Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia

被引：55

作者：

Giordano, Ilaria ^{[1
,2
]}

Harmuth, Florian ^{[3
]}

Jacobi, Heike ^{[2
,5
]}

Paap, Brigitte ^{[2
]}

Vielhaber, Stefan ^{[6
,7
]}

Machts, Judith ^{[7
]}

Schoels, Ludger ^{[4
,8
]}

Synofzik, Matthis ^{[3
,4
,8
]}

Sturm, Marc

Tallaksen, Chantal ^{[9
,10
]}

Wedding, Iselin M. ^{[9
]}

Boesch, Sylvia ^{[11
]}

Eigentler, Andreas ^{[11
]}

van de Warrenburg, Bart ^{[12
]}

van Gaalen, Judith ^{[12
]}

Kamm, Christoph ^{[13
,14
]}

Dudesek, Ales ^{[13
,14
]}

Kang, Jun-Suk ^{[15
]}

Timmann, Dagmar ^{[16
]}

Silvestri, Gabriella ^{[17
]}

Masciullo, Marcella ^{[18
]}

Klopstock, Thomas ^{[1
,19
,20
]}

Neuhofer, Christiane ^{[19
,20
]}

Ganos, Christos ^{[22
]}

Filla, Alessandro ^{[23
]}

Bauer, Peter ^{[24
]}

du Montcel, Sophie Tezenas ^{[25
,26
]}

Klockgether, Thomas ^{[2
,21
]}

机构：

[1] Univ Hosp Bonn, Dept Neurol, Bonn, Germany

[2] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[3] Univ Tubingen, Hertie Inst Clin Brain Res, Inst Med Genet & Appl Genom, Tubingen, Germany

[4] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany

[5] Heidelberg Univ Hosp, Dept Neurol, Heidelberg, Germany

[6] Otto von Guericke Univ, Dept Neurol, Magdeburg, Germany

[7] German Ctr Neurodegenerat Dis DZNE, Magdeburg, Germany

[8] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany

[9] Oslo Univ Hosp, Dept Neurol, Oslo, Norway

[10] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway

[11] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[12] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Nijmegen, Netherlands

[13] Univ Rostock, Dept Neurol, Rostock, Germany

[14] German Ctr Neurodegenerat Dis DZNE, Rostock, Germany

[15] Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany

[16] Univ Duisburg Essen, Essen Univ Hosp, Dept Neurol, Duisburg, Germany

[17] Univ Cattolica Sacro Cuore, Inst Neurol, Milan, Italy

[18] IRCCS, Fdn Santa Lucia, SPInal Rehabil Lab SPIRE, Rome, Italy

[19] Ludwig Maximilians Univ Munchen, Friedrich Baur Inst, Dept Neurol, Munich, Germany

[20] German Ctr Neurodegenerat Dis DZNE, Munich, Germany

[21] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[22] Univ Med Ctr Hamburg Eppendorf UKE, Dept Neurol, Hamburg, Germany

[23] Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy

[24] Centogene AG, Rostock, Germany

[25] Pierre & Marie Curie Univ UPMC, Pierre Louis Inst Epidemiol & Publ Hlth, Paris, France

[26] Grp Hosp Pitie Salpetriere, AP HP, Biostat Unit, Paris, France

来源：

NEUROLOGY | 2017年 / 89卷 / 10期

关键词：

MULTIPLE SYSTEM ATROPHY; CEREBELLAR-ATAXIA; HEREDITARY ATAXIAS; NATURAL-HISTORY; VALIDATION; DIAGNOSIS; PARAPLEGIAS; ETIOLOGY; SCALE;

D O I：

10.1212/WNL.0000000000004311

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations. Methods: The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing. Results: The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94+/-0.74, p<0.0001) and disease duration (0.22+/-0.06 per additional year, p=0.0007) were associated with a higher SARA score. Forty-eight participants who did not fulfill MSA-C criteria and had a disease duration of >10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6+/-6.0 vs 16.0+/-5.8, p=0.0200) and a slower annual SARA increase (1.1+/-2.3 vs 3.3+/-3.2, p=0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made. Conclusions: Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort.

引用

页码：1043 / 1049

页数：7

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