Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was (i) to compare disease progression and survival in different types of degenerative ataxia, and (ii) to identify variables that may modify the rate of disease progression. We included patients suffering from Friedreich's ataxia (FRDA, n = 83), early onset cerebellar ataxia (EOCA, n = 30), autosomal dominant cerebellar ataxia (ADCA) type I (ADCA-I, n = 273), ADCA-III (n = 13) and multiple system atrophy (MSA, n = 67). Molecular genetic testing allowed us to assign 202 ADCA-I patients to one of the following subgroups: spinocerebellar ataxia type I (SCAI, n = 36), SCA2 (n = 56) and SCA3 (n = 110). To assess disease progression we defined the following disease stages: stage 0 = no gait difficulties; stage 1 = disease onset, as defined by onset of gait difficulties; stage 2 = loss of independent gait; stage 3 = confinement to wheelchair; stage 4 = death. Disease progression was most rapid in MSA, intermediate in FRDA, ADCA-I and ADCA-III and slowest in EOCA. The rate of progression was similar in SCA1, SCA2 and SCA3. The CAG repeat length was a significant risk factor for faster progression in SCA2 and SCA3, but not in SCA1. In FRDA, the time until confinement to wheelchair was shorter in patients with earlier disease onset, suggesting that patients with long GAA repeats and early disease onset have a poor prognosis. Female gender increased the risk of becoming dependent on walking aids or a wheelchair, but it did not influence survival in FRDA, SCA3 and MSA. In SCA2, female gender was associated with shortened survival. In MSA, later age of onset increased the risk of rapid progression and death.
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PMID:The natural history of degenerative ataxia: a retrospective study in 466 patients. 957 87

21 patients with diagnosis of idiopathic OPCA were examined clinically and evaluated by MRI or CT-scan. On the basis of Quinn's criteria for MSA, patients were subdivided into those with probable MSA (48 p. cent) and those with possible MSA (52 p. cent). Median age at onset was 51.8 years. The initial clinical feature of the disease was ataxia, but the presence of multiple system involvement was clear in all cases. The combination of involvement of four different system (cerebellar, parkinsonian, pyramidal, autonomic) was the most common (28.5 p. cent), followed by the association of cerebellar and pyramidal features (24 p. cent). Autonomic symptoms were present in 48 p. cent of patients. CY-scan or MRI showed cerebellar and brainstem atrophy in 43 p. cent of cases. There was no relation with the duration of the disease or the severity of clinical features. Moreover brainstem auditory evoked response and EMG were not helpful in diagnosis.
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PMID:[Olivo-ponto-cerebellous degeneration. A study of 21 patients defined by the Quinn criteria]. 968 8

By using three-dimensional magnetic resonance imaging-based volumetry, we studied atrophy of the caudate nucleus, putamen, brainstem, and cerebellum in patients with idiopathic Parkinson's syndrome (IPS, n = 11), progressive supranuclear palsy (PSP, n = 6), and multiple system atrophy with predominant parkinsonism (MSA-P, n = 12) or ataxia (MSA-C, n = 17). Patients were compared with a total of 46 controls, of whom 16 were age matched. Mean striatal, cerebellar, and brainstem volumes were normal in patients with IPS. We found significant reductions in mean striatal and brainstem volumes in patients with MSA-P, MSA-C, and PSP, whereas patients with MSA-C and MSA-P also showed a reduction in cerebellar volume. On an individual basis, volumes of structures in patients with MSA and PSP showed an extensive overlap with the normal range with the exception of brainstem volumes in patients with MSA-C. Therefore, groups could not be discriminated on the basis of individual structure volumetry. Application of stepwise discriminant analysis, however, allowed discrimination of all 12 patients with MSA-P, 15 of 17 patients with MSA-C, and 5 of 6 patients with PSP from the normal and IPS cohorts. However, patients with IPS could not be separated from controls and patients with MSA-P could not be separated from patients with PSP. In conclusion, total intracranial volume-normalized magnetic resonance imaging-based volumetric measurements provide a sensitive marker to discriminate typical and atypical parkinsonism.
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PMID:Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson's syndrome from multiple system atrophy and progressive supranuclear palsy. 989 79

Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 and 12, and the GAA repeat of the frataxin gene in 124 patients apparently suffering from idiopathic sporadic ataxia, including 20 patients with the clinical diagnosis of multiple system atrophy. Patients with a positive family history, a typical Friedreich phenotype, or symptomatic ataxia were excluded. Genetic analyses uncovered the most common Friedreich mutation in 10 patients with an age at onset between 13 and 36 years. The SCA6 mutation was present in nine patients with disease onset between 47 and 68 years of age. The CTG repeat associated with SCA8 was expanded in three patients. One patient had SCA2 attributable to a de novo mutation from a paternally transmitted, intermediate allele. We did not identify the SCA1, SCA3, SCA7 or SCA12 mutation in idiopathic sporadic ataxia patients. No trinucleotide repeat expansion was detected in the MSA subgroup. This study has revealed the genetic basis in 19% of apparently idiopathic ataxia patients. SCA6 is the most frequent mutation in late onset cerebellar ataxia. The frataxin trinucleotide expansion should be investigated in all sporadic ataxia patients with onset before age 40, even when the phenotype is atypical for Friedreich's ataxia.
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PMID:Genetic background of apparently idiopathic sporadic cerebellar ataxia. 1103 Apr 10

We previously have described a group of patients with gluten sensitivity presenting with ataxia (gluten ataxia) and suggested that this disease entity may account for a large number of patients with sporadic idiopathic ataxia. We have therefore investigated the prevalence of gluten sensitivity amongst a large cohort of patients with sporadic and familial ataxia and looked at possible genetic predisposition to gluten sensitivity amongst these groups. Two hundred and twenty-four patients with various causes of ataxia from North Trent (59 familial and/or positive testing for spinocerebellar ataxias 1, 2, 3, 6 and 7, and Friedreich's ataxia, 132 sporadic idiopathic and 33 clinically probable cerebellar variant of multiple system atrophy MSA-C) and 44 patients with sporadic idiopathic ataxia from The Institute of Neurology, London, were screened for the presence of antigliadin antibodies. A total of 1200 volunteers were screened as normal controls. The prevalence of antigliadin antibodies in the familial group was eight out of 59 (14%), 54 out of 132 (41%) in the sporadic idiopathic group, five out of 33 (15%) in the MSA-C group and 149 out of 1200 (12%) in the normal controls. The prevalence in the sporadic idiopathic group from London was 14 out of 44 (32%). The difference in prevalence between the idiopathic sporadic groups and the other groups was highly significant (P < 0.0001 and P < 0.003, respectively). The clinical characteristics of 68 patients with gluten ataxia were as follows: the mean age at onset of the ataxia was 48 years (range 14-81 years) with a mean duration of the ataxia of 9.7 years (range 1-40 years). Ocular signs were observed in 84% and dysarthria in 66%. Upper limb ataxia was evident in 75%, lower limb ataxia in 90% and gait ataxia in 100% of patients. Gastrointestinal symptoms were present in only 13%. MRI revealed atrophy of the cerebellum in 79% and white matter hyperintensities in 19%. Forty-five percent of patients had neurophysiological evidence of a sensorimotor axonal neuropathy. Gluten-sensitive enteropathy was found in 24%. HLA DQ2 was present in 72% of patients. Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia. Antigliadin antibody testing is essential at first presentation of patients with sporadic ataxia.
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PMID:Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. 1293 69

We aimed to develop and validate a novel rating scale for multiple system atrophy (Unified Multiple System Atrophy Rating Scale-UMSARS). The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. For validation purposes, 40 MSA patients were assessed in four centers by 4 raters per center (2 senior and 2 junior raters). The raters applied the UMSARS, as well as a range of other scales, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale (ICARS). Internal consistency was high for both UMSARS-I (Crohnbach's alpha = 0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I and -II subscores was substantial (k(w) = 0.6-0.8) to excellent (k(w) > 0.8). UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the degree of the patient's disability, completion of the entire UMSARS took 30 to 45 minutes. Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients.
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PMID:Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). 1545 68

This study aimed to determine in vivo the atrophy patterns in clinically established cerebellar variant of multiple-system atrophy (MSA-C) using voxel-based morphometry (VBM). Thirteen patients with MSA-C (12 probable, 1 possible) and 13 healthy controls matched for age and sex were included. High-resolution MR images were acquired with a 1.5 T scanner. Images were normalized onto a study-specific template, segmented into the tissue compartments, modulated with the Jacobian determinants, and finally smoothed with a Gaussian kernel filter of 10 mm. The general linear model was used to assess statistical differences in gray and white matter. Infratentorial atrophy was observed in the cerebellar hemispheres, vermis, mesencephalon, and pons of MSA-C patients. Supratentorial volume loss was found in orbitofrontal and mid-frontal regions as well as in temporomesial and insular areas of both hemispheres. A negative correlation was observed between a cerebellar ataxia score and the volume of cerebellar hemispheres, peduncles, and pons. To compare this atrophy pattern to that of spinocerebellar ataxia (SCA2), which was previously reported by our group, a conjunction analysis was assessed. We observed a volume loss shared by both disorders comprising the cerebellum, vermis, pons, mesencephalon, orbitofrontal, mid-frontal, and temporomesial cortex of both hemispheres as well as the left insular cortex.
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PMID:Cortical atrophy in the cerebellar variant of multiple system atrophy: a voxel-based morphometry study. 1616 Oct 39

The North American Multiple System Atrophy Study Group involves investigators in 12 US medical centers funded by a grant from the National Institutes of Health. The objectives are to examine the environmental and genetic risk factors for MSA; elucidate pathogenic mechanisms underlying the disorder; and refine evaluations used for assessment. During its first year, the group enrolled 87 patients, implemented four cores, and initiated four scientific projects. Most patients among the 87 had parkinsonian features, which frequently began asymmetrically and remained asymmetrical; one-third responded to levodopa and many developed levodopa complications; almost two-thirds of the patients had cerebellar dysfunction, of these 90% had ataxia; urinary incontinence occurred commonly, and sleep disorders affected most. The investigators studied the effects of oxidative and nitrative stress upon the formation of alpha-synuclein inclusions; generated transgenic models of alpha-synuclein accumulation that recapitulate several behavioral and neuropathological features of MSA; and compared the severity of the autonomic features of MSA, Parkinson's disease and dementia with Lewy bodies.
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PMID:The North American Multiple System Atrophy Study Group. 1628 10

The cerebellar variant of multiple system atrophy (MSA-C) has overlapping clinical features with the hereditary spinocerebellar ataxias (SCAs), but can usually be distinguished on a clinical basis. We describe a patient who developed a sporadic, late-onset, rapidly progressive neurodegenerative disorder consistent with MSA-C. Genetic testing, however, showed an abnormal expansion of one allele of the spinocerebellar ataxia 3 (SCA3) gene. The clinical impression of MSA-C was confirmed by identification of numerous alpha-synuclein-containing glial cytoplasmic inclusions on autopsy. These findings suggest that abnormal expansion of the SCA3 gene may be a risk factor for the development of MSA-C.
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PMID:Multiple system atrophy in a patient with the spinocerebellar ataxia 3 gene mutation. 1713 18

To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.
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PMID:PET study of brain acetylcholinesterase in cerebellar degenerative disorders. 1841 83


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