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)

Because the transverse pontine fibres degenerate in some subtypes of spinocerebellar degeneration (SCD), demonstration of these fibres may be helpful for radiological diagnosis of SCD. Using multishot diffusion-weighted MRI, we attempted to find a way to show the transverse pontine fibres. We assessed the quality of demonstration of these fibres on DWI and of abnormal high signal in the pons and middle cerebellar peduncles on T2-weighted images. We examined evaluated 24 control subjects and 12 patients with SCD: two with sporadic olivopontocerebellar atrophy (OPCA), five with spinocerebellar ataxia type 1 (SCA1), two with SCA3, and three with SCA6. In all control subjects and patients with SCA6, we succeeded in demonstrating the transverse pontine fibres as clear low-signal bundles using DWI. In two patients with SCA3, these fibres were identified less distinctly. In contrast, in two patients with sporadic OPCA and in four of five patients with SCA1, the fibres were not identified. In both patients with sporadic OPCA, abnormal high-signal foci were seen in the base of the pons and middle cerebellar peduncles on T2-weighted images; no such foci were detected in any patient with SCA1, SCA3 or SCA6. DWI seems to be useful for demonstrating transverse pontine fibres. Abnormal high signal in the pons and middle cerebellar peduncles may provide a clue to differentiation of sporadic OPCA from other types of SCD.
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PMID:Diffusion- and T2-weighted MRI of the transverse pontine fibres in spinocerebellar degeneration. 1115 84

To identify the prevalence and determinants of restless legs syndrome (RLS) in spinocerebellar ataxia (SCA) we studied 58 patients with a molecular diagnosis of SCA1, SCA2 and SCA3. Data on the symptoms of RLS were collected by a standardized questionnaire, and RLS was diagnosed when patients met the four minimal criteria of the syndrome as recently defined by an international study group. In addition, we studied the relationship between RLS and age, age at ataxia onset, CAG repeat length, and nerve conduction and evoked potentials data. RLS was significantly more frequent in SCA patients than in controls (28% vs. 10%). Age at RLS onset in SCA was 49.0 +/- 10.9 years. There were no significant differences in nerve conduction or evoked potentials between RLS and non-RLS SCA patients. The probability of developing RLS increased with age but not with CAG repeat length or higher age of ataxia onset. The data provide evidence that patients with SCA1, SCA2 and SCA3 are per se more susceptible to RLS than non-affected individuals. The probability of developing RLS is related principally to the period over which the CAG repeat mutation exerts its effect and not to CAG repeat length or age of ataxia onset.
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PMID:Restless legs syndrome in spinocerebellar ataxia types 1, 2, and 3. 1137 96

We previously verified the effectiveness of tetrahydrobiopterin (BH4) on the ataxia in Machado-Joseph disease (MJD; SCA3 [spinocerebellar ataxia type 3]) as one of the most common types of dominantly inherited spinocerebellar ataxias. We hypothesized as to the pharmacological mechanism of BH4 that on the basis of 'cerebellar long-term depression' theory, BH4 may exert its actions at the levels of soluble guanylate cyclase in the Purkinje cells and of nitric oxide synthase in the granule cells. If cerebellar long-term depression is the case as the theoretical basis of BH4, it will open a new page of therapeutic strategy for spinocerebellar ataxias.
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PMID:Effects of tetrahydrobiopterin on ataxia in Machado-Joseph disease may be based upon the theory of 'cerebellar long-term depression'. 1146 Nov 69

Neuronal intranuclear inclusions (NIIs) found in CAG/polyglutamine-expansion disorders contain both expanded polyglutamine and the gene product without the CAG repeat. The gene product containing expanded polyglutamine has, therefore, been considered to be a major component of NIIs. In this immunohistochemical study, we showed recruitment of ataxin-2, ataxin-3 and TATA box binding protein (TBP) into NIIs of the pontine neurons of spinocerebellar ataxia type (SCA) 1, SCA2, SCA3 and dentatorubral-pallidoluysian atrophy brains. Triple-labeling immunofluorescence demonstrated colocalization of ataxin-2 and ataxin-3 in NIIs containing expanded polyglutamine, irrespective of the disease examined. These in vivo findings indicate that polyglutamine proteins recruited into NIIs are not restricted to their expanded form. Among these proteins, recruitment of ataxin-2 was least frequent in every case examined, suggesting that the rate of recruitment partly depends on the protein transported into NIIs. Because other proteins lacking polyglutamine motif were not detected in NIIs, it is suggested that the presence of polyglutamine is a prerequisite for these proteins to be recruited into nucleus and to form NIIs. Interaction between expanded and non-expanded polyglutamine may play roles during these processes.
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PMID:Non-expanded polyglutamine proteins in intranuclear inclusions of hereditary ataxias--triple-labeling immunofluorescence study. 1156 29

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. CAG repeat expansions in the causative genes have been identified as the basic cause of several types of SCAs, and have been used for the diagnoses and classifications of patients with ataxia. In order to assess the frequency and CAG repeat size ranges of SCAs, and to establish an effective strategy for molecular diagnosis, we performed a molecular analysis of SCA1, SCA2, SCA3, SCA6, and SCA7 in 76 patients. These patients were as follows: 32 with dominant inheritance, 39 sporadic cases, and 5 with unknown family histories. The normal and affected CAG repeat size ranges were established at five SCA loci in Koreans, which was consistent with previous reports. The total prevalence of the five types of SCAs was 39.5% in the 76 patients with ataxia, regardless of their family history. It was 75.0% in the 32 families with a dominant inheritance. The most frequent type was SCA3 (15.8%), followed by SCA2 (14.5%). Both types combined formed 76.7% of the 30 patients with CAG expansions. SCA1, SCA6, and SCA7 were less frequent, affecting 3.9%, 2.6%, and 2.6% of the cases, respectively. This mutation spectrum is quite different from a previous report concerning Koreans, but is similar to the distributions that are seen in several ethnic populations worldwide. For a correct and effective diagnosis of SCAs, we suggest that a molecular diagnosis be undertaken, even in patients without a family history, as well as those with a family history. A stepwise approach is also recommended. Patients with ataxia should be tested for SCA2 and SCA3. Individuals testing negative should be tested for SCA1, SCA6, and SCA7.
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PMID:Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7. 1180 32

In patients with degenerative ataxia, various abnormalities in motor cortex activation by transcranial magnetic stimulation (TMS) have been observed, including a reduction of intracortical facilitation and a lengthening of the silent period. However, the groups of patients examined in previous studies were heterogeneous, involving patients with autosomal-dominant and idiopathic cerebellar ataxia, and showing different clinical features. The aim of our present study was to investigate whether differences in motor cortex activation by TMS could be observed in genetically defined subtypes of degenerative ataxia. We examined six patients with Friedreich's ataxia, three patients with spinocerebellar ataxia (SCA) type 1, seven patients with SCA2, 12 patients with SCA3, nine patients with SCA6 and 14 healthy controls. In all subjects, motor threshold, central motor conduction time, cortical silent period after TMS, and intracortical inhibition and facilitation (as assessed by TMS using a paired pulses paradigm) were determined. Additionally, F wave amplitudes evoked by electrical peripheral nerve stimulation were measured. We found a significant reduction of intracortical facilitation in SCA2 and SCA3 patients. Furthermore, motor threshold was elevated in SCA1, central motor conduction time was lengthened in patients with Friedreich's ataxia and SCA1, and F wave amplitudes were enlarged in all the genetic subgroups except for SCA6. Silent period and intracortical inhibition did not differ between patients and controls. We conclude that changes of intracortical facilitation induced by TMS and other excitability parameters of the motor system are not a common phenomenon in degenerative ataxia, but are restricted to specific subtypes. This points to differences in the underlying pathophysiological processes in genetic subtypes of ataxia.
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PMID:Motor cortex activation by transcranial magnetic stimulation in ataxia patients depends on the genetic defect. 1184 30

The nosology and aetiology of sporadic adult-onset ataxia are poorly understood. The aim of the present study was to answer the following questions: (i) How many sporadic ataxia patients have a genetic cause? (ii) How many sporadic ataxia patients suffer from multiple system atrophy (MSA)? (iii) Is there a specific association between sporadic ataxia and serum anti-glutamic acid decarboxylase (GAD) or antigliadin antibodies? and (iv) What are the clinical features of patients with unexplained sporadic ataxia? The study was performed in 112 patients who met the following inclusion criteria: (i) progressive ataxia; (ii) onset after 20 years; (iii) informative and negative family history (no similar disorders in first- and second-degree relatives; parents older than 50 years); and (iv) no established symptomatic cause. Thirty-two patients (29%) met the clinical criteria of possible (7%) or probable (22%) MSA. The Friedreich's ataxia mutation was found in five patients (4%), the spinocerebellar ataxia (SCA) 2 mutation in one (1%), the SCA3 mutation in two (2%) and the SCA6 mutation in seven (6%). The disease remained unexplained in 65 patients (58%). We did not detect anti-GAD antibodies in any of our patients. Antigliadin antibodies were present in 14 patients, 10 patients with unexplained ataxia (15%) and 4 patients with an established diagnosis (9%). Patients with unexplained sporadic ataxia had a median disease onset of 56.0 years. Decreased vibration sense (62%), decreased or absent ankle reflexes (40%), increased ankle reflexes (39%), dysphagia (38%) and extensor plantar responses and/or spasticity (34%) were the most frequent extracerebellar symptoms. Compared with MSA, disease progression was significantly slower.
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PMID:The aetiology of sporadic adult-onset ataxia. 1196 Aug 86

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.
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PMID:A patient homozygous for the SCA6 gene with retinitis pigmentosa. 1208 23

Expansions of trinucleotide repeats have been discovered in spinocerebellar ataxia (SCA) types 1, 2, 6, 7, 12, and 17, Machado-Joseph disease (MJD/SCA3), and dentatorubropallidoluysian atrophy (DRPLA). However, the frequency of familial SCA in Japan remains unclear. The number of trinucleotide repeats was determined for 1,286 patients. Three hundred and thirty families (523 cases) were autosomal dominant group (A), and 165 families were positive for family history but not autosomal dominant group (B), while the remaining 598 cases were the sporadic group (C). The frequency of SCA subtypes in autosomal dominant group was: 1) 5.5% for SCA1; 2) 2.4% for SCA2; 3) 27.6% for MJD/SCA3; 4) 25.5% for SCA6; 5) 0.3% for SCA17; and 6) 7.3% for DRPLA. Abnormal expansion of SCA12 was not detected. Another 31.5% of the patients in the autosomal dominant group had unknown genetic abnormalities. Within group B, SCA6 was the most prominent and within the sporadic group MJD/SCA3 and SCA6 were the most common subtypes observed. The disease-free survival curve of SCA6 was different from that of other SCAs and the mean age at onset for SCA6 was found to be later than that of the other types. Regional differences were observed in the relative rate of SCA subtypes. MJD/SCA3 appears more common in the Kanto and Kyushu districts of Japan, whereas SCA6 is most common in the Chugoku district. In order to establish an effective social welfare system for SCA patients, clinical course and regional differences in the prevalence of SCA subtypes must be taken into consideration.
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PMID:Difference in disease-free survival curve and regional distribution according to subtype of spinocerebellar ataxia: a study of 1,286 Japanese patients. 1211 98

The lateral reticular nucleus (LRT) of the medulla oblongata is a precerebellar nucleus involved in proprioception and somatomotor automatisms. We investigated this nucleus in five individuals with clinically diagnosed and genetically confirmed spinocerebellar ataxia type 3 (SCA3, Machado-Joseph disease). Polyethylene glycol-embedded 100 micro m thick sections stained for lipofuscin granules and Nissl material as well as Nissl-stained paraffin-embedded sections revealed severe destruction of the LRT in all SCA3 brains examined. Some of the few surviving neurones contained ataxin-3-immunopositive intranuclear inclusion bodies, as noted in other affected brain regions in SCA3. Along with the severe neuronal depletion, obvious astrogliosis was seen in the LRT of all SCA3 patients. The findings suggest that the LRT is a consistent target of the pathological process underlying SCA3. In view of its afferent and efferent connections, destruction of the LRT probably contributes to gait ataxia in individuals suffering from SCA3.
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PMID:Spinocerebellar ataxia type 3 (Machado-Joseph disease): severe destruction of the lateral reticular nucleus. 1218 56


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