57 results on '"Spinocerebellar Degenerations"'
Search Results
2. Arterial spin labeling MR imaging for the clinical detection of cerebellar hypoperfusion in patients with spinocerebellar degeneration
- Author
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Akiko Matsunaga, Tadanori Hamano, Yuki Kitazaki, Yasunari Nakamoto, Osamu Yamamura, Tetsuya Tsujikawa, Kouji Hayashi, Makoto Yoneda, Masamichi Ikawa, Hidehiko Okazawa, Katsuya Sugimoto, and Hirohiko Kimura
- Subjects
Male ,Cerebellum ,Degeneration (medical) ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,otorhinolaryngologic diseases ,medicine ,Humans ,Aged ,Spinocerebellar Degenerations ,Aged, 80 and over ,Tomography, Emission-Computed, Single-Photon ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Blood flow ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,nervous system ,Neurology ,Cerebral blood flow ,Cerebrovascular Circulation ,Female ,Spin Labels ,Neurology (clinical) ,Nuclear medicine ,business ,Perfusion ,030217 neurology & neurosurgery ,Emission computed tomography - Abstract
Purpose The aim of this study was to evaluate the clinical utility of arterial spin labeling (ASL) magnetic resonance imaging (MRI) for the detection of cerebellar hypoperfusion in patients with spinocerebellar degeneration (SCD). Methods Regional cerebral blood flow (CBF) were obtained from ASL and 123I-IMP single-photon emission computed tomography (SPECT) images by volume-of-interest analysis in patients with SCD (n = 16). Regional CBF were also measured by ASL in age-matched controls (n = 19) and by SPECT in separate controls (n = 17). The cerebellar CBF values were normalized to the CBF values for the whole gray matter (nCBF) in ASL and SPECT. Results The mean cerebellar nCBF measured by ASL was lower in patients with SCD (0.70 ± 0.09) than in the controls (0.91 ± 0.05) (p Conclusions ASL imaging showed decreased cerebellar blood flow, which correlated with that measured by SPECT, in patients with SCD. These findings suggest the clinical utility of noninvasive MRI with ASL for detecting cerebellar hypoperfusion in addition to atrophy, which would aid the diagnosis of SCD.
- Published
- 2018
3. Rating scales and biomarkers for CAG-repeat spinocerebellar ataxias: Implications for therapy development
- Author
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Puneet Opal, Chih-Chun Lin, Meng Ling Chen, Liana S. Rosenthal, and Sheng-Han Kuo
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,business.industry ,Clinical study design ,Disease progression ,Bioinformatics ,medicine.disease ,Article ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Neurology ,Neuroimaging ,Rating scale ,Track disease ,Spinocerebellar ataxia ,medicine ,Biomarker (medicine) ,Humans ,Spinocerebellar Ataxias ,030212 general & internal medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Biomarkers ,Spinocerebellar Degenerations - Abstract
Spinocerebellar ataxias (SCAs) are a group of dominantly-inherited cerebellar ataxias, among which CAG expansion-related SCAs are most common. These diseases have very high penetrance with defined disease progression, and emerging therapies are being developed to provide either symptomatic or disease-modifying benefits. In clinical trial design, it is crucial to incorporate biomarkers to test target engagement or track disease progression in response to therapies, especially in rare diseases such as SCAs. In this article, we review the available rating scales and recent advances of biomarkers in CAG-repeat SCAs. We divided biomarkers into neuroimaging, body fluid, and physiological studies. Understanding the utility of each biomarker will facilitate the design of robust clinical trials to advance therapies for SCAs.
- Published
- 2020
4. Sequence configuration of spinocerebellar ataxia type 8 repeat expansions in a Japanese cohort of 797 ataxia subjects
- Author
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Mamut Rayle, Takanori Yokota, Hidehiro Mizusawa, Miwa Higashi, Yajun Hu, Kazumasa Soga, Michi Okita, Kinya Ishikawa, Takashi Ishii, Yuji Hashimoto, Kokoro Ozaki, and Nozomu Sato
- Subjects
Adult ,0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Ataxia ,Adolescent ,Biology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Japan ,Prevalence ,medicine ,Humans ,Age of Onset ,Allele ,Spinocerebellar Degenerations ,Sequence (medicine) ,Genetics ,Middle Aged ,medicine.disease ,Penetrance ,030104 developmental biology ,Neurology ,Spinocerebellar ataxia ,RNA, Long Noncoding ,Neurology (clinical) ,Age of onset ,medicine.symptom ,Trinucleotide Repeat Expansion ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery - Abstract
Spinocerebellar ataxia type 8 (SCA8), an autosomal dominant neurodegenerative disorder showing slowly progressive cerebellar ataxia, is caused by a tri-nucleotide CTG repeat expansion (CTGexp) in the SCA8 gene. As the CTGexp is not fully penetrant, the significance of screening CTGexp in ataxia subjects remains obscure. We tested SCA8 CTGexp in a cohort of 797 ataxia subjects, and if present, its sequence configuration was analyzed. CTGexp was found in 16 alleles from 14 individuals, 2 of which was homozygous for CTGexp. Nucleotide sequencing disclosed 3 types of CTGexp sequence configurations: uninterrupted CTGexp, tri-nucleotide CTA interruption and CCG interruption. The 2 individuals with homozygous expansions were both sporadic cases with clinical features compatible with SCA8, supporting gene dosage effect. Seven out of 14 CTGexp-positive subjects were also carriers of other SCA expansions [Machado-Joseph disease (n=1), SCA6 (n=3) and SCA31 (n=3)], whereas 7 others were not complicated with such major SCAs. Ages of onset in subjects with pure CTGexp tended to be earlier than those with interrupted CTGexp among the 7 subjects not complicated by major SCAs, suggesting that pure CTGexp have stronger pathogenic effect than interrupted CTGexps. The present study underscores importance of disclosing sequence configuration when testing SCA8.
- Published
- 2017
5. A Chinese Han pedigree with Huntington disease mimicking spinocerebellar ataxia.
- Author
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Mao C, Su Y, Wang H, Fan L, Zheng H, Wang T, Li X, Zhang S, Hu Z, Luo H, Yang J, Shi C, and Xu Y
- Subjects
- China, Humans, Pedigree, Huntington Disease diagnosis, Huntington Disease genetics, Spinocerebellar Ataxias diagnosis, Spinocerebellar Ataxias genetics, Spinocerebellar Degenerations
- Published
- 2021
- Full Text
- View/download PDF
6. Differential effects of thyrotropin releasing hormone (TRH) on motor execution and motor adaptation process in patients with spinocerebellar degeneration
- Author
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Takahiro Shimizu, Makiko Nagai, R. Tsutsumi, Kazutoshi Nishiyama, Naomi Tominaga, Ritsuko Hanajima, Kazutaka Shimizu, and Yoshikazu Ugawa
- Subjects
endocrine system ,Cerebellum ,medicine.medical_specialty ,Ataxia ,Cerebellar Ataxia ,genetic structures ,Thyrotropin-releasing hormone ,Degeneration (medical) ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Japan ,medicine ,Humans ,Spinocerebellar Ataxias ,030212 general & internal medicine ,Thyrotropin-Releasing Hormone ,Spinocerebellar Degenerations ,Cerebellar ataxia ,business.industry ,Differential effects ,medicine.anatomical_structure ,Neurology ,Neurology (clinical) ,medicine.symptom ,business ,Prism adaptation ,030217 neurology & neurosurgery ,Motor execution - Abstract
Background The cerebellum is known to play a crucial role in sensori-motor adaptation, which includes the prism adaptation. TRH has been widely used as a treatment for cerebellar ataxia in Japan, however effects of TRH on cerebellar adaptation process have not been studied. Here, we studied effects of TRH treatment on the prism adaptation task. Methods Eighteen spinocerebellar degeneration (SCD) patients participated in this study. The participants received intravenous injection of 2 mg/day protirelin tartrate once a day for 14 days. In the prism adaptation task, the participants reached to the target on the screen wearing wedge prisms. We compared the Scale for Assessment and Rating of Ataxia (SARA), baseline errors and the aftereffect (AE) of the prism adaptation task between before and after TRH therapy. Results TRH therapy improved SARA significantly (p = .005). Multiple regression analysis revealed that improvement of SARA score was mainly due to improvement of “Stance” category score. TRH decreased baseline errors of the prism adaptation task (p = .021), while unaffected AEs (p = .252). Conclusion TRH differentially affected clinical cerebellar ataxia including baseline reaching performance in the prism adaptation task, whereas TRH did not affect the learning process of prism adaptation. Different cerebellar functional aspects may underlie the learning process of sensori-motor adaptation and simple motor execution (clinically evaluated cerebellar ataxia).
- Published
- 2020
7. Rating scales and biomarkers for CAG-repeat spinocerebellar ataxias: Implications for therapy development.
- Author
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Chen ML, Lin CC, Rosenthal LS, Opal P, and Kuo SH
- Subjects
- Biomarkers, Humans, Spinocerebellar Ataxias genetics, Spinocerebellar Ataxias therapy, Spinocerebellar Degenerations
- Abstract
Spinocerebellar ataxias (SCAs) are a group of dominantly-inherited cerebellar ataxias, among which CAG expansion-related SCAs are most common. These diseases have very high penetrance with defined disease progression, and emerging therapies are being developed to provide either symptomatic or disease-modifying benefits. In clinical trial design, it is crucial to incorporate biomarkers to test target engagement or track disease progression in response to therapies, especially in rare diseases such as SCAs. In this article, we review the available rating scales and recent advances of biomarkers in CAG-repeat SCAs. We divided biomarkers into neuroimaging, body fluid, and physiological studies. Understanding the utility of each biomarker will facilitate the design of robust clinical trials to advance therapies for SCAs., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
8. Targeting the enhanced ER stress response in Marinesco-Sjögren syndrome
- Author
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Tomohiro Morio, Masatoshi Takagi, Yukiko K. Hayashi, Motoharu Kawai, Muneaki Matsuo, Takeo Isagai, Setsuko Hasegawa, Ayako Kashimada, Tsuyoshi Uchiyama, and Masahide Goto
- Subjects
0301 basic medicine ,Male ,X-Box Binding Protein 1 ,XBP1 ,Cell Survival ,MAP Kinase Kinase 4 ,Marinesco–Sjögren syndrome ,Apoptosis ,MAP Kinase Kinase Kinase 5 ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,Downregulation and upregulation ,medicine ,Guanine Nucleotide Exchange Factors ,Humans ,Lymphocytes ,Child ,Cell Line, Transformed ,Spinocerebellar Degenerations ,Membrane Potential, Mitochondrial ,Endoplasmic reticulum ,Tauroursodeoxycholic acid ,Tunicamycin ,Middle Aged ,medicine.disease ,Endoplasmic Reticulum Stress ,Flow Cytometry ,digestive system diseases ,030104 developmental biology ,Neurology ,chemistry ,Unfolded protein response ,Cancer research ,Female ,Neurology (clinical) - Abstract
Background and objective Marinesco-Sjogren syndrome (MSS) is an autosomal recessive infantile-onset disorder characterized by cataracts, cerebellar ataxia, and progressive myopathy caused by mutation of SIL1. In mice, a defect in SIL1 causes endoplasmic reticulum (ER) chaperone dysfunction, leading to unfolded protein accumulation and increased ER stress. However, ER stress and the unfolded protein response (UPR) have not been investigated in MSS patient-derived cells. Methods Lymphoblastoid cell lines (LCLs) were established from four MSS patients. Spontaneous and tunicamycin-induced ER stress and the UPR were investigated in MSS-LCLs. Expression of UPR markers was analyzed by western blotting. ER stress-induced apoptosis was analyzed by flow cytometry. The cytoprotective effects of ER stress modulators were also examined. Results MSS-LCLs exhibited increased spontaneous ER stress and were highly susceptible to ER stress-induced apoptosis. The inositol-requiring protein 1α (IRE1α)-X-box-binding protein 1 (XBP1) pathway was mainly upregulated in MSS-LCLs. Tauroursodeoxycholic acid (TUDCA) attenuated ER stress-induced apoptosis. Conclusion MSS patient-derived cells exhibit increased ER stress, an activated UPR, and susceptibility to ER stress-induced death. TUDCA reduces ER stress-induced death of MSS patient-derived cells. The potential of TUDCA as a therapeutic agent for MSS could be explored further in preclinical studies.
- Published
- 2017
9. Spinocerebellar ataxia type 31 exists in Northeast China
- Author
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Liying Yuan, Ouyang Yi, Xue Qin, Zhiyi He, Lei Li, and Yinan Zhao
- Subjects
China ,Cerebellar ataxia ,Disease ,Middle Aged ,medicine.disease ,Neurology ,Autosomal dominant cerebellar ataxia ,Spinocerebellar ataxia ,medicine ,Humans ,Spinocerebellar Ataxias ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,Neuroscience ,Axonal sensorimotor neuropathy ,Spinocerebellar Degenerations - Abstract
Spinocerebellar ataxia type 31 (SCA31), is a recently defined subtype of autosomal dominant cerebellar ataxia (ADCA) characterized by late-onset pure cerebellar ataxia. SCA31 is common in Japan but whether or not it exists in other countries is still unclear. In this study, the authors describe a sporadic Chinese patient with SCA31. Although the cardinal clinical features, i.e., late-onset cerebellar ataxia and hearing impairment in our sporadic patient were similar to those described previously in Japan, mild axonal sensorimotor neuropathy was identified in our SCA31 patient, which is somewhat distinct from most prior reports of the disease. This is the first report of SCA31 in China; thus, extending the ethnic association beyond families of Japanese origin. In addition, our study suggests that the clinical features of SCA31 might be broader than previously thought.
- Published
- 2012
10. Identification of a new homozygous frameshift insertion mutation in the SIL1 gene in 3 Japanese patients with Marinesco–Sjögren syndrome
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Makoto Eriguchi, Yasuo Kuroda, Junko Fujitake, Kazuhiro Kurohara, and Haruo Mizuta
- Subjects
Adult ,Male ,DNA Mutational Analysis ,Marinesco–Sjögren syndrome ,medicine.disease_cause ,Frameshift mutation ,Exon ,Japan ,Cataracts ,medicine ,Guanine Nucleotide Exchange Factors ,Humans ,Insertion ,Frameshift Mutation ,Spinocerebellar Degenerations ,Genetics ,Mutation ,Cerebellar ataxia ,business.industry ,Homozygote ,Chromosome ,Exons ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,eye diseases ,digestive system diseases ,Neurology ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Marinesco-Sjögren syndrome (MSS) is an autosomal recessive multisystem disorder characterized by cerebellar ataxia, cataracts, progressive muscular weakness, and developmental and mental retardation. Recently, mutations in the SIL1 gene on chromosome 5q31 have been shown to be a cause of MSS. We sequenced the entire SIL1-coding region in 3 unrelated Japanese patients with classical MSS and identified a novel homozygous frameshift insertion mutation, 936_937insG, in exon 9 in all 3 patients.
- Published
- 2008
11. Common mitochondrial DNA and POLG1 mutations are rare in the Chinese patients with adult-onset ataxia on Taiwan
- Author
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Yi-Chun Lu, Bing-Wen Soong, Yi-Chung Lee, and Ming-Hon Chang
- Subjects
Adult ,Genetic Markers ,Male ,Mitochondrial DNA ,Ataxia ,Adolescent ,Genotype ,DNA Mutational Analysis ,Taiwan ,DNA-Directed DNA Polymerase ,Gene mutation ,Biology ,medicine.disease_cause ,DNA, Mitochondrial ,Asian People ,Predictive Value of Tests ,medicine ,Humans ,Spinocerebellar Ataxias ,Genetic Predisposition to Disease ,Genetic Testing ,Age of Onset ,Aged ,Spinocerebellar Degenerations ,Genetic testing ,Genetics ,Mutation ,medicine.diagnostic_test ,Cerebellar ataxia ,Point mutation ,Middle Aged ,medicine.disease ,DNA Polymerase gamma ,Neurology ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom - Abstract
Background and purpose: Spinocerebellar ataxia (SCA) is a heterogeneous group of neurodegenerative disorders with common features of adult-onset cerebellar ataxia. Many patients with clinically suspected SCA are subsequently diagnosed with common SCA gene mutations. Previous reports suggest some common mitochondrial DNA (mtDNA) point mutations and mitochondrial DNA polymerase gene (POLG1) mutations might be additional underlying genetic causes of cerebellar ataxia. We tested whether mtDNA point mutations A3243G, A8344G, T8993G, and T8993C, or POLG1 mutations W748S and A467Tare found in patients with adult-onset ataxia who did not have common SCA mutations. Methods: Four hundred seventy-six unrelated patients with suspected SCA underwent genetic testing for SCA 1, 2, 3, 6, 7, 8, 10, 12, 17, and DRPLA gene mutations. After excluding these SCA mutations and patients with paternal transmission history, 265 patients were tested for mtDNA mutations A3243G, A8344G, T8993G, T8993C, and POLG1 W748S and A467T mutations. Results: No mtDNA A3243G, A8344G, T8993G, T8993C, or POLG1 W748S and A467T mutation was detected in any of the 265 ataxia patients, suggesting that the upper limit of the 95% confidence interval for the prevalence of these mitochondrial mutations in Chinese patients with adult-onset non-SCA ataxia is no higher than 1.1%. Conclusions: The mtDNA mutations A3243G, A8344G, T8993G, T8993C, or POLG1 W748S and A467T are very rare causes of adultonset ataxia in Taiwan. Routine screening for these mutations in ataxia patients with Chinese origin is of limited clinical value. © 2007 Elsevier B.V. All rights reserved.
- Published
- 2007
12. Quantitative evaluation of gait ataxia by accelerometers
- Author
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Shinichi Shirai, Masaaki Matsushima, Mitsuru Yoneyama, Ichiro Yabe, Yoichi M. Ito, and Hidenao Sasaki
- Subjects
Adult ,Gait Ataxia ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Ataxia ,Cerebellar Ataxia ,Posture ,Walking ,the Scale for the Assessment and Rating of Ataxia (SARA) ,Severity of Illness Index ,Young Adult ,Gait (human) ,Physical medicine and rehabilitation ,Accelerometry ,medicine ,Postural Balance ,Humans ,Gait ,Aged ,Spinocerebellar Degenerations ,Aged, 80 and over ,Cerebellar ataxia ,Middle Aged ,quantitative evaluation ,accelerometer ,Neurology ,Berg Balance Scale ,Gait analysis ,gait analysis ,biomarker ,Biomarker (medicine) ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,human activities ,Biomarkers - Abstract
An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6 min of walking and 1 min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia.
- Published
- 2015
13. Late-onset pure cerebellar ataxia: Differentiating those with and without identifiable mutations
- Author
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Kevin A. Kerber, Susan Perlman, Joanna C. Jen, and Robert W. Baloh
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pathology ,medicine.medical_specialty ,Ataxia ,Late onset ,Biology ,Genetic analysis ,Nystagmus, Pathologic ,Diagnosis, Differential ,medicine ,Humans ,Family ,Age of Onset ,Family history ,Molecular Biology ,Aged ,Spinocerebellar Degenerations ,Genetics ,Cerebellar ataxia ,Genetic disorder ,Middle Aged ,medicine.disease ,FMR1 ,Neurology ,Oculomotor Muscles ,Fragile X Syndrome ,Mutation ,Female ,Neurology (clinical) ,medicine.symptom ,Age of onset - Abstract
Late onset cerebellar ataxia can be caused by several genetic mutations but a large percentage of patients remain undiagnosed. Thirty-eight patients with onset of slowly progressive, pure cerebellar ataxia >or=40 years-of-age were identified from a large ataxia database. Their clinical findings and quantitative oculomotor tests were reviewed; all were screened for SCA1, SCA2, SCA3, SCA6, SCA8, SCA14, and the Fragile X premutation (FMR1). All 47 exons of CACNA1A were screened for mutations. Genetic analysis uncovered a mutation in 11 patients. The SCA6 mutation was present in 8 patients (repeats 22-23). Three additional genetic mutations were found: SCA1 (42 repeats), SCA3 (66 repeats), and SCA8 (121 repeats). Patients without identified genetic mutations were characterized by 1) a later age of onset, 2) truncal without extremity ataxia, 3) and down beat nystagmus. Although only a third of these idiopathic late onset ataxia patients had a positive family history, this homogeneous syndrome probably represents a yet to be identified genetic disorder.
- Published
- 2005
14. Exome analysis reveals a Japanese family with spinocerebellar ataxia, autosomal recessive 1
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Yuji Takahashi, Ichiro Kanazawa, Yaeko Ichikawa, Jun Goto, Hiroyuki Ishiura, Shinichi Morishita, Koichiro Doi, Shoji Tsuji, Jun Yoshimura, Hiroshi Takuma, Shunsuke Kobayashi, and Jun Mitsui
- Subjects
Male ,Ataxia ,Genetic Linkage ,DNA Mutational Analysis ,Nonsense mutation ,Disease ,Polymorphism, Single Nucleotide ,Japan ,Genetic linkage ,Humans ,Spinocerebellar Ataxias ,Medicine ,Exome ,Exome sequencing ,Spinocerebellar Degenerations ,Family Health ,Genetics ,Massive parallel sequencing ,business.industry ,DNA Helicases ,medicine.disease ,Multifunctional Enzymes ,Neurology ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,business ,RNA Helicases - Abstract
Spinocerebellar ataxia autosomal recessive 1 (SCAR1/AOA2) is clinically characterized by an early-onset progressive cerebellar ataxia with axonal neuropathy, ocular motor apraxia, and elevation of serum alpha-fetoprotein level. The disorder is caused by mutations in senataxin (SETX) gene. Here, we report a Japanese SCAR1/AOA2 family with a homozygous nonsense mutation (p.Q1441X) of SETX that was identified by exome sequencing. The family was previously reported as early-onset ataxia of undetermined cause. The present study emphasized the role of whole exome-sequence analysis to establish the molecular diagnosis of neurodegenerative disease presenting with diverse clinical presentations.
- Published
- 2013
15. The aetiology of Idiopathic Late Onset Cerebellar Ataxia (ILOCA): Clinical and imaging clues for a definitive diagnosis
- Author
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Paulo Bugalho, Raquel Barbosa, and Tânia Lampreia
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Ataxia ,REM sleep behavior disorder ,Diagnosis, Differential ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Idiopathic late-onset cerebellar ataxia ,Pons ,Brain mri ,Humans ,Medicine ,Age of Onset ,Aged ,Retrospective Studies ,Spinocerebellar Degenerations ,business.industry ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,030104 developmental biology ,Neurology ,Disease Progression ,Etiology ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Neuroscience ,030217 neurology & neurosurgery - Published
- 2016
16. d-Cycloserine for the treatment of ataxia in spinocerebellar degeneration
- Author
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Mitsuru Kawai, Keiji Wada, Hiroshi Shigeto, Yasushi Oya, Toru Nishikawa, Toshiyuki Yamamoto, and Masafumi Ogawa
- Subjects
Adult ,Male ,Agonist ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Ataxia ,medicine.drug_class ,Walking ,Neuropsychological Tests ,Pharmacology ,Placebo ,Partial agonist ,Drug Administration Schedule ,Placebos ,Central nervous system disease ,medicine ,Humans ,Speech ,Single-Blind Method ,Antibiotics, Antitubercular ,Aged ,Spinocerebellar Degenerations ,Psychiatric Status Rating Scales ,Dose-Response Relationship, Drug ,Cycloserine ,Middle Aged ,medicine.disease ,Surgery ,Neurology ,Spinocerebellar ataxia ,Female ,International Cooperative Ataxia Rating Scale ,Neurology (clinical) ,medicine.symptom ,Psychology ,medicine.drug - Abstract
We studied the effects of d -cycloserine, a partial NMDA receptor allosteric agonist, on ataxia in patients with spinocerebellar degeneration. Fifteen Japanese ataxic patients enrolled in a 14-day single-blind trial of d -cycloserine (daily oral dose of 50 mg) following a 14-day single-blind placebo phase. At the end of the d -cycloserine administration, there was a significant reduction in the posture, gait and total score of the international cooperative ataxia rating scale and in the time for walking and speech tasks. d -Cycloserine was well-tolerated and no adverse effect was observed. d -Cycloserine may have therapeutic efficacy for spinocerebellar ataxia.
- Published
- 2003
17. Movement disorders in hereditary ataxias
- Author
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Pedro J Garcia Ruiz, S Cantarero, Carmen Ayuso, Hernández J, and David Mayo
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pediatrics ,Ataxia ,Movement disorders ,Adolescent ,Neurological disorder ,Central nervous system disease ,medicine ,Humans ,Vitamin E Deficiency ,Prospective Studies ,Child ,Aged ,Spinocerebellar Degenerations ,Aged, 80 and over ,Dystonia ,Movement Disorders ,business.industry ,Parkinsonism ,Chorea ,Machado-Joseph Disease ,Middle Aged ,Myoclonic Epilepsies, Progressive ,medicine.disease ,Surgery ,Neurology ,Friedreich Ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Myoclonus - Abstract
Movement disorders are well known features of some dominant hereditary ataxias (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan atrophy. However, little is known about the existence and classification of movement disorders in other dominant and recessive ataxias. We prospectively studied the presence of movement disorders in patients referred for HA over the last 3 years. Only those patients with a confirmed family history of ataxia were included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases of dominant HA. Thirty out of 46 cases of recessive HA could be classified as: Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8 cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with recessive HA, including 16 patients (16/29) with FA. In general, postural tremor was the most frequent observed movement disorder (27 cases), followed by dystonia (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several movement disorders coexisted. Movement disorders are frequent findings in HA, not only in dominant HA but also in recessive HA.
- Published
- 2002
18. Double-blind crossover study of branched-chain amino acid therapy in patients with spinocerebellar degeneration
- Author
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Yoshiki Adachi, Nozomi Mori, M. Mori, Takao Takeshima, Saiko Kurihara, Masayoshi Kusumi, Yoshihiro Kashiwaya, and Kenji Nakashima
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Ataxia ,Randomization ,Diet therapy ,Glutamic Acid ,Placebo ,Gastroenterology ,Double-Blind Method ,Cerebellum ,Internal medicine ,Humans ,Medicine ,Spinocerebellar ataxia type 6 ,Aged ,Spinocerebellar Degenerations ,Cross-Over Studies ,Dose-Response Relationship, Drug ,Cerebellar ataxia ,business.industry ,Recovery of Function ,Middle Aged ,medicine.disease ,Crossover study ,Surgery ,Treatment Outcome ,Neurology ,Synapses ,Female ,International Cooperative Ataxia Rating Scale ,Neurology (clinical) ,medicine.symptom ,business ,Amino Acids, Branched-Chain - Abstract
To determine whether treatment with branched-chain amino acids (BCAA) can improve the condition of patients with ataxia, a double-blind crossover study of BCAA therapy was performed in 16 patients with spinocerebellar degeneration (SCD). The patients were treated with BCAA in oral doses of 1.5, 3.0, or 6.0 g or with placebo daily for 4 weeks in each study phase. The order of treatment phases (placebo or BCAA) was assigned randomly. An International Cooperative Ataxia Rating Scale (ICARS) was used to quantify the severity of symptoms of SCD. The mean ICARS score improved significantly with BCAA treatment compared with the mean pretreatment score (p
- Published
- 2002
19. C9ORF72 repeat expansion is not a significant cause of late onset cerebellar ataxia syndrome
- Author
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Cheng-Tsung Hsiao, Yi-Chung Lee, Pei-Chien Tsai, Bing-Wen Soong, and Yi-Chu Liao
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Taiwan ,Polymerase Chain Reaction ,Cohort Studies ,Young Adult ,C9orf72 ,medicine ,Dementia ,Humans ,Genetic Predisposition to Disease ,Amyotrophic lateral sclerosis ,Aged ,Spinocerebellar Degenerations ,Genetics ,DNA Repeat Expansion ,Cerebellar ataxia ,C9orf72 Protein ,business.industry ,Proteins ,Middle Aged ,medicine.disease ,Neurology ,Mutation (genetic algorithm) ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,Trinucleotide repeat expansion ,business ,Frontotemporal dementia - Abstract
The GGGGCC hexanucleotide expansion in the C9ORF72 gene is the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasian populations. The phenotypic spectrum of C9ORF72 hexanucleotide repeat expansion mutation has been reported to include parkinsonian syndrome, Huntington's disease-like syndrome and dementia syndrome. Although few individuals with cerebellar ataxia have also anecdotally been found to harbor the mutation, the relationship between the mutation and cerebellar ataxia awaits further clarification. We hereby screened for the presence of the C9ORF72 hexanucleotide repeat expansion in 331 patients with multiple system atrophy-cerebellar variant and 98 unrelated patients with molecularly un-assigned spinocerebellar ataxia in Taiwan utilizing a repeat-primed polymerase chain reaction assay. We found that none of the 429 patients had the C9ORF72 hexanucleotide repeat expansion mutation. Therefore, our study does not support that the mutation plays a significant role in cerebellar ataxia.
- Published
- 2014
20. Reduced pre-movement facilitation of motor evoked potentials in spinocerebellar degeneration
- Author
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Takao Takeshima, Takashi Nomura, and Kenji Nakashima
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,medicine.medical_treatment ,Pyramidal Tracts ,Stimulation ,Thumb ,Central nervous system disease ,Magnetics ,Physical medicine and rehabilitation ,Cerebellum ,Neural Pathways ,Reaction Time ,medicine ,Humans ,Evoked potential ,Aged ,Spinocerebellar Degenerations ,Movement Disorders ,Cerebellar ataxia ,Motor Cortex ,Middle Aged ,Evoked Potentials, Motor ,medicine.disease ,Electric Stimulation ,Transcranial magnetic stimulation ,medicine.anatomical_structure ,Neurology ,Cerebral cortex ,Spinocerebellar Tracts ,Facilitation ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,Neuroscience - Abstract
Objectives: The aim of this study was to clarify the cerebellar effects on the motor area of the cerebral cortex and abnormal control mechanisms of voluntary movement in spinocerebellar degeneration (SCD). We used transcranial magnetic stimulation (TMS) to study the change in the motor evoked potentials (MEPs) before voluntary movement (pre-movement facilitation) in patients with SCD. Subjects and methods: Pre-movement facilitation of MEPs in subjects' muscles was observed during their thumb movement intention. Patients with SCD, who showed cerebellar signs, without pyramidal or extrapyramidal signs, were examined. TMS was applied randomly during the interval between the "go" signal and the onset of voluntary EMG. The MEPs were recorded from the abductor brevis pollicis muscle. Results: Patients with SCD showed a delay of task performance. In control subjects, the amplitude of MEPs was significantly facilitated (increased) prior to voluntary movement. In patients with SCD, pre-movement facilitation of the amplitude of MEPs was significantly decreased in the study with subthreshold TMS. Conclusions: Disturbance of pre-movement facilitation in SCD may indicate incomplete cerebellar regulation of voluntary movements.
- Published
- 2001
21. Asymptomatic CTG expansion at the SCA8 locus is associated with cerebellar atrophy on MRI
- Author
-
Mikio Shoji, Koichi Okamoto, Michèle Schmitt, Mitsunori Watanabe, Yoshio Ikeda, and Masami Shizuka-Ikeda
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pathology ,medicine.medical_specialty ,Ataxia ,Biology ,medicine ,Humans ,Spinocerebellar Ataxias ,Aged ,Spinocerebellar Degenerations ,Cerebellar ataxia ,medicine.disease ,Magnetic Resonance Imaging ,Penetrance ,Pedigree ,Neurology ,Mutation ,Spinocerebellar ataxia ,Dynamic mutation ,Cerebellar vermis ,Female ,Cerebellar atrophy ,Neurology (clinical) ,medicine.symptom ,Trinucleotide Repeat Expansion ,Trinucleotide repeat expansion - Abstract
Spinocerebellar ataxia type 8 (SCA8) is the first example of dominantly inherited ataxia reported to be caused by a dynamic mutation of the untranslated CTG trinucleotide repeat. We performed genetic and clinical analyses of a family with an isolated case with young onset cerebellar ataxia carrying an expanded 95 CTA/CTG repeats, and revealed that the asymptomatic father was also carrying a much greater expansion of 136 repeats. This paternal transmission developed a large contraction of -41 CTG repeats. The ataxia patient showed almost pure cerebellar symptoms, and a cerebral MRI of the patient demonstrated significant atrophy of the cerebellar vermis and hemispheres with preservation of brainstem and cerebrum. Although the father did not show any neurological abnormalities, his MRI demonstrated mild atrophy of the cerebellar hemispheres. The genetic phenomenon on this family has not been observed in other types of SCAs, and this reduced penetrance may cause reproduction of sporadic SCA8 frequently. Therefore, we must perform careful interviews regarding family history, and suggest the genetic and neuroradiological investigations on family members when we encounter a sporadic patient with the CTG expansion at the SCA8 locus.
- Published
- 2000
22. Early-onset progressive ataxia associated with the first CACNA1A mutation identified within the I–II loop
- Author
-
Carlo Casali, Francesco Pierelli, C. Di Lorenzo, Alessio Cardinale, G. Nappi, C. Rengo, Federica Cricchi, G. S. Grieco, Filippo M. Santorelli, and M. Racaniello
- Subjects
Genetic Markers ,Male ,Cerebellum ,medicine.medical_specialty ,Ataxia ,Genotype ,DNA Mutational Analysis ,Internal medicine ,medicine ,Humans ,Point Mutation ,Spinocerebellar ataxia type 6 ,Genetic Predisposition to Disease ,Genetic Testing ,Age of Onset ,Carbonic Anhydrase Inhibitors ,Familial hemiplegic migraine ,Spinocerebellar Degenerations ,Cerebellar ataxia ,business.industry ,Exons ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Pedigree ,Acetazolamide ,Treatment Outcome ,medicine.anatomical_structure ,Endocrinology ,Amino Acid Substitution ,Neurology ,Disease Progression ,Female ,Cerebellar atrophy ,Calcium Channels ,Neurology (clinical) ,medicine.symptom ,Age of onset ,business ,Neuroscience - Abstract
Familial hemiplegic migraine type 1, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) are allelic disorders associated with mutations in the CACNA1A gene, which encodes the alpha1 subunit of the P/Q-type calcium channel (Ca(V)2.1). SCA6 and EA2 share a number of clinical features, such as prominent cerebellar involvement and good response to acetazolamide therapy. However, while SCA6 develops as a late-onset, progressive ataxia, EA2 has an earlier, and episodic, onset. We report on two sisters with a heterogeneous clinical phenotype. The first developed progressive cerebellar ataxia after age 30, without noticeable episodes of vertigo or headache. A 1 year trial with acetazolamide did not produce significant results. The other reported episodes of vertigo, headache and gait imbalance since late childhood, with good response to acetazolamide, before developing moderate chronic cerebellar ataxia. Brain MRI showed cerebellar atrophy, especially in the vermis, in both patients. Direct sequencing of CACNA1A identified a heterozygous 1360G>A mutation in exon 11 resulting in the substitution of alanine for threonine at residue 454 (p.Ala454Thr). This is the first description of a change residing in the cytoplasmic I-II loop associated with a clinical phenotype.
- Published
- 2007
23. Letter to the Editor on a paper by Hsiao C-T, Tsai P-C, Liao Y-C, Lee Y-C, Soong B-W. C9ORF72 repeat expansion is not a significant cause of late-onset cerebellar ataxia syndrome. J Neurol Sci 2014;347:322–324
- Author
-
Jean Pouget, Annabelle Chaussenot, Véronique Paquis-Flucklinger, Cécile Rouzier, Samira Ait-El-Mkadem, Gaëlle Augé, Emmanuelle C. Genin, Sylvie Bannwarth, Sabrina Sacconi, and Morgane Plutino
- Subjects
Male ,DNA Repeat Expansion ,Letter to the editor ,Cerebellar ataxia ,Late-onset cerebellar ataxia ,Mitochondrial disease ,Proteins ,Anatomy ,Biology ,medicine.disease ,Neurology ,C9orf72 ,medicine ,Humans ,Female ,Neurology (clinical) ,medicine.symptom ,Trinucleotide repeat expansion ,Neuroscience ,Spinocerebellar Degenerations - Published
- 2015
24. A Japanese family with spinocerebellar ataxia type 6 which includes three individuals homozygous for an expanded CAG repeat in the SCA6/CACNL1A4 gene
- Author
-
Masatoyo Nishizawa, Kin Ya Ishikawa, Eisaku Esumi, Yoshihisa Takiyama, Kumi Sakoe, Michiyo Soutome, T. Ogawa, Imaharu Nakano, Hidehiro Mizusawa, and Michito Namekawa
- Subjects
Male ,Ataxia ,Biology ,Genetic determinism ,Degenerative disease ,Japan ,Genotype ,medicine ,Humans ,Spinocerebellar ataxia type 6 ,Aged ,Repetitive Sequences, Nucleic Acid ,Spinocerebellar Degenerations ,Aged, 80 and over ,Genetics ,Base Sequence ,Cerebellar ataxia ,Homozygote ,Brain ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Pedigree ,Neurology ,Anticipation (genetics) ,Spinocerebellar ataxia ,Female ,Calcium Channels ,Neurology (clinical) ,medicine.symptom - Abstract
We describe a Japanese family which includes 13 patients in five generations who have dominantly inherited ataxia. Molecular testing revealed that in these patients the SCA6/CACNL1A4 gene carries the smallest known expanded CAG repeat (21 repeat units). The clinical features of these patients exhibited predominantly cerebellar ataxia with onset late in adult life and a very slowly progressive disease course. In addition, this SCA6 family showed some characteristic clinical and genetic features, including (1) apparent lack of genetic anticipation, with an intergenerationally stable CAG repeat size and (2) down-beat nystagmus and diabetes mellitus in some of the SCA6 patients. We identified three individuals homozygous for an expanded CAG repeat (21/21) in the SCA6/CACNL1A4 gene, two of whom were symptomatic. There were no apparent differences in clinical phenotype between the individuals homozygous and those heterozygous for an expanded CAG repeat in the SCA6/CACNL1A4 gene.
- Published
- 1998
25. Hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA): Clinical and neuropathological features of a Japanese family
- Author
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S Nakagawa, Ken-ichi Tabata, H Ishigame, Shinji Ohara, Kunihiro Yoshida, Yoshiki Sekijima, Nobuo Yanagisawa, and Y Shimizu
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Cerebellum ,Cerebellar Ataxia ,Genes, Recessive ,Hyperlipidemias ,Purkinje Cells ,Atrophy ,Japan ,medicine ,Humans ,Peripheral Nerves ,Age of Onset ,Serum Albumin ,Spinocerebellar Degenerations ,Movement Disorders ,Spinocerebellar tract ,business.industry ,Syndrome ,Middle Aged ,medicine.disease ,Spinal cord ,Amyotrophy ,Magnetic Resonance Imaging ,Pedigree ,medicine.anatomical_structure ,nervous system ,Neurology ,Nerve Degeneration ,Disease Progression ,Dementia ,Female ,Cerebellar atrophy ,Neurology (clinical) ,Hereditary Sensory and Motor Neuropathy ,business ,Hereditary motor and sensory neuropathy ,Neuroscience ,Polyneuropathy ,Demyelinating Diseases - Abstract
We report clinicopathological features of a Japanese family with hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA). Four affected members from a single generation were examined. They shared common clinical features, including insidious onset in teenage, slowly progressive cerebellar ataxia, amyotrophy, sensory disturbance, and dementia. In addition, all the patients showed hypoalbuminemia and hyperlipidemia and a marked atrophy of the cerebellum on magnetic resonance images. Autopsy of the proband revealed a severe loss of Purkinje cells, degeneration of posterior columns and spinocerebellar tracts of the spinal cord, and a marked loss of myelinated and unmyelinated fibers in the peripheral nerves. We consider that HMSNCA is a distinct form of hereditary multisystem neuronal degeneration.
- Published
- 1998
26. Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG trinucleotide expansion and clinical characteristics
- Author
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Yasuto Itoyama, Mitsunori Watanabe, Koichi Okamoto, Masami Shizuka, Kazuyuki Mizushima, Masashi Aoki, Mikio Shoji, and Koji Abe
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Spinocerebellar Ataxia Type 1 ,medicine.medical_specialty ,Pathology ,Adolescent ,Population ,Biology ,Japan ,Trinucleotide Repeats ,Internal medicine ,medicine ,Humans ,Spinocerebellar ataxia type 6 ,Child ,education ,Spinocerebellar Degenerations ,education.field_of_study ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Hypotonia ,nervous system diseases ,Phenotype ,Endocrinology ,Neurology ,Anticipation (genetics) ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,Trinucleotide repeat expansion - Abstract
We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven unrelated families who live in Gunma Prefecture, Japan (population approx. 2,000,000), and documented the clinical and molecular properties correlated with the CAG repeat expansion. Twelve of the 13 patients and one presymptomatic female were genetically examined, and the CAG repeat number of the expanded and normal alleles was 40.8+/-4.8 (mean+/-S.D., n=13) and 22+/-0 (n=13), respectively. The repeat size of the expanded alleles was inversely correlated with the patients' age at onset. Paternal anticipation was observed, accompanied by an increase of the CAG repeat size. The patients presented here were clinically characterized by a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and tremor. A number of peaks in the expanded allele on polyacrylamide gel electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are almost equally present and at higher frequencies than spinocerebellar ataxia type 1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the difference of frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.
- Published
- 1998
27. Autosomal dominant cerebellar ataxia deafness and narcolepsy
- Author
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Jerker Hetta, Per Olov Lundberg, Atle Melberg, Mats Bengtsson, Karl Henrik Gustavson, Inger Nennesmo, Niklas Dahl, Crawford Grant, and Rolf Wibom
- Subjects
Male ,Spinocerebellar Ataxia Type 1 ,Pathology ,medicine.medical_specialty ,Ataxia ,Adolescent ,Neurological disorder ,Deafness ,In Vitro Techniques ,Atrophy ,Autosomal dominant cerebellar ataxia ,medicine ,Humans ,Genes, Dominant ,Narcolepsy ,Spinocerebellar Degenerations ,Muscle biopsy ,Base Sequence ,medicine.diagnostic_test ,Cerebellar ataxia ,Middle Aged ,medicine.disease ,Pedigree ,Neurology ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,Neuroscience - Abstract
A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.
- Published
- 1995
28. Spinocerebellar ataxia, type 3 (SCA3) is genetically identical to Machado-Joseph disease (MJD)
- Author
-
Ulrich Müller, Maxwell S. Damian, Gerd Haberhausen, and Frank Leweke
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.disease_cause ,Degenerative disease ,Autosomal dominant cerebellar ataxia ,medicine ,Humans ,Gene ,Genes, Dominant ,Repetitive Sequences, Nucleic Acid ,Spinocerebellar Degenerations ,Chromosomes, Human, Pair 14 ,Genetics ,Mutation ,Chromosome Mapping ,Chromosome ,Machado-Joseph Disease ,Middle Aged ,medicine.disease ,Pedigree ,Neurology ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,Trinucleotide repeat expansion ,Psychology ,Machado–Joseph disease - Abstract
Spinocerebellar ataxia, type 3 (SCA3) and Machado-Joseph disease (MJD) are two clinically distinct representatives of the heterogeneous group of autosomal dominant cerebellar ataxias. Assignment of the disease genes to the same region of the long arm of chromosome 14 in both SCA3 and MJD suggested that these two disorders are genetically identical. The recent identification of a trinucleotide (CAG) repeat expansion in a gene underlying MJD facilitates assessment of this hypothesis. We analysed the MJD gene in members of a family with characteristic features of SCA3 and no symptoms typical of MJD. We found the same trinucleotide repeat expansion within the gene that was previously described in patients with MJD. The findings demonstrate that SCA3 and MJD are genetically identical in spite of their pronounced clinical differences. Furthermore, we demonstrate a striking variation in the copy number of the CAG repeat among affected members of the same family.
- Published
- 1995
29. Autosomal recessive ataxia, slow eye movements and psychomotor retardation
- Author
-
Abdul-Latif Wriekat, Majed Dasouki, Amar Mubaidin, Mohammed S. Al-Khateeb, Amir S. Najim Al-Din, Ashraf Al-Kurdi, and Mohmad Al-Hiari
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ataxia ,Eye disease ,Genes, Recessive ,Audiology ,Central nervous system disease ,Ocular Motility Disorders ,Degenerative disease ,Saccades ,medicine ,Humans ,Spinocerebellar Degenerations ,Jordan ,Psychomotor retardation ,medicine.disease ,Magnetic Resonance Imaging ,eye diseases ,Pedigree ,Neurology ,Female ,Neurology (clinical) ,Psychomotor Disorders ,medicine.symptom ,Tomography, X-Ray Computed ,Psychology ,Psychomotor disorder ,Neuroscience - Abstract
Two consanguineous Arab families with an autosomal recessive form of hereditary ataxia with slow eye movements and psychomotor retardation are reported. The ataxia presented in the first decade, was severely disabling and was associated with a spectrum of eye movements abnormalities as well as psychomotor retardation and sensory neuropathy. MRI studies of the brain showed a significant degree of cerebellar and brainstem atrophy. These 2 families support a previous report of a similarly affected consanguineous Arab family. The syndrome of autosomal recessive ataxia and slow or even absent saccades is proposed to be related but not identical to the autosomal dominant form known as the Wadia Swami syndrome, both of which seem to be related to the olivopontocerebellar degenerations.
- Published
- 1994
30. Uses of the postural stability test for differential diagnosis of hereditary ataxias
- Author
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V. Komarek, Pavel Hrasky, Frantisek Zahalka, O. Cakrt, J. Schwabova, Alena Zumrová, Tomas Maly, and Tomáš Gryc
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ataxia ,Adolescent ,Posture ,Diagnostic Techniques, Neurological ,Audiology ,Diagnosis, Differential ,Young Adult ,Sensory ataxia ,Sensation ,medicine ,Humans ,Spinocerebellar Ataxias ,Postural Balance ,Czech Republic ,Spinocerebellar Degenerations ,Cerebellar ataxia ,Posturography ,Middle Aged ,medicine.disease ,Hereditary Ataxias ,Neurology ,Friedreich Ataxia ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,Differential diagnosis ,Psychology ,Psychomotor Performance - Abstract
Friedreich's ataxia (FRDA) and spinocerebellar ataxia type 2 (SCA 2) are among the most commonly diagnosed hereditary ataxias in Czech Republic. Although criteria differentiate the ataxias, disorder onset symptoms may be similar. Our goal was to determine whether and to what degree of validity posturographic examination may be utilized, with the aim of differential diagnosis; which specific posturographic parametres are suitable for differential diagnosis; and which differences in FRDA and SCA 2 patient posturographic findings may be established. 17 SCA 2 and 12 FRDA patients were examined with ten healthy controls. A multi-sensor tenzometric platform was used for posturographic examination. Toe standing position was added to basic tests, including standing position with and without visual control. There was no difference between patients in standing position with visual control but there were distinct differences between FRDA and SCA 2 patients, based on upright stance without visual control and medio-lateral deviation. There were no differences between patients in toe standing position, suggesting not only the cerebellum, but also deep sensation, helps to create the so-called adaptive controller. Posturography is attested to as a useful method for differential diagnosis of hereditary ataxias and provides neurophysiological findings in cerebellar and sensoric ataxias.
- Published
- 2011
31. Chronic progressive spinocerebellar syndrome associated with antibodies to human T-lymphotropic virus type I: clinico-virological and magnetic resonance imaging studies
- Author
-
Jun Ichi Kira, Yuichi Ichiya, Makoto Otsuka, and Ikuo Goto
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Cerebellum ,Pathology ,medicine.medical_specialty ,viruses ,Leukoencephalopathy ,White matter ,Myelopathy ,immune system diseases ,hemic and lymphatic diseases ,Reflex ,Tropical spastic paraparesis ,medicine ,Humans ,Aged ,Spinocerebellar Degenerations ,Movement Disorders ,business.industry ,Brain ,virus diseases ,Middle Aged ,medicine.disease ,HTLV-I Infections ,Magnetic Resonance Imaging ,Hyperintensity ,medicine.anatomical_structure ,Autonomic Nervous System Diseases ,Neurology ,Htlv i associated myelopathy ,Female ,Cerebellar atrophy ,Neurology (clinical) ,business - Abstract
The relationship between HTLV-I infection and the development of spinocerebellar degeneration (SCD) in adulthood was studied. The frequency of anti-HTLV-I antibodies among patients with SCD (8 of 43, 19%) was found to be higher than the seroprevalence rate in the northern part of Kyushu island (6%). All HTLV-I carriers with SCD showed chronic progressive cerebellar ataxia as a predominant feature and cerebellar atrophy was evident in 6 of 8 patients on magnetic resonance imaging (MRI) of the brain. However, SCD patients with anti-HTLV-I antibodies showed a significantly higher frequency of cerebral white matter lesions on brain MRI (6 of 8) and pyramidal tract signs in lower extremities (6 of 8) than did those without the antibodies (35%, P < 0.05 and 26%, P < 0.01, respectively). Moreover, the HTLV-I carriers with SCD exceeded 14 HTLV-I carriers having neither SCD nor HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) (21%, P < 0.05), and 59 HTLV-I seronegative patients without brain disorders (19%, P < 0.001) in the frequency of white matter lesions. On the other hand, the HTLV-I carriers with SCD were distinct to the HAM/TSP patients in the predominance of cerebellar involvement. Therefore, the peculiar features of cerebellar, pyramidal and white matter involvement in the HTLV-I-seropostive SCD patients as well as the increased frequency of HTLV-I infection among SCD patients suggest that this syndrome may be a distinct subtype of HTLV-I-associated neurologic diseases.
- Published
- 1993
32. Pathology of the cerebellar dentate and interpositus nuclei in Joseph disease: a morphometric investigation
- Author
-
Yuken Fukutani, K. Kobayashi, Nariyoshi Yamaguchi, Ichiro Nakamura, and Rokuro Matsubara
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Joseph Disease ,Efferent ,Cell number ,Cell Count ,Biology ,Degenerative disease ,Cerebellar hemisphere ,medicine ,Humans ,Spinocerebellar Degenerations ,Neurons ,Cell Death ,Anatomy ,medicine.disease ,Control subjects ,Dentate nucleus ,medicine.anatomical_structure ,Cerebellar Nuclei ,nervous system ,Neurology ,Nerve Degeneration ,Female ,Neurology (clinical) ,Nucleus - Abstract
Cerebellar dentate and interpositus nuclei pathology was studied morphometrically in 3 patients with Joseph disease compared to 3 control subjects. Size of neurons, number of small neurons (cell body area: 50-199 microns 2) and large neurons (cell body area: 200 microns 2 or greater) at the rostral, medial and caudal levels, neuronal cell density, total volume of the gray bands, and total neuronal cell number were evaluated in the dentate, emboliform, and globose nuclei, using an image analyzer, after making horizontal serial 20-microns thick sections of a unilateral cerebellar hemisphere embedded in celloidin. The number of large neurons in Joseph disease was around 20% of that in the controls at each level in the individual nucleus (P less than 0.05 or P less than 0.01). In contrast, the number of small neurons was significantly reduced only at the caudal level of the dentate nucleus (P less than 0.05). The neuronal cell density was decreased within the nuclei. The total volume of the gray bands was reduced to about 70% within the nuclei (P less than 0.05 or P less than 0.01). The total number of neurons was decreased to about a third, a half, and a third within the dentate (P less than 0.001), emboliform (P less than 0.01), and globose nuclei (P less than 0.001), respectively. The principal pathologic change of the dentate and interpositus nuclei in Joseph disease was severe loss of neurons, with significant loss of the large neurons, indicating that Joseph disease is a type of cerebellar efferent system disorder.
- Published
- 1992
33. Spinocerebellar variant of adrenoleukodystrophy with a novel ABCD1 gene mutation
- Author
-
Chi-Ren Tsai, Jie-Yuan Li, and Chia-Chi Hsu
- Subjects
Proband ,Adult ,Genetic Markers ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Genotype ,DNA Mutational Analysis ,Taiwan ,Gene mutation ,ATP Binding Cassette Transporter, Subfamily D, Member 1 ,Spinal Cord Diseases ,Exon ,Asian People ,Cerebellar Diseases ,Internal medicine ,Cerebellum ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Adrenoleukodystrophy ,Child ,Spinocerebellar Degenerations ,Genetics ,Cerebellar ataxia ,business.industry ,Leukodystrophy ,Exons ,medicine.disease ,Magnetic Resonance Imaging ,nervous system diseases ,Pedigree ,Endocrinology ,Neurology ,Spinal Cord ,Mutation ,Spinocerebellar ataxia ,ATP-Binding Cassette Transporters ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Gene Deletion - Abstract
X-linked adrenoleukodystrophy (X-ALD) shows a wide range of phenotypic expression, and clinical presentation as adult-onset spinocerebellar ataxia has been rarely reported. Here, we report a Taiwanese family with X-ALD. The proband, a 37-year-old man presented with dysarthria, cerebellar ataxia and mild spastic paraparesis, and had atrophy of cerebellum and upper cervical cord on MRI. One of his nephews, a 9-year-old boy had a classic childhood cerebral ALD phenotype. This family harbors a novel deletion of 1 base pair in exon 8 at nucleotide position 2245 (2245delA) in the ABCD1 gene. This is the first report of the 2245delA mutation presenting with a spinocerebellar variant of X-ALD.
- Published
- 2009
34. Evaluation of the effect of thyrotropin releasing hormone (TRH) on regional cerebral blood flow in spinocerebellar degeneration using 3DSRT
- Author
-
Ryuki Arakawa, Toshihide Kumamoto, Noriyuki Kimura, Takuya Hanaoka, Teruaki Masuda, Yuki Nomura, Yusuke Hazama, and Toshio Okazaki
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Cerebellum ,Thyrotropin-releasing hormone ,Hemodynamics ,Perfusion scanning ,Patlak plot ,Severity of Illness Index ,Internal medicine ,mental disorders ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Thyrotropin-Releasing Hormone ,Aged ,Spinocerebellar Degenerations ,Tomography, Emission-Computed, Single-Photon ,Electronic Data Processing ,Cerebellar ataxia ,Brain ,Middle Aged ,Hormones ,nervous system diseases ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Neurology ,Cerebral blood flow ,Regional Blood Flow ,Cerebrovascular Circulation ,Injections, Intravenous ,Cardiology ,Regression Analysis ,International Cooperative Ataxia Rating Scale ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,hormones, hormone substitutes, and hormone antagonists - Abstract
Thyrotropin releasing hormone (TRH) therapy improves cerebellar ataxia in patients with spinocerebellar degeneration (SCD). We investigated the effect of TRH on regional cerebral blood flow (rCBF) using the fully automated region of interest (ROI) technique, 3DSRT. Ten patients with SCD received TRH intravenously (2 mg/day) for 14 days and underwent brain perfusion single photon emission computed tomography before and after therapy. Clinical efficacy was assessed using the International Cooperative Ataxia Rating Scale (ICARS). The rCBF in each ROI was measured using the noninvasive Patlak plot method and calculated using 3DSRT. TRH significantly improved the ICARS scores and increased rCBF in the callosomarginal segment and cerebellum. Cerebellar rCBF increased in 4 of 5 patients with improved ICARS scores and in 3 of 5 patients without improved ICARS scores after TRH therapy. The correlation between the change in cerebellar rCBF and the improved ICARS score, however, was not significant. These findings indicate that TRH therapy may increase cerebellar rCBF in some patients with cerebellar forms of SCD and that 3DSRT may be useful for evaluating the efficacy of TRH for increasing CBF. The beneficial effects of TRH may be due to increased cerebellar rCBF or the increased rCBF may be a secondary effect of TRH therapy.
- Published
- 2008
35. Molecular analysis of a de novo mutation for spinocerebellar ataxia type 6 and (CAG)n repeat units in normal elder controls
- Author
-
Masami Shizuka, Yoshio Ikeda, Mitsunori Watanabe, Koichi Okamoto, Kazuyuki Mizushima, and Mikio Shoji
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,DNA Mutational Analysis ,Biology ,medicine.disease_cause ,Genetic determinism ,Degenerative disease ,Reference Values ,mental disorders ,medicine ,Humans ,Spinocerebellar ataxia type 6 ,Allele ,Repeated sequence ,Gene ,Aged ,Repetitive Sequences, Nucleic Acid ,Spinocerebellar Degenerations ,Genetics ,Mutation ,medicine.disease ,Pedigree ,nervous system diseases ,Neurology ,Anticipation (genetics) ,Female ,Neurology (clinical) - Abstract
Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant spinocerebellar degenerative disease caused by CAG repeat expansions in the human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4). We analyzed 15 SCA6 patients in 14 unrelated Japanese families and 52 healthy Japanese aged over 74 years. Sequence analysis was performed to determine the correct number of CAG repeats. The expanded CAG repeat number was 23.6+/-2.1 (mean+/-S.D., n=15) with a range of 20-29, and the shortest expanded allele was 20 repeats. Moreover, the analysis of normal subjects revealed that the CAG repeat number of normal alleles was 12.3+/-1.9 (n=104) with a range of 7-18. We concluded that the normal range of CAG repeats in the CACNL1A4 gene is 18 or less, and that the disease range is 20 or more. Of 15 SCA6 patients, three sporadic cases were observed. In one male patient with 26 CAG repeats, the CAG repeat numbers of his parents were within normal range. His expanded allele was considered to be caused by an expansion of a normal allele from his mother (14 or 17 repeats). This is the first SCA6 case which was genetically proven to occur due to a de novo mechanism, suggesting that larger CAG repeats of normal alleles in the CACNL1A4 gene may be unstable and result in full expansion.
- Published
- 1998
36. Downbeat nystagmus in two siblings with spinocerebellar ataxia type 6 (SCA 6)
- Author
-
Shin'ichi Shoji, Masahiko Watanabe, Kinnya Ishikawa, Akira Tamaoka, and Hirotsugu Harada
- Subjects
Adult ,Male ,Nystagmus, Pathologic ,Downbeat nystagmus ,Central nervous system disease ,Degenerative disease ,Trinucleotide Repeats ,Cerebellum ,medicine ,Humans ,Spinocerebellar ataxia type 6 ,Familial hemiplegic migraine ,Spinocerebellar Degenerations ,business.industry ,Episodic ataxia type 2 ,DNA ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Neurology ,Vertical nystagmus ,Female ,Calcium Channels ,Neurology (clinical) ,Atrophy ,business ,Neuroscience - Abstract
We report two siblings with spinocerebellar ataxia type 6 (SCA 6), both showing downbeat nystagmus (DBN) as a predominant clinical feature. Familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA-2) and SCA 6 are allelic disorders, and interestingly, the occasional presence of DBN in EA-2 was reported. Our observations suggest that common molecular mechanisms might underlie DBN in FHM, EA-2 and SCA 6. Then, these disorders should be kept in mind in diagnosing patients with DBN.
- Published
- 1998
37. Evaluation of brain perfusion SPECT using an easy Z-score imaging system (eZIS) as an adjunct to early-diagnosis of neurodegenerative diseases
- Author
-
Tatsuo Yamada, Hiroshi Matsuda, and Masaaki Waragai
- Subjects
Adult ,Lewy Body Disease ,Male ,Precuneus ,Diagnosis, Differential ,Gyrus ,Alzheimer Disease ,Predictive Value of Tests ,Cortex (anatomy) ,mental disorders ,Image Processing, Computer-Assisted ,Medicine ,Humans ,Aged ,Spinocerebellar Degenerations ,Tomography, Emission-Computed, Single-Photon ,Brain Mapping ,business.industry ,Dementia with Lewy bodies ,Amyotrophic Lateral Sclerosis ,Brain ,Neurodegenerative Diseases ,Parkinson Disease ,Frontal gyrus ,Middle Aged ,Multiple System Atrophy ,medicine.disease ,nervous system diseases ,medicine.anatomical_structure ,Early Diagnosis ,nervous system ,Neurology ,Posterior cingulate ,Cerebrovascular Circulation ,Cerebellar atrophy ,Dementia ,Female ,Neurology (clinical) ,business ,Occipital lobe ,Neuroscience - Abstract
The eZIS allows computer-assisted statistical analysis of brain perfusion SPECT images. We evaluated the diagnostic value of brain perfusion SPECT using eZIS in patients with various neurodegenerative diseases at a very early stage, within one year from onset. Methods SPECT using eZIS was performed for patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD,), idiopathic Parkinson disease (PD) and vascular Parkinsonism (VP), multiple systemic atrophy of the cerebellar type (MSA-C), cortical cerebellar atrophy (CCA) and amyotrophic lateral sclerosis (ALS). Results Decreased rCBF was observed in the posterior cingulate cortex, precuneus and parietal cortex in AD; in the frontal gyrus and insula in FTD; in the occipital lobe, precuneus gyrus and posterior cingulate cortex in DLB; in the striatum and the thalamus in VP; in the cerebellum in CCA; in the cerebellum and pons in MSA-C and in the frontal cortex including the central sulcus in ALS. Increased rCBF in the striatum, thalamus and cerebellar dentate nuclei were observed in PD. Conclusions A specific rCBF pattern was observed for each disease using eZIS analysis, consistent with previous reports. Our results showed eZIS can be easily used as an adjunct to early-diagnosis of neurodegenerative diseases in any hospital.
- Published
- 2006
38. A Japanese family with early-onset ataxia with motor and sensory neuropathy
- Author
-
Masaki Sakurai, Shigeo Murayama, Shunsuke Kobayashi, Hiroshi Takuma, and Ichiro Kanazawa
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Cerebellum ,Ataxia ,Genotype ,Glutamic Acid ,Genes, Recessive ,Neurological disorder ,Nerve Fibers, Myelinated ,Central nervous system disease ,Atrophy ,Japan ,Cerebellar hemisphere ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Peripheral Nerves ,Age of Onset ,Spinocerebellar Degenerations ,business.industry ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Surgery ,Pedigree ,Up-Regulation ,Peripheral neuropathy ,medicine.anatomical_structure ,Neurology ,Disease Progression ,Cerebellar atrophy ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Hereditary Sensory and Motor Neuropathy - Abstract
We report the case of a Japanese family with hereditary ataxia with peripheral neuropathy. Three affected siblings from this family exhibited very similar clinical features: teenage-onset, slowly progressive ataxia, followed by distal weakness, which developed after the age of 30 years. Magnetic resonance imaging studies showed marked atrophy in the cerebellar hemisphere and vermis, and a sural nerve biopsy revealed a marked reduction in the number of both myelinated and unmyelinated fibers. All patients exhibited hyperglutamatemia, but serum levels of albumin and lipid were normal. The clinicopathological and biochemical features of these cases suggest that they form a distinct entity of autosomal recessive hereditary ataxia with peripheral neuropathy.
- Published
- 2006
39. Novel compound heterozygous mutations in sacsin-related ataxia
- Author
-
Yoshihisa Takiyama, Haruo Shimazaki, Mutsuko Araki, Kotaro Hiraoka, Yoichi Yamamoto, S. Sakoda, and Seiichi Nagano
- Subjects
Adult ,Heterozygote ,Ataxia ,education ,DNA Mutational Analysis ,Genes, Recessive ,Compound heterozygosity ,medicine.disease_cause ,Japan ,Cerebellum ,Medicine ,Humans ,Genetic Testing ,Gene ,Amenorrhea ,Heat-Shock Proteins ,Early onset ,Spinocerebellar Degenerations ,Genetics ,Chromosome Aberrations ,Mutation ,High prevalence ,Chromosomes, Human, Pair 13 ,business.industry ,Twins, Monozygotic ,Pedigree ,Neurology ,Spinal Cord ,Muscle Spasticity ,French canadian ,Female ,Neurology (clinical) ,Spastic ataxia ,medicine.symptom ,Atrophy ,business - Abstract
High prevalence of a form of autosomal recessive spastic ataxia with early onset was originally described among French Canadians in the Charlevoix-Saguenay region, in northeastern Quebec. Since the responsible gene (SACS) was identified, mutations in the SACS gene have been described in Tunisia, Italy, Turkey, and Japan. The mutation sites found outside Quebec are different from the ones in Quebec. All patients outside Quebec, except one Italian patient, have been reported to have homozygous mutations. The authors report here identical twin sisters with novel compound heterozygous mutations (c.[2951_2952delAG]+[3922delT]) in the SACS gene.
- Published
- 2005
40. Calculation impairment in neurodegenerative diseases
- Author
-
Casey H. Halpern, Peachie Moore, Kari Dennis, Murray Grossman, and Corey T. McMillan
- Subjects
Male ,medicine.medical_specialty ,Audiology ,Neuropsychological Tests ,Alzheimer Disease ,medicine ,Memory span ,Corticobasal degeneration ,Dementia ,Humans ,Aged ,Spinocerebellar Degenerations ,Aged, 80 and over ,Psychiatric Status Rating Scales ,Working memory ,Cognitive disorder ,Subtraction ,Numerosity adaptation effect ,Neurodegenerative Diseases ,medicine.disease ,Memory, Short-Term ,Neurology ,Mental Recall ,Multivariate Analysis ,Female ,Neurology (clinical) ,Psychology ,Neuroscience ,Mathematics ,Frontotemporal dementia - Abstract
We examined oral calculation in patients with corticobasal degeneration (CBD; N=17), frontotemporal dementia (FTD; N=17), and Alzheimer’s disease (AD; N=20), as well as 17 healthy seniors matched for age and education. Our calculation model involves at least three components: numerosity, combinatorial processes, and executive resources such as working memory. We assessed addition, subtraction, multiplication, and division involving small numbers (small, single-digit answers) and large numbers (larger, single- and double-digit answers). We also assessed dot counting for small numbers (2–5) and large numbers (6–9), as well as a measure of working memory. All patient groups differed from healthy seniors in oral calculation. CBD (36% correct) and FTD (65% correct) demonstrated a significant overall impairment in oral calculation relative to AD (76% correct). CBD (66% correct) had more difficulty counting dots overall relative to AD (94% correct) and FTD (86% correct), consistent with our hypothesis that the calculation deficit in CBD is due in large part to a numerosity deficit. FTD had more difficulty relative to AD in their performance of reverse digit span, consistent with our hypothesis that FTD patients’ executive resource limitation contributes to their pattern of calculation impairment. D 2002 Elsevier Science B.V. All rights reserved.
- Published
- 2003
41. Phenotype variation correlates with CAG repeat length in SCA2--a study of 28 Japanese patients
- Author
-
Shoji Tsuji, Kunio Tashiro, Tatsuhiko Yuasa, Takeshi Ikeuchi, Takeshi Hamada, Hidenao Sasaki, Toshiyuki Fukazawa, Kazuhiro Sanpei, Kiyoshi Iwabuchi, Shuichi Igarashi, Akemi Wakisaka, and Hiroki Takano
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Ataxia ,Adolescent ,Choreiform movement ,Biology ,Japan ,Trinucleotide Repeats ,mental disorders ,medicine ,Humans ,Allele ,Age of Onset ,Genes, Dominant ,Spinocerebellar Degenerations ,Genetics ,Analysis of Variance ,Chromosomes, Human, Pair 12 ,Parkinsonism ,Genetic Variation ,Middle Aged ,medicine.disease ,nervous system diseases ,Phenotype ,Neurology ,Mutation ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,Age of onset ,medicine.symptom ,Trinucleotide repeat expansion - Abstract
Spinocerebellar ataxia-2 (SCA2) is an autosomal dominant ataxia caused by an abnormal CAG repeat expansion in a novel gene on chromosome 12q24.1. The size of the mutant allele is unstable during transmission, and correlates inversely with age at onset. We studied eight Japanese SCA2 families, including 28 patients, to assess the effect of repeat length on the phenotype features of SCA2. Frequencies of slow eye movements (SEM), reflex activity, dementia, choreiform movements, and axial tremor correlated significantly with CAG repeat size. Parkinsonism was seen in a man homozygote for SCA2 mutation. The clinical variety of SCA2 is apparently influenced by the size of the mutant allele, as is the case in other CAG repeat disorders.
- Published
- 1998
42. Clinical and molecular genetic study in seven Japanese families with spinocerebellar ataxia type 6
- Author
-
Masahiro Funauchi, Masashi Fujita, Tsuyoshi Matsubara, Tsutomu Azuma, Yoshitaka Nagai, Masao Umi, Satoshi Ueno, and Makito Hirano
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pathology ,medicine.medical_specialty ,Late onset ,Biology ,Polymerase Chain Reaction ,Degenerative disease ,Autosomal dominant cerebellar ataxia ,Trinucleotide Repeats ,medicine ,Leukocytes ,Spinocerebellar ataxia type 6 ,Humans ,Aged ,Spinocerebellar Degenerations ,Cerebellar ataxia ,DNA ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Pedigree ,Neurology ,Cerebellar atrophy ,Female ,Neurology (clinical) ,Calcium Channels ,medicine.symptom ,Age of onset ,Trinucleotide repeat expansion - Abstract
We report on seven Japanese families with spinocerebellar ataxia type 6 (SCA6) carrying small CAG repeat expansions in the calcium channel alpha1A subunit gene. The number of the expanded CAG repeat, ranged from 22 to 25, showed no intergenerational instability and had a significant inverse correlation with the age of onset. The clinical features of these patients were late onset progressive pure cerebellar ataxia with dysarthria and nystagmus, and are consistent with autosomal dominant cerebellar ataxia type III (ADCA type III). Magnetic resonance imaging scan of the brain demonstrated cerebellar atrophy with no evidence of brainstem involvement. We propose that clinical phenotype of SCA6 is compatible with ADCA type III and SCA6 is one of the most common types of ADCA in Japan.
- Published
- 1998
43. Central phenotype and related varieties of spinocerebellar ataxia 2 (SCA2): a clinical and genetic study with a pedigree in the Japanese
- Author
-
Shoji Tsuji, Toshiyuki Fukazawa, T. Koyama, Takeshi Hamada, Kunio Tashiro, Hidenao Sasaki, K. Hamada, and Akemi Wakisaka
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Ataxia ,Eye Movements ,Genetic Linkage ,Choreoathetosis ,Central nervous system disease ,Degenerative disease ,Japan ,Reflex ,medicine ,Humans ,Age of Onset ,Spinocerebellar Degenerations ,Genetics ,Neurologic Examination ,Chromosomes, Human, Pair 12 ,business.industry ,Parkinsonism ,Brain ,Syndrome ,Middle Aged ,medicine.disease ,Trinucleotide repeat disorder ,Pedigree ,Phenotype ,Neurology ,Mutation ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,Age of onset ,business ,Tomography, X-Ray Computed - Abstract
The gene for SCA2 has been mapped to chromosome 12q23-q24.1, but the mutant gene remained to be identified. When studying a Japanese family with SCA2, we noted that clinical features and disability varied among patients, with the central feature being progressive ataxia-slow eye movement-hyporeflexia syndrome. Additional symptoms were parkinsonism with minor cerebellar deficits, and severe ataxia with choreoathetosis. Our experience plus related literature documentation indicates that choreoathetosis is not so rare at the advanced stage of the disease, with onset at an early age, and that the variety of SCA2 phenotype depends on age at onset and duration of the disorder.
- Published
- 1996
44. Calbindin-D 28k immunoreactivity in the cerebellum of spinocerebellar degeneration
- Author
-
Mikio Doi, Yasuko Komatsuzaki, Tsuneo Fujita, Shin'ichi Shoji, Hidehiro Mizusawa, K. Ishikawa, Hiroyuki Iwamoto, Norio Ohkoshi, and Takesaburo Ogata
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Cerebellum ,Calbindins ,Neurofilament ,Purkinje fibers ,Purkinje cell ,Nerve Tissue Proteins ,Biology ,Calbindin ,Olivopontocerebellar atrophy ,S100 Calcium Binding Protein G ,Reference Values ,Internal medicine ,medicine ,Humans ,Aged ,Spinocerebellar Degenerations ,Aged, 80 and over ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Endocrinology ,medicine.anatomical_structure ,Neurology ,Olivopontocerebellar Atrophies ,Cerebellar atrophy ,Neurology (clinical) ,Atrophy - Abstract
We studied immunoreactivity for calbindin-D 28k (CaBP), an intracellular calcium-binding protein, in the cerebellum of control subjects and of patients with spinocerebellar degeneration (SCD) including sporadic olivopontocerebellar atrophy and familial cortical cerebellar atrophy. In the cerebellum, CaBP immunoreactivity was seen exclusively in the Purkinje cell in both SCD and control groups. However, the number of CaBP-immunoreactive Purkinje cells was significantly reduced in SCD. CaBP immunohistochemistry also disclosed abnormal morphological changes of Purkinje cells, which was not visualized on conventional stains or not clearly demonstrated on immunohistochemistry for neurofilaments. Moreover, reduced CaBP immunoreactivity was observed even in some remaining Purkinje cells of SCD suggesting that loss of CaBP precedes neuronal loss of Purkinje cell. We conclude that CaBP is a useful marker for Purkinje cell degeneration, and that reduced CaBP expression might have some association with the mechanism of the Purkinje cell degeneration in SCD.
- Published
- 1995
45. Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease
- Author
-
Pirkko Santavuori, Helena Pihko, Marjatta Lappi, A.-K. Kallio, Kimmo Sainio, and Tuula Koskinen
- Subjects
Adult ,Central Nervous System ,Male ,Pediatrics ,medicine.medical_specialty ,Ataxia ,Adolescent ,Hearing loss ,Sural nerve ,Audiology ,Medical Records ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Peripheral Nerves ,Age of Onset ,Hereditary Sensory and Autonomic Neuropathies ,Child ,Hearing Disorders ,030304 developmental biology ,Spinocerebellar Degenerations ,Athetosis ,0303 health sciences ,Epilepsy ,business.industry ,Muscles ,Infantile onset spinocerebellar ataxia ,medicine.disease ,Magnetic Resonance Imaging ,3. Good health ,Pedigree ,medicine.anatomical_structure ,Mental Health ,Neurology ,Child, Preschool ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,Age of onset ,business ,030217 neurology & neurosurgery ,Sensory nerve - Abstract
We report the clinical findings in 19 Finnish patients, including six pairs of siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive clinical symptoms manifested between one and two years of age in previously healthy infants. The first manifestation of children at that age was clumsiness and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of deep tendon reflexes were discovered on clinical examination. By school age ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy developed by adolescence. In addition, an acute crisis with status epilepticus was a late manifestation. We found a marked decrease in sensory nerve condition velocities, a progressive loss of myelinated fibers in sural nerve specimen, and abnormal background activity in EEG with advancing age. The main finding in neuroradiological investigations was cerebellar atrophy. The occurrence of the disease in siblings and lack of manifestations in parents indicate recessive inheritance.
- Published
- 1994
46. Autosomal recessive ataxia, slow eye movements, dementia and extrapyramidal disturbances
- Author
-
Jihad A. Barghouti, Mahmoud K. Al-Salem, Ali G.H. Al-Zuhair, Salah Khaffaji, Khalid Eid Al-Nassar, Ashraf Al-Kurdi, Mohammed A. Rudwan, Amir S. Najim Al-Din, Ibrahim Ayish, and Tafwiq Hamawi
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Ataxia ,Adolescent ,Eye Movements ,Degeneration (medical) ,Midbrain ,Degenerative disease ,medicine ,Dementia ,Humans ,Spinocerebellar Degenerations ,Muscle biopsy ,medicine.diagnostic_test ,Syndrome ,medicine.disease ,Slow eye movements ,Pedigree ,Peripheral neuropathy ,Neurology ,Female ,Neurology (clinical) ,medicine.symptom ,Nervous System Diseases ,Psychology ,Neuroscience - Abstract
An Arab family with an autosomal recessive form of spinocerebellar degeneration with slow eye movements is reported. Hitherto all the reported cases were either sporadic or of autosomal dominant inheritance. Associated are progressive intellectual impairment and extrapyramidal dysfunction as well as peripheral neuropathy and skeletal abnormalities. Muscle biopsy revealed non-specific mitochondrial abnormalities. The spectrum of eye movement abnormalities is discussed and the literature is reviewed. It is concluded that the hallmark of this syndrome (slow or even absent saccades) is one of a group of oculomotor abnormalities, all being characterized by delayed initiation and slow velocity. The syndrome seems to be related to the olivopontocerebellar degenerations, but differs in that there is in addition selective degeneration of certain tracts and nuclei in the mesencephalon and probably more rostral structures.
- Published
- 1990
47. Muscle pathology in Marinesco-Sjögren syndrome
- Author
-
Atsushi Komiyama, Ikuya Nonaka, and Keizo Hirayama
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Marinesco–Sjögren syndrome ,Hypergonadotropic hypogonadism ,medicine ,Humans ,Muscular dystrophy ,Myopathy ,Spinocerebellar Degenerations ,Adenosine Triphosphatases ,NADH Tetrazolium Reductase ,Muscle biopsy ,medicine.diagnostic_test ,Cerebellar ataxia ,Histocytochemistry ,business.industry ,Muscles ,medicine.disease ,Neurology ,Congenital muscular dystrophy ,Female ,Cerebellar atrophy ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Three of 4 adult patients with Marinesco-Sjögren syndrome (MSS; 2 males and 2 females, aged 26-31 years) in 2 families became non-ambulant because of slowly progressive muscular weakness rather than cerebellar ataxia. Other clinical features in these 4 patients were typical for MSS: bilateral cataracts from infancy, mental retardation, severe cerebellar atrophy, multiple skeletal abnormalities and hypergonadotropic hypogonadism. EMG demonstrated a myopathic pattern and serum CK was mildly elevated. Muscle biopsies from these 3 patients showed myopathic changes including a marked variation in fiber size, an increased number of fibers with centralized nuclei, and scattered necrotic and regenerating fibers. Fiber type analysis with myosin ATPase staining showed type 1 fiber predominance, type 2B fiber deficiency and mild increase in type 2C fibers. Muscle biopsy changes and the clinical course indicate that our MSS patients suffered from a chronic dystrophic process similar to that in congenital muscular dystrophy.
- Published
- 1989
48. Electron spin resonance studies of erythrocyte membrane in spinocerebellar degeneration
- Author
-
Hidehiko Shio, Nobuhiro Uyesaka, Yuzuru Yasuda, Ichiro Akiguchi, and Masakuni Kameyama
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,Membrane Fluidity ,Degeneration (medical) ,law.invention ,chemistry.chemical_compound ,Degenerative disease ,law ,hemic and lymphatic diseases ,Internal medicine ,Membrane fluidity ,medicine ,Humans ,Child ,Electron paramagnetic resonance ,Aged ,Spinocerebellar Degenerations ,chemistry.chemical_classification ,Erythrocyte Membrane ,Electron Spin Resonance Spectroscopy ,Fatty acid ,Middle Aged ,medicine.disease ,Red blood cell ,medicine.anatomical_structure ,Endocrinology ,Membrane ,Neurology ,chemistry ,Female ,Neurology (clinical) ,Stearic acid - Abstract
Erythrocyte membrane fluidity was examined by electron spin resonance spectra using nitroxide fatty acid spin labels in spinocerebellar degeneration (SCD). Subjects with SCD, motor neuron disease (MND) and controls did not differ in fluidity of the deep site (hydrophobic region) of the erythrocyte membrane. However, the fluidity of the shallow site (hydrophilic region) in the erythrocyte membrane was significantly less fluid in SCD than in controls and MND (outer hyperfine splitting of 5-nitroxide stearic acid: SCD 54.70 +/- 0.43 G, controls 53.57 +/- 0.41 G, MND 53.54 +/- 0.35 G, P less than 0.001). Serum HDL-cholesterol and membrane fluidity correlated significantly in controls, but not in SCD. A significant negative correlation between age and membrane fluidity was found in SCD, but not in controls. These data suggest that membrane abnormality exists in SCD and may be concerned with aging.
- Published
- 1989
49. Autosomally inherited recessive spastic ataxia, macular corneal dystrophy, congenital cataracts, myopia and vertically oval temporally tilted discs
- Author
-
Abdul Rahman Al Mahdi Mousa, Mohammed A. Rudwan, K. Behbehani, Amir S. Najim Al-Din, Khalid Eid Al-Nassar, Mohammed S.Noor Sunba, and Kassim M.J. Al-Rifai
- Subjects
Macular corneal dystrophy ,medicine.medical_specialty ,genetic structures ,business.industry ,Eye disease ,Optic disk ,Consanguinity ,Spinocerebellar Degenerations ,Audiology ,Macular degeneration ,medicine.disease ,eye diseases ,Bartter's syndrome ,Neurology ,Ophthalmology ,medicine ,Congenital cataracts ,sense organs ,Neurology (clinical) ,business - Abstract
A Bedouin family is described with an unusual form of spinocerebellar degeneration. Spastic ataxia was found to be associated with congenital cataracts, macular corneal dystrophy and non-axial myopia, in the absence of retardation of somatic or mental maturation. Immunological abnormalities were common. Genetic analysis revealed that the pedigree is expressing the transmission and segregation of a single mutant autosomal recessive gene.
- Published
- 1986
50. Multiple system atrophies
- Author
-
A.M. De Barsy, G. Van Dessel, Albert R. Lagrou, W. Dierick, and J.-J. Martin
- Subjects
Pathology ,medicine.medical_specialty ,Degeneration (medical) ,Spinocerebellar Degenerations ,Biology ,Grey matter ,medicine.disease ,Pathogenesis ,White matter ,Epilepsy ,Nursing care ,medicine.anatomical_structure ,Neurology ,medicine ,Neurology (clinical) ,Pathological - Abstract
The 5 familial cases which are reported here, showed a similar clinical course characterized by an early onset and a very long duration provided adequate nursing care was available. The main features were a very prominent pyramidal syndrome, less pronounced or partially masked cerebellar, myoclonic and extrapyramidal syndromes and preterminal sphincter disturbances which accounted for feeding difficulties, malnutrition and infections. Epilepsy was not infrequent but its management was possible with modest does of antiepileptic drugs. Investigations during life are helpful in ruling out some lipidoses such as metachromatic leucodystrophy, but they did not give any useful evidence as to pathogenesis. If one accepts an autosomal recessive inheritance (this is not completely certain), it is clear that neither clinical examination nor investigations are at present helpful in the detection of heterozygotes. The main pathological findings were multiple system atrophies and leucodystrophy. The system atrophies were qualitatively similar to those found in the classical spinocerebellar degenerations but they were much more widespread above the spinal level. The constellation of optic, thalamic, pontine, olivary, pyramidal and other long-tract lesions, among which the thalamic degeneration was unusually pronounced, appears to be unique among the abiotrophic processes. The second major pathological feature which contributes to the specificity of the syndrome, is the diffuse sclerosis of the white matter. If one attempts to classify these lesions into the conventional group of leucodystrophies, then they belong to the very large and ill-defined group of orthochromatic leucodystrophies (for a review, see Peiffer 1970b). Lipid analyses of postmortem brain tissue in 2 patients revealed a decrease in the lipid content of the white matter. No such effect was noted in grey matter. This drastic reduction - true for neutral lipids, glycolipids and phospholipids - could be interpreted as the chemical manifestation of demyelination. HFA deficiency occurring both in white and grey matter was the striking biochemical feature in our patients. This finding is rather unique and could perhaps be regarded as a primary event in this disease. A deficiency of the α-hydroxylating system is the most likely cause of this familial disorder.
- Published
- 1974
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