Pulido-Valdeolivas Irene, Gómez-Andrés David, Sanz-Gallego Irene, Rausell Estrella, Arpa Javier
Department of Anatomy, Histology and Neuroscience, School of Medicine, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo 4, 28029 Madrid, Spain ; Trastornos del Desarrollo y Maduración Neurológica (TRADESMA), IdiPaz-UAM, Madrid, Spain ; Department of Neurology, Hospital Universitario La Paz, Madrid, Spain.
Department of Anatomy, Histology and Neuroscience, School of Medicine, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo 4, 28029 Madrid, Spain ; Trastornos del Desarrollo y Maduración Neurológica (TRADESMA), IdiPaz-UAM, Madrid, Spain ; Department of Pediatrics, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain.
Cerebellum Ataxias. 2016 Feb 23;3:4. doi: 10.1186/s40673-016-0042-6. eCollection 2016.
Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder that affects the cerebellar system and other subcortical regions of the brain. As for other cerebellar diseases, the severity of this type of ataxia can be assessed with the Scale for Assessment and Rating of Ataxia (SARA) which gives a total score that reflects functional impairment out of 8 cerebellar function tests. SCA3 patients score profile is heterogeneous on at the start of follow up. This study investigates possible patterns in those profiles and analyses the impact of other usually concurrent signs of impairment of extracerebellar motor systems in that profile variability by means of multivariate statistical approaches.
Seventeen patients with SCA3 underwent systematic anamnesis, neurological and SARA assessment, visual evaluation of (123)I-Ioflupane (DaTSCAN) single-photon emission computed tomography (SPECT) imaging and electrophysiological studies (nerve conduction and electromyography). Patterns in the profiles of SARA item scores were investigated by hierarchical clustering after multivariate correspondence analysis. A network analysis was used to represent relationships between SARA item scores, clinical, genetic and neurological examination parameters as well as abnormalities of DaTSCAN SPECT imaging and electrophysiological studies.
The most frequently altered SARA items in all patients are gait and stance, and three profiles of SCA3 patients can be distinguished depending mainly on their degree of impairment in those two items. Other SARA items like the score on heel-shin slide contribute less to the classification. Network analysis shows that SARA item scores configure a single domain that is independent of the size of the mutated expanded allele and age of onset, which are, in turn closely and inversely correlated. The severity of cerebellar dysfunction is correlated with longer disease duration, altered visual evaluation of DaTSCAN SPECT imaging and decreased patellar reflexes. Neither the presence of pyramidal or extrapyramidal signs nor the intensity of polyneuropathy is correlated with the SARA items scores.
Pattern recognition approaches are useful tools to describe clinical phenotypes of ataxias and to identify particular configurations of cerebellar signs.
3型脊髓小脑共济失调（SCA3）是一种神经退行性疾病，会影响小脑系统及大脑的其他皮质下区域。与其他小脑疾病一样，这种共济失调的严重程度可用共济失调评估与分级量表（SARA）进行评估，该量表通过8项小脑功能测试得出一个反映功能损害的总分。在随访开始时，SCA3患者的评分情况具有异质性。本研究调查了这些评分情况中可能存在的模式，并通过多变量统计方法分析了小脑外运动系统其他常见并发损伤体征对该评分变异性的影响。
17例SCA3患者接受了系统的问诊、神经学和SARA评估、（123）I-碘氟烷（DaTSCAN）单光子发射计算机断层扫描（SPECT）成像的视觉评估以及电生理研究（神经传导和肌电图）。在多变量对应分析后，通过层次聚类研究SARA项目评分情况中的模式。使用网络分析来表示SARA项目评分、临床、遗传和神经学检查参数以及DaTSCAN SPECT成像和电生理研究异常之间的关系。
所有患者中最常改变的SARA项目是步态和姿势，根据这两个项目的损害程度，可区分出三种SCA3患者的评分情况。其他SARA项目，如跟膝胫试验评分，对分类的贡献较小。网络分析表明，SARA项目评分构成一个独立于突变扩展等位基因大小和发病年龄的单一域，而突变扩展等位基因大小和发病年龄又密切负相关。小脑功能障碍的严重程度与病程延长、DaTSCAN SPECT成像视觉评估改变和髌反射减弱相关。锥体束或锥体外系体征的存在以及多神经病的严重程度均与SARA项目评分无关。
模式识别方法是描述共济失调临床表型和识别小脑体征特定组合的有用工具。
