Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, Hunan, People's Republic of China.
Health Management Center, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Neurol Sci. 2023 Oct;44(10):3557-3566. doi: 10.1007/s10072-023-06843-4. Epub 2023 May 19.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. An increasing number of researchers have found extra motor features in ALS, which are also called ALS-plus syndromes. Besides, a great majority of ALS patients also have cognitive impairment. However, clinical surveys of the frequency and genetic background of ALS-plus syndromes are rare, especially in China.
We investigated a large cohort of 1015 patients with ALS, classifying them into six groups according to different extramotor symptoms and documenting their clinical manifestations. Meanwhile, based on their cognitive function, we divided these patients into two groups and compared demographic characteristics. Genetic screening for rare damage variants (RDVs) was also performed on 847 patients.
As a result, 16.75% of patients were identified with ALS-plus syndrome, and 49.5% of patients suffered cognitive impairment. ALS-plus group had lower ALSFRS-R scores, longer diagnostic delay time, and longer survival times, compared to ALS pure group. RDVs occurred less frequently in ALS-plus patients than in ALS-pure patients (P = 0.042) but showed no difference between ALS-cognitive impairment patients and ALS-cognitive normal patients. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus symptoms than ALS-cognitive normal group (P = 0.001).
In summary, ALS-plus patients in China are not rare and show multiple differences from ALS-pure patients in clinical and genetic features. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus syndrome than ALS-cognitive normal group. Our observations correspond with the theory that ALS involves several diseases with different mechanisms and provide clinical validation.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病。越来越多的研究人员发现 ALS 存在多种运动外特征，这些特征也被称为 ALS 伴发综合征。此外，绝大多数 ALS 患者也存在认知障碍。然而，对 ALS 伴发综合征的频率和遗传背景的临床调查很少，尤其是在中国。
我们调查了 1015 名 ALS 患者的大样本，根据不同的运动外症状将他们分为六组，并记录他们的临床表现。同时，根据他们的认知功能，我们将这些患者分为两组并比较其人口统计学特征。还对 847 名患者进行了罕见损伤变异（RDV）的基因筛查。
结果发现，16.75%的患者存在 ALS 伴发综合征，49.5%的患者存在认知障碍。与 ALS 单纯组相比，ALS 伴发组的 ALSFRS-R 评分更低，诊断延迟时间更长，生存时间更长。ALS 伴发组患者的 RDV 发生率低于 ALS 单纯组（P = 0.042），但在 ALS 认知障碍组和 ALS 认知正常组之间没有差异。此外，ALS 认知障碍组比 ALS 认知正常组更倾向于存在更多的 ALS 伴发症状（P = 0.001）。
总之，中国的 ALS 伴发患者并不罕见，在临床和遗传特征上与 ALS 单纯组有多种差异。此外，ALS 认知障碍组比 ALS 认知正常组更倾向于存在更多的 ALS 伴发综合征。我们的观察结果与 ALS 涉及不同机制的多种疾病的理论相符，为临床提供了验证。
