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PMID:Atypical parkinsonism in the Caribbean island of Guadeloupe: etiological role of the mitochondrial complex I inhibitor annonacin. 1881 93

We determined plasma amantadine concentrations in patients with Parkinson's disease (PD) in daily clinical practice and investigated the relationship between plasma concentration and adverse reactions to clarify the safe therapeutic range. Seventy-eight consecutive PD patients on stable amantadine treatment were recruited. Plasma concentration of amantadine was measured 3h after the administration of morning amantadine dose. Serum creatinine was measured to estimate renal function. The mean daily dose of amantadine was 135.1+/-62.3mg/day, and the mean plasma amantadine concentration was 812.5+/-839.5 ng/ml (range, 91-4400 ng/ml). Plasma amantadine concentration increased according to increasing renal dysfunction. Three patients exhibited adverse reactions, such as myoclonus, hallucinations, and delirium, and all of them showed plasma amantadine concentration >3000 ng/ml. None of the three cases had previously shown such side effects. PD patients who have not developed any psychiatric symptoms as adverse reactions to the treatment may develop myoclonus, hallucination, or delirium when the plasma concentration of amantadine exceeds 3000 ng/ml. It is therefore recommended to use amantadine at the plasma concentration of less than 3000 ng/ml in the treatment of Parkinson's disease, especially in elderly patients.
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PMID:Plasma amantadine concentrations in patients with Parkinson's disease. 1882 13

Atypical parkinsonism is extremely frequent in Guadeloupe and may have an environmental cause. One-half of the patients with this tauopathy have dopa-resistant parkinsonism, tremor, subcortical dementia and abnormal eye movements suggestive of progressive supranuclear palsy (PSP). They also have hallucinations, dysautonomia, which are not characteristic of PSP. Furthermore, the oculomotor abnormalities and the tremor, which is jerky, differ from what is observed in classical PSP patients. We therefore undertook an electrophysiological study to characterize these features in greater detail. Nine representative Guadeloupean PSP-like (Gd-PSP) patients were selected for electro-oculographic recordings of horizontal eye movements [visually guided saccades (VGS), antisaccades (AS) and smooth pursuit], clinical evaluation of vertical saccade velocity and electrophysiological analysis of abnormal limb movements [electromyographic polygraphy, EEG jerk-locked-back-averaging (JLBA) and long-loop C-reflex]. Vertical saccade velocity was reduced in five patients. The velocity of horizontal VGS was normal, although the latencies were increased and horizontal smooth pursuit (HSP) was mostly saccadic. The AS error rate was above 70% in most patients. Myoclonus was detected in 89% of the Gd-PSP patients. It was mainly small amplitude rest and action myoclonus in the upper limbs, characterized by short arrhythmic 24-76 ms bursts and was of cortical origin, as confirmed by JLBA in five patients. In conclusion, Gd-PSP patients have cortical myoclonus and cortical oculomotor impairments, but only minor signs of brainstem oculomotor dysfunction, suggesting that cortical dysfunction predominates over brainstem impairments. This electrophysiological study, added to previous clinical, neuropsychological and neuroradiological studies, has enriched the characterization of Guadeloupean atypical parkinsonism, which thus appears to be a new clinical entity.
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PMID:Predominant cortical dysfunction in Guadeloupean parkinsonism. 1894 Nov 45

Lafora disease (LD) is an autosomal recessive and fatal form of progressive myoclonus epilepsy. LD patients manifest myoclonus and tonic-clonic seizures, visual hallucinations, and progressive neurologic deterioration beginning at 12 to 15 years of age. The two genes known to be associated with LD are EPM2A and NHLRC1. Mutations in at least one other as yet unknown gene also cause LD. The EMP2A encodes a protein phosphatase and NHLRC1 encodes an ubiquitin ligase. These two proteins interact with each other and, as a complex, are thought to regulate critical neuronal functions. Nearly 100 distinct mutations have been discovered in the two genes in over 200 independent LD families. Nearly half of them are missense mutations, and the deletion mutations account for one-quarter. Several reports have provided functional data for the mutant proteins and a few also provide genotype-phenotype correlations. In this review we provide an update on the spectrum of EPM2A and NHLRC1 mutations, and discuss their distribution in the patient population, genotype-phenotype correlations, and on the possible effect of disease mutations on the cellular functions of LD proteins.
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PMID:Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes. 1926 91

The literature is reviewed. Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with Hashimoto thyroiditis (SREHT). The incidence of SREHT in childhood is underestimated. Two subtypes have been described. The diffuse progressive type is associated with insidious onset and progressive impairment of mental status, such as confusion, somnolence, and psychosis. The vasculitic type is characterized by acute stroke-like episodes associated with focal neurologic features and seizures. Hashimoto encephalopathy (SREHT) is a clinical condition with elevated thyroid antibody titers encompassing persistent or relapsing seizures, myoclonus, focal neurologic deficits and neuropsychiatric disorders such as psychosis, delusions and hallucinations, and affective disorders. By far, the vast majority of reports on paediatric and adult patients describe a dramatic clinical response to either methylprednisolone pulse therapy or daily oral prednisone or prednisolone.
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PMID:[Undetected Hashimoto encephalopathy--a diagnostic challenge in child psychiatry and child neurology]. 2004 73

In the Caribbean island of Guadeloupe, patients with atypical parkinsonism develop a progressive supranuclear palsy-like syndrome, named Guadeloupean parkinsonism. Unlike the classical forms of progressive supranuclear palsy, they develop hallucinations and myoclonus. As lesions associated with Guadeloupean parkinsonism are poorly characterized, it is not known to what extent they differ from progressive supranuclear palsy. The aim of the present study was to determine the structural and metabolic profiles of Guadeloupean parkinsonism compared with progressive supranuclear palsy and controls using combined structural and diffusion magnetic resonance imaging and magnetic resonance spectroscopy. We included 9 patients with Guadeloupean parkinsonism, 10 with progressive supranuclear palsy and 9 age-matched controls. Magnetic resonance imaging examination was performed at 1.5 T and included 3D T(1)-weighted and fluid-attenuated inversion recovery images, diffusion tensor imaging and single voxel magnetic resonance spectroscopy in the lenticular nucleus. Images were analysed using voxel-based morphometry, voxel-based diffusion tensor imaging and brainstem region of interest measurements. In patients with Guadeloupean parkinsonism, structural and diffusion changes predominated in the temporal and occipital lobes, the limbic areas (medial temporal, orbitofrontal and cingulate cortices) and the cerebellum. In contrast to patients with progressive supranuclear palsy, structural changes predominated in the midbrain and the basal ganglia and diffusion abnormalities predominated in the frontocentral white matter, the basal ganglia and the brainstem. Compared with controls, the N-acetylaspartate to creatinine ratio was decreased in patients with progressive supranuclear palsy and to a lesser extent in patients with Guadeloupean parkinsonism. The pattern of structural and diffusion abnormalities differed between progressive supranuclear palsy and Guadeloupean parkinsonism. Widespread cortical atrophy was observed in patients with Guadeloupean parkinsonism who presented marked cognitive changes and hallucinations, whereas midbrain lesions were less severe than in progressive supranuclear palsy. Midbrain (progressive supranuclear palsy) or cortical (Guadeloupean parkinsonism) atrophy was a distinctive neuroimaging feature for differential diagnosis.
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PMID:Magnetic resonance imaging lesion pattern in Guadeloupean parkinsonism is distinct from progressive supranuclear palsy. 2082 34

Lafora disease is a fatal autosomal recessive form of progressive myoclonus epilepsy. Patients manifest myoclonus and tonic-clonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence. The two genes known to be involved in Lafora disease are EPM2A and NHLRC1 (EPM2B). The EPM2A gene encodes laforin, a dual-specificity protein phosphatase, and the NHLRC1 gene encodes malin, an E3-ubiquitin ligase. The two proteins interact with each other and, as a complex, are thought to regulate glycogen synthesis. Here, we report three Lafora families with two novel pathogenic mutations (C46Y and L261P) and two recurrent mutations (P69A and D146N) in NHLRC1. Investigation of their functional consequences in cultured mammalian cells revealed that malin(C46Y), malin(P69A), malin(D146N), and malin(L261P) mutants failed to downregulate the level of R5/PTG, a regulatory subunit of protein phosphatase 1 involved in glycogen synthesis. Abnormal accumulation of intracellular glycogen was observed with all malin mutants, reminiscent of the polyglucosan inclusions (Lafora bodies) present in patients with Lafora disease.
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PMID:Lafora progressive myoclonus epilepsy: NHLRC1 mutations affect glycogen metabolism. 2150 99

Lafora disease (LD) is a fatal autosomal recessive form of progressive myoclonus epilepsy. Patients manifest myoclonus and tonic-clonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence. The two genes known to be involved in Lafora disease are EPM2A and NHLRC1 (EPM2B). The EPM2A gene encodes laforin, a dual-specificity protein phosphatase, and the NHLRC1 gene encodes malin, an E3-ubiquitin ligase. The two proteins interact with each other and, as a complex, are thought to regulate glycogen synthesis. It may also be considered as a disorder of carbohydrate metabolism because of the formation of polyglucosan inclusion bodies in neural and other tissues due to abnormalities of the proteins laforin or malin. The review also outlines important patents related to Lafora disease.
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PMID:Lafora progressive myoclonus epilepsy: recent insights into cell degeneration. 2236 17

Morvan syndrome is characterized by central, autonomic, and peripheral hyperactivity. Examples of central hyperactivity include confusion, memory problems, hallucinations, insomnia, and myoclonus; examples of autonomic hyperactivity include hyperhidrosis and fluctuations in blood pressure; examples of peripheral hyperreactivity include clinical or electrophysiological evidence of painful cramps, myokymia, and neuromyotonia. We present a typical case of Morvan syndrome and the first detailed review of the clinical and therapeutic literature of all 27 cases from the English language literature. Morvan syndrome is considered to be an autoimmune disorder and antibodies against voltage-gated potassium channels are found in most cases. Oral immunomodulatory therapy, intravenous immunoglobulin, and plasmapharesis may be entertained. Thymoma is found in approximately 50% of cases and thymectomy may be curative as in our particular case.
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PMID:Morvan syndrome: a case report and review of the literature. 2262 67

The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht-Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and causes translocation of the two proteins to the nucleus. We find that Phe261Leu-PRDM8 results in excessive sequestration of laforin and malin in the nucleus and that it therefore likely represents a gain-of-function mutation that leads to an effective deficiency of cytoplasmic laforin and malin. We have identified a new progressive myoclonus epilepsy with Lafora bodies, early-onset Lafora body disease, 101 years after Lafora disease was first described. The results to date suggest that PRDM8, the early-onset Lafora body disease protein, regulates the cytoplasmic quantities of the Lafora disease enzymes.
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PMID:Early-onset Lafora body disease. 2296 47


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