Chipika Rangariroyashe H, Mulkerrin Grainne, Pradat Pierre-François, Murad Aizuri, Ango Fabrice, Raoul Cédric, Bede Peter
Computational Neuroimaging Group, Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Pitié-Salpêtrière University Hospital, Sorbonne University, Paris, France.
Neural Regen Res. 2022 Nov;17(11):2335-2341. doi: 10.4103/1673-5374.336139.
Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition. The clinical picture is dominated by upper and lower motor neuron degeneration, but extra-motor pathology is increasingly recognized, including cerebellar pathology. Post-mortem and neuroimaging studies primarily focus on the characterization of supratentorial disease, despite emerging evidence of cerebellar degeneration in amyotrophic lateral sclerosis. Cardinal clinical features of amyotrophic lateral sclerosis, such as dysarthria, dysphagia, cognitive and behavioral deficits, saccade abnormalities, gait impairment, respiratory weakness and pseudobulbar affect are likely to be exacerbated by co-existing cerebellar pathology. This review summarizes in vivo and post mortem evidence for cerebellar degeneration in amyotrophic lateral sclerosis. Structural imaging studies consistently capture cerebellar grey matter volume reductions, diffusivity studies readily detect both intra-cerebellar and cerebellar peduncle white matter alterations and functional imaging studies commonly report increased functional connectivity with supratentorial regions. Increased functional connectivity is commonly interpreted as evidence of neuroplasticity representing compensatory processes despite the lack of post-mortem validation. There is a scarcity of post-mortem studies focusing on cerebellar alterations, but these detect pTDP-43 in cerebellar nuclei. Cerebellar pathology is an overlooked facet of neurodegeneration in amyotrophic lateral sclerosis despite its contribution to a multitude of clinical symptoms, widespread connectivity to spinal and supratentorial regions and putative role in compensating for the degeneration of primary motor regions.
肌萎缩侧索硬化症是一种无情进展的多系统疾病。临床表现以上下运动神经元变性为主，但运动外病理改变越来越受到认可，包括小脑病理改变。尽管有证据表明肌萎缩侧索硬化症存在小脑变性，但尸检和神经影像学研究主要集中在幕上疾病的特征描述上。肌萎缩侧索硬化症的主要临床特征，如构音障碍、吞咽困难、认知和行为缺陷、扫视异常、步态障碍、呼吸肌无力和假性球麻痹，可能会因并存的小脑病理改变而加重。本综述总结了肌萎缩侧索硬化症小脑变性的体内和尸检证据。结构成像研究一致发现小脑灰质体积减少，扩散研究很容易检测到小脑内和小脑脚白质改变，功能成像研究通常报告与幕上区域的功能连接增加。尽管缺乏尸检验证，但功能连接增加通常被解释为代表代偿过程的神经可塑性证据。专注于小脑改变的尸检研究很少，但这些研究在小脑核中检测到pTDP-43。小脑病理改变是肌萎缩侧索硬化症神经变性中一个被忽视的方面，尽管它导致了多种临床症状，与脊髓和幕上区域广泛连接，并在补偿初级运动区域的变性中可能发挥作用。
