接受 nusinersen 治疗前后成年 SMA 患者的认知表现。

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen.

机构信息

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

German Center for Neurodegenerative Diseases, Dresden, Dresden, Germany.

出版信息

BMC Neurol. 2023 Jun 6;23(1):216. doi: 10.1186/s12883-023-03261-z.

DOI:10.1186/s12883-023-03261-z

PMID:37280513

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10243018/

Abstract

BACKGROUND

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease caused by mutations of the SMN1 gene. Deficient SMN protein causes irreversible degeneration of alpha motor neurons characterized by progressive muscle weakness and atrophy. Considering that SMA is a multi-systemic disorder and SMN protein was found to be expressed in cortical structures, the cognitive profile of adult patients with SMA has recently been of particular interest. With nusinersen, a novel, disease-modifying drug has been established, but its effects on neuropsychological functions have not been validated yet. Aim of this study was to investigate the cognitive profile of adult patients with SMA during treatment initiation with nusinersen and to reveal improvement or deterioration in cognitive performance.

METHODS

This monocentric longitudinal study included 23 patients with SMA type 2 and 3. All patients were assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) before and after 14 months of treatment initiation with nusinersen. Additionally, motor function was evaluated by Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R).

RESULTS

Of the treatment-naive patients, only three were below the age- and education-matched cut-off for cognitive impairment in the ECAS total score. Significant differences between SMA type 2 and 3 were only detected in the domain of Language. After 14 months of treatment, patients showed significant improvement of absolute scores in all three ALS-specific domains, in the non-ALS-specific domain of Memory, in both subscores and in the ECAS total score. No associations were detected between cognitive and functional outcome measures.

CONCLUSIONS

In some adult patients with SMA abnormal cognitive performance in ALS-specific functions of the ECAS was evident. However, the presented results suggest no clinically significant cognitive changes during the observed treatment period with nusinersen.

摘要

背景

脊髓性肌萎缩症（SMA）是一种由 SMN1 基因突变引起的遗传性神经肌肉疾病。SMN 蛋白缺失导致α运动神经元进行性变性，表现为进行性肌无力和萎缩。鉴于 SMA 是一种多系统疾病，且 SMN 蛋白在皮质结构中表达，最近成人 SMA 患者的认知特征引起了特别关注。随着新型疾病修饰药物nusinersen 的出现，但其对神经心理学功能的影响尚未得到验证。本研究旨在探讨 nusinersen 治疗起始时成人 SMA 患者的认知特征，并揭示认知表现的改善或恶化。

方法

这是一项单中心纵向研究，纳入了 23 例 SMA 2 型和 3 型患者。所有患者在接受 nusinersen 治疗 14 个月前后均使用爱丁堡认知和行为 ALS 筛查（ECAS）进行评估。此外，运动功能通过改良 Hammersmith 功能运动量表（HFMSE）、修订版上肢模块（RULM）和肌萎缩侧索硬化功能评定量表修订版（ALSFRS-R）进行评估。

结果

在未经治疗的患者中，仅有 3 名患者的 ECAS 总分认知障碍年龄和教育匹配切点以下。SMA 2 型和 3 型之间仅在语言域中存在显著差异。治疗 14 个月后，患者在所有三个 ALS 特异性域、非 ALS 特异性域的记忆、两个亚量表和 ECAS 总分的绝对评分上均有显著改善。未检测到认知和功能结局指标之间的相关性。