Achenbach Jannis, Saft Carsten, Faissner Simon, Ellrichmann Gisa
Department of Neurology, Huntington Center North Rhine-Westphalia, Ruhr-University Bochum, St. Josef-Hospital Bochum, Gudrunstraße 56, Bochum 44791, Germany.
Department of Neurology, Huntington Center North Rhine-Westphalia, Ruhr-University Bochum, St. Josef-Hospital Bochum, Bochum, Germany.
Ther Adv Neurol Disord. 2022 Jul 23;15:17562864221109750. doi: 10.1177/17562864221109750. eCollection 2022.
The role of neuroinflammation and autoimmune processes in neurodegenerative diseases is not fully understood. Activation of microglia with expression of proinflammatory cytokines supports the hypothesis that immune processes may play an important role in the pathophysiology of Huntington's disease (HD) and thus, immunomodulating therapies might have potential neuroprotective properties. Until now, no disease-modifying therapy (DMT) is available for HD.
The aim of this research was to characterize a cohort of patients suffering from both HD and autoimmune demyelinating diseases of the central nervous system (classified as G35-37 in ICD-10; ADD-CNS) in comparison to HD cases without ADD-CNS. In particular, we were interested to investigate potential modulating effects on disease manifestation and progression of HD over time of prescribed immunomodulating medications (DMT).
We analyzed the course of HD regarding motoric, functional, and cognitive aspects, using longitudinal data of up to 2 years from the worldwide registry study ENROLL-HD. Additional cross-sectional data in the largest cohort worldwide of HD patients was analyzed using demographic and molecular genetic parameters. Data were analyzed using analysis of variance (ANOVA) for cross-sectional and repeated-measures ANOVA for longitudinal parameters in IBM SPSS Statistics V.27.
Within the ENROLL-HD database, we investigated 21,116 participants and identified = 60 participants suffering from ADD-CNS. Molecular, genetic, and demographic data did not differ between groups. The subgroup of 32 participants with motor-manifest HD revealed better cognitive performance in five out of eight cognitive tests at baseline with less progression over time in two tests (all 0.05). Differentiation between DMT-treated and untreated patients revealed better cognitive and motor performance in the DMT group; those patients, however, tended to be younger. Pre-manifest HD patients simultaneously diagnosed with ADD-CNS ( 12) showed lower functional scores and more decline over time when compared with other pre-manifest HD ( 0.05).
Patients suffering from motor-manifest HD and simultaneously from ADD-CNS have better cognitive capacities compared with other motor-manifest HD patients. Moreover, DMTs might have beneficial effects on progression of neurodegeneration including the motor phenotype. However, this effect might have been biased by younger age in DMT-treated patients. Pre-manifest HD patients showed more functional impairment as expected due to their additional ADD-CNS disease.
神经炎症和自身免疫过程在神经退行性疾病中的作用尚未完全明确。小胶质细胞激活并伴有促炎细胞因子表达，这支持了免疫过程可能在亨廷顿舞蹈病（HD）病理生理学中起重要作用的假说，因此免疫调节疗法可能具有潜在的神经保护特性。到目前为止，尚无针对HD的疾病修饰疗法（DMT）。
本研究旨在对一组同时患有HD和中枢神经系统自身免疫性脱髓鞘疾病（在国际疾病分类第10版中分类为G35 - 37；ADD - CNS）的患者进行特征分析，并与无ADD - CNS的HD病例进行比较。特别是，我们感兴趣的是研究规定的免疫调节药物（DMT）对HD疾病表现和病程进展的潜在调节作用。
我们利用全球注册研究ENROLL - HD长达2年的纵向数据，分析HD在运动、功能和认知方面的病程。使用人口统计学和分子遗传学参数，对全球最大的HD患者队列中的额外横断面数据进行分析。在IBM SPSS Statistics V.27中，使用方差分析（ANOVA）进行横断面数据分析，使用重复测量方差分析进行纵向参数分析。
在ENROLL - HD数据库中，我们调查了21,116名参与者，确定了60名患有ADD - CNS的参与者。两组之间的分子、遗传和人口统计学数据没有差异。32名有运动表现的HD参与者亚组在基线时的八项认知测试中的五项中表现出更好的认知能力，并且在两项测试中随时间进展较小（所有P < 0.05）。DMT治疗组和未治疗组患者的比较显示，DMT组的认知和运动表现更好；然而，这些患者往往更年轻。与其他临床前期HD患者相比，同时被诊断为ADD - CNS的临床前期HD患者（n = 12）功能评分较低，且随时间下降更多（P < 0.05）。
与其他有运动表现的HD患者相比，同时患有ADD - CNS的有运动表现的HD患者具有更好的认知能力。此外，DMT可能对包括运动表型在内的神经退行性变进展有有益影响。然而，这种影响可能因DMT治疗组患者年龄较轻而存在偏差。正如预期的那样，临床前期HD患者由于额外患有ADD - CNS疾病，表现出更多的功能损害。
