Spinocerebellar Ataxia (spinocerebellar + ataxia)

Distribution by Scientific Domains

Kinds of Spinocerebellar Ataxia

  • dominant spinocerebellar ataxia

  • Terms modified by Spinocerebellar Ataxia

  • spinocerebellar ataxia type

  • Selected Abstracts


    A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3)

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2008
    C. Kieling
    Spinocerebellar ataxias (SCAs) are characterized by a heterogeneous set of clinical manifestations. Our aims were to assess the neurological features of SCA3, and to describe and test the feasibility, reliability, and validity of a comprehensive Neurological Examination Score for Spinocerebellar Ataxia (NESSCA). The NESSCA was administered to molecularly diagnosed SCA3 patients at an outpatient neurogenetics clinic. The scale, based on the standardized neurological examination, consisted of 18 items that yielded a total score ranging from 0 to 40. The score's interrater reliability and internal consistency were investigated, and a principal components analysis and a correlation with external measures were performed. Ninety-nine individuals were evaluated. Interrater reliability ranged from 0.8 to 1 across individual items (P < 0.001); internal consistency, indicated by Cronbach's alpha, was 0.77. NESSCA scores were significantly correlated with measures of disease severity: disease stage (rho = 0.76, P < 0.001), duration (rho = 0.56, P < 0.001), and length of CAG repeat (rho = 0.30, P < 0.05). NESSCA was a reliable measure for the assessment of distinct neurological deficits in SCA3 patients. Global scores correlated with all external variables tested, showing NESSCA to be a comprehensive measure of disease severity that is both clinically useful and scientifically valid. [source]


    Spinocerebellar ataxia 14: Novel mutation in exon 2 of PRKCG in a German family

    MOVEMENT DISORDERS, Issue 2 2007
    Dagmar Nolte PhD
    Abstract We describe a novel mutation in the gene coding for protein kinase C gamma (PRKCG) in patients of a German family affected with slowly progressive gait ataxia, dysarthria, and nystagmus. The G/T missense mutation occurred in exon 2 of PRKCG and results in a substitution of glycine by valine (G63V) in the evolutionarily highly conserved cysteine-rich region 1/C1 domain of PRKCG. Among the 20 mutations described to date, this is the first mutation located in exon 2 of PRKCG. © 2006 Movement Disorder Society [source]


    A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3)

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2008
    C. Kieling
    Spinocerebellar ataxias (SCAs) are characterized by a heterogeneous set of clinical manifestations. Our aims were to assess the neurological features of SCA3, and to describe and test the feasibility, reliability, and validity of a comprehensive Neurological Examination Score for Spinocerebellar Ataxia (NESSCA). The NESSCA was administered to molecularly diagnosed SCA3 patients at an outpatient neurogenetics clinic. The scale, based on the standardized neurological examination, consisted of 18 items that yielded a total score ranging from 0 to 40. The score's interrater reliability and internal consistency were investigated, and a principal components analysis and a correlation with external measures were performed. Ninety-nine individuals were evaluated. Interrater reliability ranged from 0.8 to 1 across individual items (P < 0.001); internal consistency, indicated by Cronbach's alpha, was 0.77. NESSCA scores were significantly correlated with measures of disease severity: disease stage (rho = 0.76, P < 0.001), duration (rho = 0.56, P < 0.001), and length of CAG repeat (rho = 0.30, P < 0.05). NESSCA was a reliable measure for the assessment of distinct neurological deficits in SCA3 patients. Global scores correlated with all external variables tested, showing NESSCA to be a comprehensive measure of disease severity that is both clinically useful and scientifically valid. [source]


    Ataxic mutant mice with defects in Ca2+ channel ,1A subunit gene: morphological and functional abnormalities in cerebellar cortical neurons

    CONGENITAL ANOMALIES, Issue 2 2000
    Kazuhiko Sawada
    ABSTRACT This review summarizes recent studies in the morphological and functional abnormalities of cerebella in three ataxic mutant mice, i.e. tottering mouse, leaner mouse, and rolling mouse Nagoya (RMN). These mutants carry mutations in the Ca2+ channel ,1A subunit gene, and become useful models for human neurological diseases such as episodic ataxia type-2, familial hemiplegic migraine, and spinocerebellar ataxia type-6. All three mutants exhibited altered morphology of the Purkinje cells, ectopic synaptic contacts between granule cell axons (parallel fibers) and Purkinje cell dendritic spines and abnormal expression of tyrosine hydroxylase in Purkinje cells. In leaner mice, Purkinje cell loss was observed in alternating sagittal compartments of the cerebellar cortex corresponding to the Zebrin II-negative zones. The mutated Ca2+ channel ,1A subunit was highly expressed in granule and Purkinje cells, and the P-type Ca2+ currents in Purkinje cells were selectively reduced in the mutant mice. Therefore, we concluded that altered Ca2+ currents through the mutated Ca2+ channel ,1A subunit might be involved in the functional and morphological abnormalities in granule and Purkinje cells, and might result in expressions of behavioral phenotypes including ataxia. Increased levels of corticotropin-releasing factor and cholecystokinin in some climbing and mossy fibers were observed in RMN. These neuropeptides modulated the excitability of granule and Purkinje cells, indicating the possible expression of ataxic symptoms. [source]


    Hereditary spastic paraplegia or spinocerebellar ataxia?

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2009
    Not always as easy as it seems
    No abstract is available for this article. [source]


    A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3)

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2008
    C. Kieling
    Spinocerebellar ataxias (SCAs) are characterized by a heterogeneous set of clinical manifestations. Our aims were to assess the neurological features of SCA3, and to describe and test the feasibility, reliability, and validity of a comprehensive Neurological Examination Score for Spinocerebellar Ataxia (NESSCA). The NESSCA was administered to molecularly diagnosed SCA3 patients at an outpatient neurogenetics clinic. The scale, based on the standardized neurological examination, consisted of 18 items that yielded a total score ranging from 0 to 40. The score's interrater reliability and internal consistency were investigated, and a principal components analysis and a correlation with external measures were performed. Ninety-nine individuals were evaluated. Interrater reliability ranged from 0.8 to 1 across individual items (P < 0.001); internal consistency, indicated by Cronbach's alpha, was 0.77. NESSCA scores were significantly correlated with measures of disease severity: disease stage (rho = 0.76, P < 0.001), duration (rho = 0.56, P < 0.001), and length of CAG repeat (rho = 0.30, P < 0.05). NESSCA was a reliable measure for the assessment of distinct neurological deficits in SCA3 patients. Global scores correlated with all external variables tested, showing NESSCA to be a comprehensive measure of disease severity that is both clinically useful and scientifically valid. [source]


    Self-rated health status in spinocerebellar ataxia,Results from a European multicenter study,

    MOVEMENT DISORDERS, Issue 5 2010
    Tanja Schmitz-Hübsch MD
    Abstract Patient-based measures of subjective health status are increasingly used as outcome measures in interventional trials. We aimed to determine the variability and predictors of subjective health ratings in a possible target group for future interventions: the spinocerebellar ataxias (SCAs). A consecutive sample of 526 patients with otherwise unexplained progressive ataxia and genetic diagnoses of SCA1 (117), SCA2 (163), SCA3 (139), and SCA6 (107) were enrolled at 18 European referral centers. Subjective health status was assessed with a generic measure of health related quality of life, the EQ-5D (Euroqol) questionnaire. In addition, we performed a neurological examination and a screening questionnaire for affective disorders (patient health questionnaire). Patient-reported health status was compromised in patients of all genotypes (EQ-5D visual analogue scale (EQ-VAS) mean 61.45 ± 20.8). Specifically, problems were reported in the dimensions of mobility (86.9% of patients), usual activities (68%), pain/discomfort (49.4%), depression/anxiety (46.4%), and self care (38.2%). Multivariate analysis revealed three independent predictors of subjective health status: ataxia severity, extent of noncerebellar involvement, and the presence of depressive syndrome. This model explained 30.5% of EQ-VAS variance in the whole sample and might be extrapolated to other SCA genotypes. © 2010 Movement Disorder Society [source]


    Genetic analysis of SCA 2 and 3 repeat expansions in essential tremor and atypical Parkinsonism

    MOVEMENT DISORDERS, Issue 13 2007
    Eng-King Tan MD
    Abstract Anecdotal reports suggest that patients with spinocerebellar ataxia (SCA 2) patients can present with postural tremor with ataxia. We determined the prevalence of SCA2 and SCA3 mutations in a cohort of ET and atypical Parkinsonism patients. A total of 277 subjects comprising of 177 ET and 100 atypical Parkinsonism were examined. We identified one positive case of SCA3 among those who were diagnosed with ET, yielding a prevalence of 0.5%, but a zero prevalence among our atypical Parkinsonism patients. No study subjects carried an abnormal SCA2 repeat expansion. Our study highlights that SCA3 can present initially with ET symptoms, expanding the spectrum of genetic diseases that can be associated with ET-like phenotype. Routine screening for SCA2 and SCA3 in ET and atypical Parkinsonism patients may not be cost effective. However, in the long-term follow-up of patients who present with an ET phenotype, clinicians should be vigilant for other neurological signs, which may be point to an alternate diagnosis. © 2007 Movement Disorder Society [source]


    Novel PRKCG/SCA14 mutation in a Dutch spinocerebellar ataxia family: Expanding the phenotype

    MOVEMENT DISORDERS, Issue 7 2006
    Monique H.M. Vlak MD
    Abstract We report on a family with an autosomal dominant cerebellar ataxia in which we identified a novel mutation in exon 5 of the PRKCG/SCA14 gene that results in a Val138Glu substitution in the encoded protein PKC,. While most affected subjects displayed a late-onset uncomplicated form of spinocerebellar ataxia with occasional mild extrapyramidal features (such as postural tremor), one patient presented with a very mild nonprogressive ataxia since the age of 3 years and predominant multifocal myoclonus. © 2006 Movement Disorder Society [source]


    Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients

    MOVEMENT DISORDERS, Issue 2 2006
    a T. Draga
    Abstract The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1,3, 6,8, 12, 17; dentate,rubro,pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia. © 2005 Movement Disorder Society [source]


    Clinical feature profile of spinocerebellar ataxia type 1,8 predicts genetically defined subtypes

    MOVEMENT DISORDERS, Issue 11 2005
    Matthias Maschke MD
    Abstract An increasing number of genetically defined types of spinocerebellar ataxia (SCA) have been reported in the past decade. Phenotype,genotype correlation studies have suggested a broad overlap between SCA types. The aim of the present study was to identify patterns of clinical features that were likely to distinguish between SCA types and to test the specificity and sensitivity of these signs and symptoms using a Bayesian classifier. In total, 127 patients from 50 families with SCA types 1 to 8 were examined using a worksheet with a panel of 33 symptoms and signs. By computing the probabilities of each trait for each SCA type, we rated the predictive value of each feature for each form of ataxia and then combined the probabilities for the entire panel of traits to construct a Bayesian classifier. Results of this analysis were summarized in a simpler, more operator-based algorithm. Patients with SCA5, SCA6, and SCA8 demonstrated a predominant cerebellar syndrome, whereas patients with SCA1, SCA2, SCA3, SCA4, and SCA7 frequently had clinical features indicating an extracerebellar involvement. The Bayesian classifier predicted the SCA type in 78% of patients with sensitivities between 60 and 100% and specificities between 94 and 98.2%. The highest sensitivity to correctly predict the true SCA type was found for SCA5, SCA7, and SCA8. Sensitivities and specificities found in the present study validate the use of algorithms to help to prioritize specific SCA gene testing, which will help to reduce costs for gene testing. © 2005 Movement Disorder Society [source]


    SCA2 may present as levodopa-responsive parkinsonism

    MOVEMENT DISORDERS, Issue 4 2003
    Haydeh Payami PhD
    Abstract Some kindreds with familial parkinsonism exhibit genetic anticipation, suggesting possible involvement of trinucleotide repeat expansion. Recent reports have shown trinucleotide repeat expansions in the spinocerebellar ataxia 2 (SCA2) gene in patients with levodopa-responsive parkinsonism. We tested 136 unrelated patients with familial parkinsonism for SCA2 mutations. Two probands had borderline mutations; the rest were normal. (,31 repeats is normal, 32,35 is borderline, ,36 is pathogenic). The expanded allele segregated with neurological signs in one kindred. The absence of borderline mutations in the normal population, and the co-segregation of the expanded allele with neurological signs in one kindred suggest that SCA2 mutations may be responsible for a subset of familial parkinsonism. © 2002 Movement Disorder Society [source]


    Isolated vitamin E deficiency with demyelinating neuropathy

    MUSCLE AND NERVE, Issue 2 2005
    Vinod Puri MD
    Abstract A 22-year-old man, with a past history of generalized tonic-clonic seizures treated with phenobarbital, presented with spinocerebellar ataxia. The electrophysiological studies revealed a demyelinating motor-sensory neuropathy. The serum vitamin E level was low. Sural nerve biopsy revealed loss of large myelinated fibers with evidence of remyelination. Vitamin E supplementation led to clinical and electrophysiological recovery of sensory conduction and evoked potentials. Motor nerve conduction, however, showed only partial recovery. Vitamin E deficiency leading to a demyelinating neuropathy, as in the present case, suggests that the full spectrum of the disease entity is not fully defined. Muscle Nerve, 2005 [source]


    Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2

    ANNALS OF NEUROLOGY, Issue 3 2004
    Luis Velázquez-Pérez MD
    We assessed maximal saccade velocity (MSV) in 82 spinocerebellar ataxia type 2 (SCA2) patients and 80 controls, correlating it to disease duration, polyglutamine expansion size, age at onset, ataxia score, age, and sex. Little overlap with normal values was found even at earliest stages. Stepwise linear regression analysis showed that 60-degree MSV was strongly influenced by polyglutamine size and less by disease duration, whereas the reverse was found for ataxia score. Saccade velocity thus is a sensitive, quite specific, and objective endophenotype, useful to search polyglutamine modifier genes. Ann Neurol 2004;56:444,447 [source]


    Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17)

    ANNALS OF NEUROLOGY, Issue 3 2003
    Arndt Rolfs MD
    Autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders clinically characterized by late-onset ataxia and variable other manifestations. Genetically and clinically, SCA is highly heterogeneous. Recently, CAG repeat expansions in the gene encoding TATA-binding protein (TBP) have been found in a new form of SCA, which has been designated SCA17. To estimate the frequency of SCA17 among white SCA patients and to define the phenotypic variability, we determined the frequency of SCA17 in a large sample of 1,318 SCA patients. In total, 15 patients in four autosomal dominant SCA families had CAG/CAA repeat expansions in the TBP gene ranging from 45 to 54 repeats. The clinical features of our SCA17 patients differ from other SCA types by manifesting with psychiatric abnormalities and dementia. The neuropathology of SCA17 can be classified as a "pure cerebellar" or "cerebello-olivary" form of ataxia. However, intranuclear neuronal inclusion bodies with immunoreactivity to anti-TBP and antipolyglutamine were much more widely distributed throughout the brain gray matter than in other SCAs. Based on clinical and genetic data, we conclude that SCA17 is rare among white SCA patients. SCA17 should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia. [source]


    Spectrin mutations in spinocerebellar ataxia (SCA)

    BIOESSAYS, Issue 8 2006
    Peter Bauer
    Recently, ,III spectrins have been recognized as ataxia disease genes, with the identification by Ikeda and co-workers of pathogenic mutations in the SPTBN2 gene in three large (and mapped) SCA5 families of American and European origin.(1) With their discovery, the large "Lincoln" family has been traced back to the underlying genetic defect for the slowly progressive cerebellar ataxia. In addition, the involvement of this component of the cytoskeleton directs attention towards the possible role of organelle stability during neurodegeneration. The findings suggest that the mechanical properties of neurons and their dynamics may be as important as altered Ca2+ homeostasis, transcriptional dysregulation, and impaired protein degradation in neurodegeneration conditions. BioEssays 28: 785,787, 2006. © 2006 Wiley Periodicals, Inc. [source]


    Heart rate variability in type 2 spinocerebellar ataxia

    ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2010
    J. Montes-Brown
    Montes-Brown J, Sánchez-Cruz G, García AM, Báez ME, Velázquez-Pérez L. Heart rate variability in type 2 spinocerebellar ataxia. Acta Neurol Scand: 2010: 122: 329,335. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives,,, To explore cardiovascular autonomic regulation in Spinocerebellar ataxia type 2 (SCA2) patients, using heart rate variability (HRV) analysis and neurophysiologic autonomic reflex tests, and determine relations and causal related factors of dysautonomia in SCA2. Materials and methods,,, Heart rate variability indices for 5 min series of RR intervals were analyzed in 97 SCA2 patients, assessed quantitatively for somatic and autonomic nervous system complaints applying the International Cooperative Ataxia Rating Scale and Scales for Outcomes in Parkinson's disease (SCOPA-AUT), respectively. Autonomic testing included: resting control, standing, Valsalva maneuver and deep breathing. Results,,, Mean RR, long- and short-term variability indices and spectral density power (LF, HF) indices were lower in the patients group, whereas LF/HF ratio and LF (nu) were higher. Highly differences between groups were observed for seven diagnostic autonomic test indices. Significant correlations were found between different clinical and demographic indices and between clinical indices and some HRV indices. Conclusions,,, We confirm the presence of cardiovascular autonomic dysfunction in a large group of SCA2 patients. [source]


    Self-rated health status in spinocerebellar ataxia,Results from a European multicenter study,

    MOVEMENT DISORDERS, Issue 5 2010
    Tanja Schmitz-Hübsch MD
    Abstract Patient-based measures of subjective health status are increasingly used as outcome measures in interventional trials. We aimed to determine the variability and predictors of subjective health ratings in a possible target group for future interventions: the spinocerebellar ataxias (SCAs). A consecutive sample of 526 patients with otherwise unexplained progressive ataxia and genetic diagnoses of SCA1 (117), SCA2 (163), SCA3 (139), and SCA6 (107) were enrolled at 18 European referral centers. Subjective health status was assessed with a generic measure of health related quality of life, the EQ-5D (Euroqol) questionnaire. In addition, we performed a neurological examination and a screening questionnaire for affective disorders (patient health questionnaire). Patient-reported health status was compromised in patients of all genotypes (EQ-5D visual analogue scale (EQ-VAS) mean 61.45 ± 20.8). Specifically, problems were reported in the dimensions of mobility (86.9% of patients), usual activities (68%), pain/discomfort (49.4%), depression/anxiety (46.4%), and self care (38.2%). Multivariate analysis revealed three independent predictors of subjective health status: ataxia severity, extent of noncerebellar involvement, and the presence of depressive syndrome. This model explained 30.5% of EQ-VAS variance in the whole sample and might be extrapolated to other SCA genotypes. © 2010 Movement Disorder Society [source]


    Huntington's disease phenocopies are clinically and genetically heterogeneous

    MOVEMENT DISORDERS, Issue 5 2008
    Edward J. Wild MRCP
    Abstract Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD-like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD-like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral-pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty-five patients with syndromes consistent with HD, who were HD expansion-negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. © 2008 Movement Disorder Society [source]


    Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients

    MOVEMENT DISORDERS, Issue 2 2006
    a T. Draga
    Abstract The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1,3, 6,8, 12, 17; dentate,rubro,pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia. © 2005 Movement Disorder Society [source]


    Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17)

    ANNALS OF NEUROLOGY, Issue 3 2003
    Arndt Rolfs MD
    Autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders clinically characterized by late-onset ataxia and variable other manifestations. Genetically and clinically, SCA is highly heterogeneous. Recently, CAG repeat expansions in the gene encoding TATA-binding protein (TBP) have been found in a new form of SCA, which has been designated SCA17. To estimate the frequency of SCA17 among white SCA patients and to define the phenotypic variability, we determined the frequency of SCA17 in a large sample of 1,318 SCA patients. In total, 15 patients in four autosomal dominant SCA families had CAG/CAA repeat expansions in the TBP gene ranging from 45 to 54 repeats. The clinical features of our SCA17 patients differ from other SCA types by manifesting with psychiatric abnormalities and dementia. The neuropathology of SCA17 can be classified as a "pure cerebellar" or "cerebello-olivary" form of ataxia. However, intranuclear neuronal inclusion bodies with immunoreactivity to anti-TBP and antipolyglutamine were much more widely distributed throughout the brain gray matter than in other SCAs. Based on clinical and genetic data, we conclude that SCA17 is rare among white SCA patients. SCA17 should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia. [source]


    FUS-Immunoreactive Intranuclear Inclusions in Neurodegenerative Disease

    BRAIN PATHOLOGY, Issue 3 2010
    John Woulfe
    Abstract Neuronal intranuclear inclusions (NIIs) are a histopathological hallmark of several neurodegenerative disorders. However, the role played by NIIs in neurodegenerative pathogenesis remains enigmatic. Defining their molecular composition represents an important step in understanding the pathophysiology of these disorders. Recently, a nuclear protein, "fused-in-sarcoma" (FUS) was identified as the pathological protein in two forms of frontotemporal lobar degeneration (FTLD-IF, formerly known as neuronal intermediate filament inclusion disease, and FTLD-UPS, formerly known as atypical FTLD-U), both of which are characterized by the presence of NII. The objective of the present study was to determine the range of neurodegenerative disorders characterized by FUS-positive NIIs. Immunostaining for FUS revealed intense reactivity of NIIs in FTLD-IF and FTLD-UPS as well as in Huntington's disease, spinocerebellar ataxias 1 and 3, and neuronal intranuclear inclusion body disease. In contrast, there was no FUS staining of NIIs in inherited forms of FTLD-TDP caused by GRN and VCP mutations, fragile-X-associated tremor ataxia syndrome, or oculopharyngeal muscular dystrophy. In a cell culture model of Huntington's disease, NIIs were intensely FUS-positive. NII-bearing cells displayed loss of the normal diffuse nuclear pattern of FUS staining. This suggests that sequestration of nuclear FUS by NIIs may interfere with its normal nuclear localization. [source]


    Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3

    ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2010
    S. J. Sriranjini
    Sriranjini SJ, Pal PK, Krishna N, Sathyaprabha TN. Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3. Acta Neurol Scand: 2010: 122: 323,328. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, Evaluation of pulmonary function in patients with spinocerebellar ataxias (SCA) 1, 2 and 3 without clinical evidence of pulmonary dysfunction. Methods,,, Thirty patients (F:M = 7:23; age: 35 ± 11.3 years; SCA1 , 13, SCA2 , 9 and SCA3 , 8) without clinical manifestations of respiratory dysfunction and 30 controls underwent pulmonary function tests. The percentage predicted values of forced vital capacity (FVC), volume of air exhaled during first second of FVC (FEV1), peak expiratory flow rate (PEFR) and maximal voluntary ventilation (MVV), actual values of maximal inspiratory and expiratory pressures (MIP and MEP in mmHg), and ratios of actual values of FEV1/FVC (%) and FEV1/PEFR (ml/l/min) were analyzed. Results,,, Compared with controls SCA patients had significant reductions of FVC (71.1 ± 17.5 vs 85.5 ± 18.7; P < 0.01), PEFR (51.5 ± 20.7 vs 77.1 ± 24.9; P < 0.001), MVV (64.4 ± 21.6 vs 97.2 ± 22.7; P < 0.001), MIP (27.7 ± 16.8 vs 50.1 ± 15.1; P < 0.001) and MEP (38.1 ± 18.7 vs 74.7 ± 16.0; P < 0.001), elevation of FEV1/PEFR (10.5 ± 2.8 vs 7.4 ± 2.1; P < 0.001), but no significant change of FEV1 and FEV1/FVC. FEV1/PEFR correlated positively with illness duration and MVV negatively with severity of illness. Conclusions,,, The present study showed subclinical restrictive type of pulmonary dysfunction in SCA, and possible presence of upper airway obstruction. Chest physiotherapy and breathing exercises should be introduced early in management of SCA. [source]


    A comparative study of cardiac dysautonomia in autosomal dominant spinocerebellar ataxias and idiopathic sporadic ataxias

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009
    M. Netravathi
    Objectives,,, Comparative evaluation of cardiac dysautonomia in spinocerebellar ataxias (SCA) and idiopathic sporadic ataxias (IA) not fulfilling the criteria of multiple system atrophy. Material and methods,,, Cardiac autonomic functions were evaluated in 14 SCA (SCA1 = 6, SCA2 = 5 and SCA3 = 3) and 10 IA patients, comparable for age, age at onset, duration and severity of illness. The results were categorized as early, definitive, or severe autonomic involvement (EI, DI and SI respectively) based on the degree of abnormalities on tests of parasympathetic and sympathetic pathways. Results,,, Cardiac autonomic dysfunction was present in all (EI = 25.0%, DI = 41.7% and SI = 33.3%), parasympathetic dysfunction being an early feature. SI was most often present in SCA3 (100%), followed by those with SCA1 (66.7%), and SCA2 (20%) and none in IA. Conclusions,,, Cardiac dysautonomia was common in both SCA and IA, although the severity was greater in SCA. Among SCAs, the severity was greatest in SCA3, followed by SCA2 and least in SCA1. [source]


    The occurrence of dominant spinocerebellar ataxias among 251 Finnish ataxia patients and the role of predisposing large normal alleles in a genetically isolated population

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2005
    V. Juvonen
    Objectives,,, Frequency and distribution of dominant ataxias caused by dynamic mutations may vary in different populations, which has been explained on the basis of relative frequency of predisposing normal alleles. The aim of the study was to evaluate the occurrence of spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA) in Finland, and to investigate the role of predisposing normal alleles in a genetically homogenous population. Material and methods,,, Mutation analyses for SCA1, 2, 3, 6, 7, 8, 10, 12, 17, and DRPLA and frataxin genes were performed for 251 unrelated Finnish patients who presented with progressive ataxia disorder. Results,,, Expansions of SCA1, SCA2, SCA6, SCA7, SCA8, and SCA17 genes were detected in 2, 1, 1, 7, 22, and 1 patients, respectively. Altogether, 39 and 7% of dominant and sporadic SCA patients, respectively, harboured expansions at some of the investigated loci. Normal variation, collected from 477 to 502 chromosomes at each disease loci, revealed that Finns were different from the Japanese but largely similar to other Caucasians. Conclusions,,, Lack of SCA3 and excess of SCA8 are characteristic to the Finnish population. Homozygosity for the SCA8 expansion increases penetrance. Frequencies of large normal alleles at the SCA loci predict poorly prevalence of the respective diseases in Finland. Prioritization in DNA testing, based on ethnic origin and geographical location, is recommendable in Finland, and analogous approach may be applied to other countries as well. [source]