Di Rauso Giulia, Castellucci Andrea, Cavallieri Francesco, Tozzi Andrea, Fioravanti Valentina, Monfrini Edoardo, Gessani Annalisa, Rossi Jessica, Campanini Isabella, Merlo Andrea, Ronchi Dario, Napoli Manuela, Pascarella Rosario, Grisanti Sara, Ferrulli Giuseppe, Sabadini Rossella, Di Fonzo Alessio, Ghidini Angelo, Valzania Franco
Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Neurology, Neuroscience Head Neck Department, Azienda Ospedaliero-Universitaria di Modena, 41126 Modena, Italy.
Brain Sci. 2023 Oct 17;13(10):1467. doi: 10.3390/brainsci13101467.
(1) Background: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by late-onset cerebellar ataxia, bilateral vestibulopathy, and sensory neuronopathy mostly due to biallelic RFC1 expansion. (2) Objectives: The aim of this case series is to describe vestibular, gait, and speech alterations in CANVAS via a systematic approach. (3) Methods: All patients (n = 5) underwent a standardized clinical-instrumental examination, including the perceptual and acoustic analysis of speech, instrumental gait, and balance analysis (posturographic data were acquired using a force plate [Kistler, Winterthur, Switzerland] while 3D gait analysis, inclusive of surface electromyography, was acquired using a motion capture system [SMART DX, BTS Bioengineering, Milan, Italy], a wireless electromyograph [FreeEMG, BTS Bioengineering, Milan, Italy]), and vestibular assessment with video-oculography. (4) Results: Five patients were included in the analysis: three females (patients A, B, C) and two males (patients D and E) with a mean age at evaluation of 62 years (SD ± 15.16, range 36-74). The mean age of symptoms' onset was 55.6 years (SD ± 15.04, range 30-68), and patients were clinically and instrumentally evaluated with a mean disease duration of 6.4 years (SD ± 0.54, range 6-7). Video-Frenzel examination documented spontaneous downbeat nystagmus enhanced on bilateral gaze in all patients, except for one presenting with slight downbeat nystagmus in the supine position. All patients exhibited different degrees of symmetrically reduced VOR gain for allsix semicircular canals on the video-head impulse test and an unexpectedly normal ("false negative") VOR suppression, consistent with combined cerebellar dysfunction and bilateral vestibular loss. Posturographic indices were outside their age-matched normative ranges in all patients, while 3D gait analysis highlighted a reduction in ankle dorsiflexion (limited forward rotation of the tibia over the stance foot during the stance phase of gait and fatigue of the dorsiflexor muscles) and variable out-of-phase activity of plantar flexors during the swing phase. Finally, perceptual-acoustic evaluation of speech showed ataxic dysarthria in three patients. Dysdiadochokinesis, rhythm instability, and irregularity were observed in the oral diadochokinesis task. (5) Conclusions: CANVAS is a recently discovered syndrome that is gaining more and more relevance within late-onset ataxias. In this paper, we aimed to contribute to a detailed description of its phenotype.
(1) 背景:伴有神经病变和前庭无反射综合征的小脑共济失调(CANVAS)的特征为迟发性小脑共济失调、双侧前庭病变以及主要由双等位基因RFC1扩增引起的感觉神经元病变。(2) 目的:本病例系列的目的是通过系统方法描述CANVAS患者的前庭、步态和言语改变。(3) 方法:所有患者(n = 5)均接受了标准化的临床仪器检查,包括言语的感知和声学分析、仪器化步态分析以及平衡分析(使用测力台[瑞士温特图尔的奇石乐公司]采集姿势描记数据,同时使用运动捕捉系统[意大利米兰的BTS生物工程公司的SMART DX]和无线肌电图仪[意大利米兰的BTS生物工程公司的FreeEMG]采集包含表面肌电图的三维步态分析数据),以及通过视频眼震图进行前庭评估。(4) 结果:5名患者纳入分析:3名女性(患者A、B、C)和2名男性(患者D和E),评估时的平均年龄为62岁(标准差±15.16,范围36 - 74岁)。症状开始的平均年龄为55.6岁(标准差±15.04,范围30 - 68岁),患者接受临床和仪器评估时的平均病程为6.4年(标准差±0.54,范围6 - 7年)。视频 - 弗伦泽尔检查显示,除1例仰卧位时出现轻微下跳性眼震的患者外,所有患者在双侧凝视时均出现自发下跳性眼震增强。在视频头脉冲试验中,所有患者的6个半规管的VOR增益均呈现不同程度的对称性降低,且VOR抑制意外正常(“假阴性”),这与小脑功能障碍和双侧前庭丧失相符。所有患者的姿势描记指标均超出其年龄匹配的正常范围,而三维步态分析突出显示踝关节背屈减少(在步态站立期胫骨在支撑足上向前旋转受限以及背屈肌疲劳)以及摆动期跖屈肌的不同程度的异相活动。最后,对言语的感知 - 声学评估显示3例患者存在共济失调性构音障碍。在口腔轮替运动任务中观察到轮替运动障碍、节律不稳定和不规则。(5) 结论:CANVAS是一种最近发现的综合征,在迟发性共济失调中越来越受到关注。在本文中,我们旨在对其表型进行详细描述。