Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with a heterogeneous clinical picture characterized by the presence of eosinophilic intranuclear inclusions in neuronal and glial cells. We describe a case, reported 12 years ago as dopa-responsive dystonia (DRD) with Lewy body pathology. Pathological re-examination has led to a revised diagnosis of neuronal intranuclear inclusion disease. This rare condition, which may be diagnosed in life with a full thickness rectal biopsy, needs to be considered in the differential diagnosis of any case presenting as progressive juvenile parkinsonism (JP) or dystonia.
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PMID:Neuronal intranuclear inclusion disease: report on a case originally diagnosed as dopa-responsive dystonia with Lewy bodies. 1596 5

Early onset torsion dystonia (DYT1), the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein, torsinA. We previously examined the effect of the human mutant torsinA on striatal dopaminergic function in a conventional transgenic mouse model of DYT1 dystonia (hMT1), in which human mutant torsinA is expressed under the cytomegalovirus promotor. Systemic administration of amphetamine did not increase dopamine (DA) release as efficiently in these mice as compared with wild-type transgenic and non-transgenic mice. We, now, studied the contribution of the DA transporter (DAT) to amphetamine-induced DA release in hMT1 transgenic mice using in vivo no-net flux microdialysis. This method applies different concentrations of DA through the microdialysis probe and measures DA concentration at the output of the probe following an equilibrium period. The slope (extraction fraction) is the measure of the DAT activity in vivo. The slope for hMT1 transgenic mice was 0.58 +/- 0.07 and for non-transgenic animals, 0.87 +/- 0.06 (p < 0.05). We further investigated the efficacy of nomifensine (a specific DAT inhibitor) in inhibiting amphetamine-induced DA release. Local application of nomifensine 80 min before the systemic application of amphetamine inhibited DA release in both transgenic mice and their non-transgenic littermates. The efficiency of the inhibition appeared to be different, with mean values of 48% for hMT1 transgenic mice versus 84% for non-transgenic littermates. Moreover, we have evaluated basal and amphetamine-induced locomotion in hMT1 transgenic mice compared with their non-transgenic littermates, using an O-maze behavioral chamber. Basal levels of locomotion in the hMT1 transgenic mice showed that they moved much less than their non-transgenic littermates (0.9 +/- 0.3 m for transgenic mice vs. 2.4 +/- 0.7 m for non-transgenic littermates, p < 0.05). This relative reduction in locomotion was also observed following amphetamine administration (48.5 +/- 6.7 m for transgenics vs. 73.7 +/- 9.8 m for non-transgenics, p < 0.05). These results support the finding that there are altered dynamics of DA release and reuptake in hMT1 transgenic mice in vivo, with DAT activity is reduced in the presence of mutant torsinA, which is consistent with behavioral consequences such as reduced locomotion and (previously described) abnormal motor phenotypes such as increased hind-base width and impaired performance on the raised-beam task. These data implies that altered DAT function may contribute to impaired DA neurotransmission and clinical symptoms in human DYT1 dystonia.
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PMID:Function of dopamine transporter is compromised in DYT1 transgenic animal model in vivo. 2013 87

A 29-year-old immunocompetent woman was admitted in 2006 with ataxia, limb weakness, generalized dystonia, and vertical diplopia that developed after a febrile episode. Brain magnetic resonance imaging (MRI) revealed the presence of extensive periventricular white matter lesions that did not enhance after gadolinium injection. As low titers of cytomegalovirus-IgM antibodies were found in the serum, a presumed diagnosis of postviral acute disseminated encephalomyelitis (ADEM) was made, and the patient received a 5-day course of 1 g methylprednisolone. The clinical and radiological outcome was very rapidly favorable, and subsequent brain MRIs in 2007 and 2008 were normal. In March 2011, the patient was readmitted with the complaints of abnormal fatigue, imbalance, and speech disorder. The neurological examination showed fluctuating spatiotemporal disorientation with dyscalculia, verbal deafness, gait ataxia, right hemianopia, and pyramidal signs in the four limbs. The brain MRI demonstrated extensive T(2) hyperintense white matter lesions predominating in the left temporal and parieto-occipital lobes, with a pseudotumoral aspect enhancing with gadolinium contrast. A clinical improvement was transiently noted after pulse steroid therapy, but after relapse and radiological worsening, the diagnosis of recurrent ADEM was challenged. The brain biopsy confirmed the presence of primary central nervous system lymphoma (PCNSL) under the variant form of lymphomatosis cerebri. Despite a partial response to chemotherapy, the patient died 8 months after the diagnosis. We discuss the role of sentinel lesions that may precede PCNSL for several years and insist on the importance to consider early brain biopsy in the presence of extensive, non-enhancing white matter lesions, even in a young and immunocompetent patient.
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PMID:Lymphomatosis cerebri Presenting as a Recurrent Leukoencephalopathy. 2318 72

Neuronal intranuclear inclusion disease is a rare, neurodegenerative disorder with onset in childhood. We report a single case natural history over 10 years and present a review of juvenile parkinsonism and neuronal intranuclear inclusion disease. Our patient was initially seen at the University of Rochester at age 12 years after 4 years of progressive dysarthria, dysphagia, and clumsiness. His neurologic examination was notable for parkinsonism. He had excellent initial response to levodopa, but subsequently developed dopa-induced motor fluctuations, dyskinesias, psychosis, and dystonia. Later in the course, he developed multiple nonmotor symptoms and ultimately died from respiratory failure. Neuropathology demonstrated large eosinophilic nuclear inclusions and small ubiquitin-related modifier 1 (SUMO-1) immunoreactivity, confirming the diagnosis of neuronal intranuclear inclusion disease. This diagnosis should be considered in a patient presenting with juvenile parkinsonism. Clues to the diagnosis include early-onset dopa-induced dyskinesias, gastrointestinal dysfunction, and oculogyric crises.
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PMID:Neuronal Intranuclear Inclusion Disease: Longitudinal Case Report of Motor and Nonmotor Symptoms. 3130 25