Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B)

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2024-09-12 DOI:10.1002/ana.27060

Widad Abou Chaar MD, Anirudh N. Eranki, Hannah A. Stevens, Sonya L. Watson MS, Darice Y. Wong PhD, Veronica S. Avila, Megan Delfeld, Alexander J. Gary, Sanjukta Tawde MS, Malia Triebold MS, Marcello Cherchi MD, PhD, Tao Xie MD, PhD, Paul J. Lockhart PhD, Melanie Bahlo PhD, David Pellerin MD, MSc, Marie-Josée Dicaire, Matt Danzi PhD, Stephan Zuchner MD, PhD, Bernard C. Brais MD, PhD, Susan Perlman MD, Margit Burmeister PhD, Henry Paulson MD, PhD, Sharan Srinivasan MD, PhD, Lawrence Schut MD, Matthew Bower MS, Khalaf Bushara MD, Chuanhong Liao MS, Vikram G. Shakkottai MD, PhD, John Collins MD, PhD, H. Brent Clark MD, PhD, Soma Das PhD, Brent L. Fogel MD, PhD, Christopher M. Gomez MD, PhD

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引用次数: 0

Abstract

Objectives

Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.

Methods

We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B.

Results

In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine.

Interpretation

Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024;96:1092–1103

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美国脊髓小脑共济失调（SCA27B）大样本的临床、放射学和病理学特征

摘要：由于成纤维细胞生长因子 14（FGF14）基因中的 GAA 重复扩增导致的小脑共济失调 27B 最近被认为是晚发性遗传性小脑共济失调的常见病因。在此，我们首次在美国人群中报告了这种疾病，并对102例GAA重复扩增患者的临床表现、疾病进展、病理异常以及对4-氨基吡啶的反应进行了描述。临床表现和患者人口统计学资料是使用标准化表格从临床记录中以非盲法回顾性收集的。结果在我们的 102 名 SCA27B 患者队列中，我们发现 SCA27B 是一种晚发（57 ± 12.5 岁）缓慢进行性共济失调，51% 的患者有发作性共济失调。起病时几乎总是存在平衡和步态障碍。对 4 个大脑标本进行尸检的主要发现是 Purkinje 神经元的缺失，这种缺失在蚓部最为严重，尤其是在前蚓部。我们的研究进一步估计了SCA27B的患病率，并进一步扩展了SCA27B的临床、影像和病理特征，同时研究了该病患者的治疗反应、疾病进展和生存情况。所有未确诊的共济失调患者，尤其是偶发性发病的患者，都应考虑进行SCA27B检测。ann neurol 2024

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.