Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study
Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study
复制标题
DOI：
10.1007/s00415-022-11253-1
复制
发表时间：
2022-07-23
影响因子：
6
通讯作者：
Anheim, M.
中科院分区：
文献类型：
--
作者：
Bogdan, T.;Wirth, T.;Anheim, M.
背景：尽管遗传学领域最近取得了进展，但散发性迟发性(>；40年)小脑性共济失调(SLOCA)的病因仍然经常难以捉摸，而最佳的诊断方案仍然需要确定。我们的目的是全面描述SLOCA的原因，并讨论调查的相关性。方法我们纳入了我们转诊中心连续收治的205例SLOCA患者。采用详尽的临床评估、生化、遗传学、电生理和影像检查对患者进行前瞻性调查。结果确诊135例(66%)，报告了26种不同的病因，最常见的是多系统萎缩小脑型(MSA-C)(41%)。51名患者(25%)有各种原因引起的SLOCA，包括免疫介导性疾病，如多发性硬化症或抗GAD抗体介导性共济失调；以及其他原因，如酒精性小脑变性，浅表铁质沉着症，或克雅病。我们还在20名患者中确定了11种遗传原因，包括SPG7(n=4)，RFC1相关Canvas(n=3)，SLC20A2(n=3)，极晚发型Friedreich‘s共济失调(n=2)，FXTAS(n=2)，SCA3(n=1)，SCA17(n=1)，DRPLA(n=1)，MYORG(n=1)，MELAS(n=1)，和线粒体病(n=1)没有MSA-C(p<；0.001)严重。其余患者(34%)有特发性迟发性小脑性共济失调，其严重程度低于MSA-C(p<；0.01)。结论我们的前瞻性研究对SLOCA的病因提供了详尽的描述，并提供了有关调查和诊断检查结果的线索。基于我们的观察，我们建立了一种SLOCA的诊断算法。
Background Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. Methods We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. Results We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). Conclusion Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.