Spinocerebellar Ataxia Types 1, 2, 3 and 6: the Clinical Spectrum of Ataxia and Morphometric Brainstem and Cerebellar Findings

Abstract

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.

Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

“…These findings were observed in only one out of 42 German patients 10 . This observation is in line with the viewpoint shared by Jacobi et al among other groups, who state that there is a significant overlapping among different SCA, impeding purely clinical based diagnoses 11 . Stevanin, Dürr and Brice 12 suggested that BE is not common among non-Portuguese Western European SCA3 patients, and might, therefore, be related to ethnic background.…”

Clinical Evaluation of Eye Movements in Spinocerebellar Ataxias

“…GEN is almost universal in SCA 6 (7,20–22). The infrequency of GEN in SCA 2 has been noted in other clinical studies (11,12). Eye movement recordings have either not detected GEN in SCA 2 (10) or found it in fewer than 50% of subjects (7,20).…”

“…SCAs are associated with a variety of abnormalities in eye movements; some of these results from abnormalities in cerebellar control, whereas others reflect extracerebellar pathology. Previous publications have documented the type of abnormalities noted in families examined during gene identification studies, in small scale reports using eye movement recordings (4–10) and in larger patient cohorts of SCA subjects (11,12). We summarize the findings of bedside ocular motor examination performed prospectively in a large cohort of patients with SCAs 1, 2, 3, and 6 and examine factors that may influence their presence.…”

Progression of Microstructural Damage in Spinocerebellar Ataxia Type 2: A Longitudinal DTI Study

“…1 Gliosis has been observed also in the thalamus, globus pallidus, and subthalamic region. 1 MR imaging shows loss of bulk of the brain stem and cerebellum in presymptomatic and early symptomatic SCA2 gene carriers [4][5][6] and circumscribed atrophy of the frontal, parietal, and temporal cortex, the thalamus, and frontal and temporal WM in more advanced cases. 19,45,46 MR imaging can also show diffuse high signal intensity of the brain stem and cerebellar WM with sparing of the corticospinal tracts in proton-attenuation and T2-weighted images.…”

“…1,3 MR T1-weighted imaging enables in vivo detection of brain stem and cerebellar atrophy in patients with SCA2 in crosssectional [4][5][6] and longitudinal 7 studies. Recently, DWI and DTI have enabled quantitative assessment of the microstructural changes in brain tissue that result from neurodegenerative diseases.…”