Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to assess the efficacy and the safety of ondansetron administered orally in patients with a cerebellar disorder. The study was a randomised, multi-center, double-blind trial. The patients were randomised either to oral ondansetron 8 mg or to placebo twice daily for seven days. Cerebellar dysfunction was quantified before and after treatment using the International Cooperative Ataxia Rating Scale (ICARS). We performed a global analysis (total scores), we analysed by subscores (4 subscores: oculomotor, speech, kinetic, postural) and subgroups (4 subgroups: Cerebellar Cortical Atrophy (CCA), Multiple Systemic Atrophy (MSA), Familial Cerebellar Degeneration (FCD) and miscellaneous cerebellar disorders), and we also performed an analysis by individual test items. We investigated whether ondansetron and placebo had different effects upon ICARS total scores and subscores in the 4 subgroups considered together or separately. For p values < 0.05, we subsequently applied the Mann-Whitney test to compare ondansetron and placebo effect for each individual item. We evaluated 45 of the 46 patients included. No effect was found in global analysis. We found no difference in the analysis of the ICARS subscores. Concerning the individual test items, there was a significant difference between the placebo and ondansetron for the finger-to-nose test (p = 0.049), the Heel-to-Knee test (HK); (p = 0.03), the Body Sway Eyes Closed (p = 0.017) and the Body Sway Eyes Open (BSEO); (p = 0.014). There was no significant difference for tremor in upper limbs (p = 0.32) or for gait (p = 0.49). The Mann-Whitney test showed a greater effect of ondansetron than placebo for BSEO in miscellaneous disorders (p = 0.013) and for HK in FCD (p = 0.036), but ondansetron was deleterious for HK in CCA (p = 0.019). Our study showed no effect of oral ondansetron on global cerebellar dysfunction. The analysis by subgroups showed that the oral form of ondansetron (a) is deleterious for coordination in patients with CCA, (b) has no effect upon tremor in upper limbs, and (c) has a mild effect upon posture and coordination in lower limbs in some subgroups of ataxic diseases.
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PMID:Effects of the oral form of ondansetron on cerebellar dysfunction. A multi-center double-blind study. 1279 31

An 11-year-old boy was evaluated for progressive ataxia, cognitive deterioration, and ophthalmoplegia. The child initially presented with abnormal eye movements at the age of 2 months and was noted to have developmental delay at 6 months. At the age of 7 years, he developed ataxia and cognitive impairment, and subsequently manifested dysphagia and incontinence. The pertinent family history included gait difficulty in the paternal grandmother. At the age of 11, his general physical examination was normal. On neurological examination, he had bilateral external ophthalmoplegia, ataxic dysarthria, dysmetria and tremor in the upper extremities, and marked gait ataxia. An ophthalmological evaluation showed no evidence of pigmentary retinopathy. Brain MRI demonstrated cerebellar, brainstem, and cerebral atrophy. An ataxia panel showed 62 repeats in one allele of the SCA2 gene. Most cases of spinocerebellar ataxia type 2 (SCA2) present between 20 years and 40 years, and affected individuals typically have between 34 and 57 CAG repeats. Neonatal cases of SCA2 have been reported in individuals with over 200 CAG repeats. Childhood SCA2 has been reported previously in two patients but not described clinically. This case broadens the spectrum of the clinical features of infantile-onset SCA2 and highlights the importance of considering this diagnosis in infants and children.
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PMID:Spinocerebellar ataxia type 2 (SCA2) presenting with ophthalmoplegia and developmental delay in infancy. 1473 88

Parkinson's disease is a common neurodegenerative disorder primarily characterized by rigidity, tremor and bradykinesia. Cognitive impairment and neuropsychiatric symptoms are frequent in Parkinson's disease, with a 70% cumulative incidence of dementia. The aim of this cross-sectional study was to establish the pattern of cerebral atrophy on MRI in Parkinson's disease patients with dementia. We used voxel-based morphometry (VBM) to provide an unbiased means of investigating brain volume loss. Whole brain structural T1-weighted MRI scans from Parkinson's disease patients with dementia (PDD, n = 26), Parkinson's disease patients without dementia (n = 31), Alzheimer's disease patients (n = 28), patients with dementia with Lewy bodies (DLB, n = 17) and control subjects (n = 36) were acquired. Images were analysed using SPM99 and the optimized method of VBM. Reduced grey matter volume in PDD patients compared with controls was observed bilaterally in the temporal lobe, including the hippocampus and parahippocampal gyrus, and in the occipital lobe, the right frontal lobe and the left parietal lobe, as well as some subcortical regions. Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects. There was significant grey matter atrophy bilaterally in the occipital lobe of PDD patients compared with Parkinson's disease patients. In addition, significant temporal lobe atrophy, including the hippocampus and parahippocampal gyrus was detected in Alzheimer's disease relative to PDD. No significant volumetric differences were observed in PDD compared with DLB. Thus, Parkinson's disease involves grey matter loss in frontal areas. In PDD, this extends to temporal, occipital and subcortical areas, with occipital atrophy in PDD being the only difference between the two groups. This provides important information about the pattern of cerebral atrophy in Parkinson's disease and PDD.
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PMID:Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. 1474 92

Spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of disorders. Current molecular classification corresponds to the order of gene description (SCA1-SCA 25). The prevalence of SCAs is estimated to be 1-4/100,000. Patients exhibit usually a slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and/or ataxic gait. They can present also with pigmentary retinopathy, extrapyramidal movement disorders (parkinsonism, dyskinesias, dystonia, chorea), pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioral symptoms), peripheral neuropathy. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. The following clinical features have some specific values for predicting a gene defect: slowing of saccades in SCA2, ophthalmoplegia in SCA1, SCA2 and SCA3, pigmentary retinopathy in SCA7, spasticity in SCA3, dyskinesias associated with a mutation in the fibroblast growth factor 14 (FGF 14) gene, cognitive impairment/behavioral symptoms in SCA17 and DRPLA, seizures in SCA10, SCA17 and DRPLA, peripheral neuropathy in SCA1, SCA2, SCA3, SCA4, SCA8, SCA18 and SCA25. Neurophysiological findings are compatible with a dying-back axonopathy and/or a neuronopathy. Three patterns of atrophy can be identified on brain MRI: a pure cerebellar atrophy, a pattern of olivopontocerebellar atrophy, and a pattern of global brain atrophy. A remarkable observation is the presence of dentate nuclei calcifications in SCA20, resulting in a low signal on brain MRI sequences. Several identified mutations correspond to expansions of repeated trinucleotides (CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCA8). A pentanucleotide repeat expansion (ATTCT) is associated with SCA10. Missense mutations have also been found recently. Anticipation is a main feature of SCAs, due to instability of expanded alleles. Anticipation may be particularly prominent in SCA7. It is estimated that extensive genetic testing leads to the identification of the causative gene in about 60-75 % of cases. Our knowledge of the molecular mechanisms of SCAs is rapidly growing, and the development of relevant animal models of SCAs is bringing hope for effective therapies in human.
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PMID:The wide spectrum of spinocerebellar ataxias (SCAs). 1589 52

The fragile X mental retardation 1 gene (FMR1) mutation causes two disorders: fragile X syndrome (FXS) in those with the full mutation and the fragile X-associated tremor/ataxia syndrome (FXTAS) in some older individuals with the premutation. FXS is caused by a deficiency of the FMR1 protein (FMRP) leading to dysregulation of many genes that create a phenotype with ADHD, anxiety, and autism. FXTAS is caused by the elevation of FMR1-mRNA to levels 2 to 8 times normal in the premutation. This causes an RNA gain of function toxicity leading to brain atrophy, white matter disease, neuronal and astrocytic inclusion formation, and subsequent ataxia, intention tremor, peripheral neuropathy, and cognitive decline. The neurobiology and pathophysiology of FXS and FXTAS are described in detail.
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PMID:Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. 1651 73

The association between cerebral small-vessel disease, brain atrophy, and the risk and severity of mild parkinsonian signs (MPS) remains unclear. The objective of this study is to examine the effect of lacunar brain infarcts, cerebral white matter lesions (WMLs), and cortical atrophy on the risk and severity of MPS. This study is a cross-sectional community-based cohort study comprising 268 subjects, 65 to 83 years of age, residing in the Augsburg region of southern Germany, and without contraindications for magnetic resonance imaging (MRI) of the brain. Main outcome measures. Subcortical and periventricular WMLs, lacunar brain infarcts, and cortical atrophy determined using a standardized MRI protocol developed for the Rotterdam Scan Study and an established rating scale. MPS, assessed in a standardized neurological examination and based on the Unified Parkinson's Disease Rating Scale motor scale. Lacunar brain infarcts and large subcortical white matter lesions were associated with an elevated risk of resting tremor. More severe cortical atrophy was related to an increased risk of rigidity and bradykinesia. In a linear regression analysis relating each individual MRI measurement with the severity of MPS, the number of lacunar brain infarcts and the degree of brain atrophy were correlated with the severity of resting tremor, whereas the size of subcortical and periventricular WMLs was correlated with the severity of rigidity. A higher degree of brain atrophy was associated with increased severity of either cardinal sign. In our study, presence and volume of lacunar brain infarcts, cerebral WMLs, and cortical atrophy were associated with the risk as well as severity of MPS. Determining the presence of these brain changes using brain imaging might contribute to identify persons at risk for MPS.
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PMID:Relation of cerebral small-vessel disease and brain atrophy to mild Parkinsonism in the elderly. 1696 Aug 65

Premutation alleles of the fragile X mental retardation 1 (FMR1) gene give rise to a late-onset movement disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by progressive intention tremor and gait ataxia, with associated dementia and global brain atrophy. The natural history of FXTAS is largely unknown. To address this issue, a family-based, retrospective, longitudinal study was conducted with a cohort of 55 male premutation carriers. Analysis of the progression of the major motor signs of FXTAS, tremor and ataxia, shows that tremor usually occurs first, with median onset at approximately 60 years of age. From the onset of the initial motor sign, median delay of onset of ataxia was 2 years; onset of falls, 6 years; dependence on a walking aid, 15 years; and death, 21 years. Preliminary data on life expectancy are variable, with a range from 5 to 25 years.
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PMID:Progression of tremor and ataxia in male carriers of the FMR1 premutation. 1713 2

In Guadeloupe, there is an abnormally high frequency of atypical parkinsonism. Only one-third of the patients that develop parkinsonian symptoms were reported to present the classical features of idiopathic Parkinson disease and one-third a syndrome resembling progressive supranuclear palsy (PSP). The others were unclassifiable, according to established criteria. We carried out a cross-sectional study of 160 parkinsonian patients to: (i) define more precisely the clinical phenotypes of the PSP-like syndrome and the parkinsonism that was considered unclassifiable in comparison with previously known disorders; (ii) define the neuropsychological and brain imaging features of these patients; (iii) evaluate to what extent a candidate aetiological factor, the mitochondrial complex I inhibitor annonacin contained in the fruit and leaves of the tropical plant Annona muricata (soursop) plays a role in the neurological syndrome. Neuropsychological tests and MRI were used to classify the patients into those with Parkinson's disease (31%), Guadeloupean PSP-like syndrome (32%), Guadeloupean parkinsonism-dementia complex (PDC, 31%) and other parkinsonism-related disorders (6%). Patients with a PSP-like syndrome developed levodopa-resistant parkinsonism, associated with early postural instability and supranuclear oculomotor dysfunction. They differed, however, from classical PSP patients by the frequency of tremor (>50%), dysautonomia (50%) and the occurrence of hallucinations (59%). PDC patients had levodopa-resistant parkinsonism associated with frontosubcortical dementia, 52% of these patients had hallucinations, but, importantly, none had oculomotor dysfunction. The pattern of neuropsychological deficits was similar in both subgroups. Cerebral atrophy was seen in the majority of the PSP-like and PDC patients, with enlargement of the third ventricle and marked T2-hypointensity in the basal ganglia, particularly the substantia nigra. Consumption of soursop was significantly greater in both PSP-like and PDC patients than in controls and Parkinson's disease patients. In conclusion, atypical Guadeloupean parkinsonism comprises two forms of parkinsonism and dementia that differ clinically by the presence of oculomotor signs, but have similar cognitive profiles and neuroimaging features, suggesting that they may constitute a single disease entity, and both were similarly exposed to annonaceous neurotoxins, notably annonacin.
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PMID:Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes? 1730 92

Clinical, hematological and cranial neuroimaging findings of eight cases of infantile tremor syndrome are reported. All had coarse tremors, anemia, hyperpigmentation and delayed or regression of developmental milestones. Five patients had microcytic, hypochromic anemia, three had dimorphic anemia. CT scans of two cases and MRI scans of three cases showed cerebral atrophy. One of these two CT scans, in addition, showed a small hypodensity in right basal ganglia region. Two CT scans were normal. One MRI showed hyperintense signals in frontal and periventricular white matter on T2 weighted images. The changes described are non-specific and also seen in cases of malnutrition and viral infections of CNS.
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PMID:Cranial neuroimaging in infantile tremor syndrome (ITS). 1741 98

Fragile X syndrome is the most common form of hereditary mental retardation. The molecular basis of this syndrome is mainly a CGG expansion in the 5' untranslated region of the FMR1 gene. Expansions with more than 200 CGG repeats abolish gene expression causing the classical fragile X phenotype. Premutation carriers (55-200 CGG) have normal cognitive function with increased risk of developing premature ovarian failure and fragile X-associated tremor-ataxia syndrome (FXTAS). Some clinical features associated with FXTAS, such as tremor, gait ataxia, cognitive decline, and generalized brain atrophy, are also seen in other movement disorders. Ninety-five patients referred for HD, who tested negative for the expansion in the IT15 gene, were screened for FMR1 CGG-repeat expansion. One FMR1 premutation male carrier was detected, giving an FXTAS frequency of 1.6%. Our results highlight that FXTAS is still not well diagnosed; therefore, we recommend FMR1 premutation screenings in all patients with late-onset tremor, ataxia, and cognitive dysfunction.
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PMID:Screening for FXTAS in 95 Spanish patients negative for Huntington disease. 1837 10


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