Department of Pediatrics, University of Groningen, Groningen, the Netherlands.
Department of Neurology and University of Groningen, Groningen, the Netherlands.
Eur J Paediatr Neurol. 2022 Jan;36:123-129. doi: 10.1016/j.ejpn.2021.12.001. Epub 2021 Dec 7.
The high prevalence of mixed phenotypes of Early Onset Ataxia (EOA) with comorbid dystonia has shifted the pathogenetic concept from the cerebellum towards the interconnected cerebellar motor network. This paper on EOA with comorbid dystonia (EOA-dystonia) explores the conceptual relationship between the motor phenotype and the cortico-basal-ganglia-ponto-cerebellar network.
In EOA-dystonia, we reviewed anatomic-, genetic- and biochemical-studies on the comorbidity between ataxia and dystonia.
In a clinical EOA cohort, the prevalence of dystonia was over 60%. Both human and animal studies converge on the underlying role for the cortico-basal-ganglia-ponto-cerebellar network. Genetic -clinical and -in silico network studies reveal underlying biological pathways for energy production and neural signal transduction.
EOA-dystonia phenotypes are attributable to the cortico-basal-ganglia-ponto-cerebellar network, instead of to the cerebellum, alone. The underlying anatomic and pathogenetic pathways have clinical implications for our understanding of the heterogeneous phenotype, neuro-metabolic and genetic testing and potentially also for new treatment strategies, including neuro-modulation.
早发性共济失调（EOA）伴发共病性肌张力障碍的混合表型高发，已将致病概念从小脑转移到相互连接的小脑运动网络。本文探讨了伴发肌张力障碍的 EOA（EOA-肌张力障碍）的运动表型与皮质基底节桥脑小脑网络之间的概念关系。
在 EOA-肌张力障碍中，我们回顾了关于共济失调和肌张力障碍共病的解剖学、遗传学和生化研究。
在临床 EOA 队列中，肌张力障碍的患病率超过 60%。人类和动物研究都集中在皮质基底节桥脑小脑网络的潜在作用上。遗传-临床和-计算机网络研究揭示了能量产生和神经信号转导的潜在生物学途径。
EOA-肌张力障碍表型归因于皮质基底节桥脑小脑网络，而不仅仅是小脑。潜在的解剖和发病途径对我们理解异质性表型、神经代谢和遗传检测具有临床意义，并可能为新的治疗策略提供依据，包括神经调节。
