Spinocerebellar ataxia types 1, 2, 3 and 6: the clinical spectrum of ataxia and morphometric brainstem and cerebellar findings.

To assess the clinical spectrum of ataxia and cerebellar oculomotor deficits in the most common spinocerebellar ataxias (SCAs), we analysed the baseline data of the EUROSCA natural history study, a multicentric cohort study of 526 patients with either spinocerebellar ataxia type 1, 2, 3 or 6. To quantify ataxia symptoms, we used the Scale for the Assessment and Rating of Ataxia (SARA). The presence of cerebellar oculomotor signs was assessed using the Inventory of Non-Ataxia Symptoms (INAS). In a subgroup of patients, in which magnetic resonance images (MRIs) were available, we correlated MRI morphometric measures with clinical signs on an exploratory basis. The SARA subscores posture and gait (items 1-3), speech (item 4) and the limb kinetic subscore (items 5-8) did not differ between the genotypes. The scores of SARA item 3 (sitting), 5 (finger chase) and 6 (nose-finger test) differed between the subtypes whereas the scores of the remaining items were not different. In SCA1, ataxia symptoms were correlated with brainstem atrophy and in SCA3 with both brainstem and cerebellar atrophy. Cerebellar oculomotor deficits were most frequent in SCA6 followed by SCA3, whereas these abnormalities were less frequent in SCA1 and SCA2. Our data suggest that vestibulocerebellar, spinocerebellar and pontocerebellar circuits in SCA1, SCA2, SCA3 and SCA6 are functionally impaired to almost the same degree, but at different anatomical levels. The seemingly low prevalence of cerebellar oculomotor deficits in SCA1 and SCA2 is most probably related to the defective saccadic system in these disorders.

Self-rated health status in spinocerebellar ataxia--results from a European multicenter study.

Patient-based measures of subjective health status are increasingly used as outcome measures in interventional trials. We aimed to determine the variability and predictors of subjective health ratings in a possible target group for future interventions: the spinocerebellar ataxias (SCAs). A consecutive sample of 526 patients with otherwise unexplained progressive ataxia and genetic diagnoses of SCA1 (117), SCA2 (163), SCA3 (139), and SCA6 (107) were enrolled at 18 European referral centers. Subjective health status was assessed with a generic measure of health related quality of life, the EQ-5D (Euroqol) questionnaire. In addition, we performed a neurological examination and a screening questionnaire for affective disorders (patient health questionnaire). Patient-reported health status was compromised in patients of all genotypes (EQ-5D visual analogue scale (EQ-VAS) mean 61.45 +/- 20.8). Specifically, problems were reported in the dimensions of mobility (86.9% of patients), usual activities (68%), pain/discomfort (49.4%), depression/anxiety (46.4%), and self care (38.2%). Multivariate analysis revealed three independent predictors of subjective health status: ataxia severity, extent of noncerebellar involvement, and the presence of depressive syndrome. This model explained 30.5% of EQ-VAS variance in the whole sample and might be extrapolated to other SCA genotypes.

Comparison of three clinical rating scales in Friedreich ataxia (FRDA).

To test the validity and reliability of the scale for the assessment and rating of ataxia (SARA) in Friedreich ataxia (FRDA). SARA is limited to eight items and can be performed rapidly. Ninety-six patients with a molecular genetic diagnosis of FRDA were rated using three different clinical scales, the FRDA Rating Scale (FARS), the International Cooperative Ataxia Rating Scale (ICARS), and SARA. Despite considerable discrepancies in scale size and subscale structure, SARA total scores were significantly correlated with ICARS (r = 0.953, P < 0.0001) and FARS (r = 0.938, P < 0.0001) total scores. SARA total scores also correlated with the activities of daily living (ADL, r = 0.929, P < 0.0001). Although originally developed for the use in dominantly inherited ataxias, which are primarily ataxias of the cerebellar type, SARA can also be used successfully to assess afferent ataxia, which is the predominant form in FRDA. Because SARA is characterized by high interrater reliability and practicability, SARA is applicable and well suited forclinical trials of FRDA.