Composite autonomic severity scoring in spinocerebellar ataxia type 1 and 2.

OBJECTIVES: The aim of the present study was to evaluate the integrity of autonomic nervous system in spinocerebellar ataxia (SCA) type 1 and 2 patients using battery of autonomic function tests and their comprehensive scoring using composite autonomic severity score (CASS). MATERIAL AND METHODS: Battery of autonomic function test comprising of cardiovascular (baroreflex dependent and non-baroreflex dependent) and sudomotor functions were assessed in age and gender-matched SCA1 (n = 31), SCA2 (n = 40) patients along with healthy controls (n = 40). To assess the grade of autonomic abnormalities, the composite autonomic severity score (CASS) was computed using the results of the standard autonomic function tests. RESULTS: We found reduction in baroreflex dependent autonomic reactivity parameters predominantly a significant fall of systolic blood pressure (<0.001) and lower 30:15 ratio (<0.001) during head up tilt in both the SCA1 and SCA2 as compared to controls. On sudomotor assessment, distal leg latency of sweat response was prolonged in SCA1 than SCA2 patients. Moderate generalized autonomic failure was commonly found amongst SCA1 (80.65%) and SCA2 (85%) patients. Severe autonomic failure was found to be more in SCA1 (6.45%) than SCA2 (2.50%) patients. CONCLUSIONS: Cardiovascular autonomic function assessment in SCA1 and SCA2 patients revealed a significant impairment in the baroreflex loop integrity. Severity scoring using CASS suggests the existence of moderate autonomic failure in majority of both SCA1 and SCA2 patients.

Cortical and Subcortical Brain Area Atrophy in SCA1 and SCA2 Patients in India: The Structural MRI Underpinnings and Correlative Insight Among the Atrophy and Disease Attributes.

INTRODUCTION: Genetically defined spinocerebellar ataxia (SCA) type 1 and 2 patients have differential clinical profile along with probable distinctive cortical and subcortical neurodegeneration. We compared the degree of brain atrophy in the two subtypes with their phenotypic and genotypic parameters. METHODS: MRI was performed using a 3T scanner (Philips, Achieva) to obtain 3D T1-weighted scans of the whole brain and analyzed by FreeSurfer (version 5.3 and 6 dev.) software. Genetically proven SCA1 (n = 18) and SCA2 (n = 25) patients with age-matched healthy controls (n = 8) were recruited. Clinical severity was assessed by the International Cooperative Ataxia Rating Scale (ICARS). To know the differential pattern of atrophy, the groups were compared using ANOVA/Kruskal-Wallis test and followed by correlation analysis with multiple corrections. Further, machine learning-based classification of SCA subtypes was carried out. RESULT: We found (i) bilateral frontal, parietal, temporal, and occipital atrophy in SCA1 and SCA2 patients; (ii) reduced volume of cerebellum, regions of brain stem, basal ganglia along with the certain subcortical areas such as hippocampus, amygdala, thalamus, diencephalon, and corpus callosum in SCA1 and SCA2 subtypes; (iii) higher subcortical atrophy SCA2 than SCA1 (iv) correlation between brain atrophy and disease attributes; (v) differential predictive pattern of two SCA subtypes using machine learning approach. CONCLUSION: The present study suggests that SCA1 and SCA2 do not differ in cortical thinning while a characteristic pattern of subcortical atrophy SCA2 > SCA1 is observed along with correlation of brain atrophy and disease attributes. This may provide the diagnostic guidance of MRI to SCA subtypes and differential therapies.

Structural atrophy of central autonomic network correlates with the functional attributes of autonomic nervous system in spinocerebellar ataxia patients.

OBJECTIVE: Spinocerebellar ataxia (SCA) is a neurodegenerative disorder in which, autonomic dysfunction is a common manifestation. Brain area atrophy also involves the areas comprising central autonomic network (CAN) in SCA. Structural atrophy of CAN and autonomic dysfunction should go hand in hand. But this important relationship has not been studied to date. Therefore, using SCA as a disease model, the present study has been designed to explore the plausible correlations between the brain areas of CAN and clinical autonomic function modalities in SCA patients. MATERIALS AND METHODS: 3D T1-weighted scans were acquired on 3T MRI, analyzed by FreeSurfer software in genetically confirmed forty-nine SCA patients (SCA1 = 18, SCA2 = 25 and SCA3 = 6). Heart rate variability (HRV), blood pressure variability (BPV), baroreflex sensitivity (BRS), and autonomic reactivity tests were used for evaluation of autonomic nervous system. Additionally, autonomic dysfunction scoring was done using composite autonomic severity score (CASS). RESULTS: On correlation analysis, the study showed the association of atrophic cortical and subcortical brain areas (predominantly prefrontal cortex, bilateral middle temporal, left cuneus, left lingual and left caudate) with altered clinical autonomic function parameters in SCA patients. These areas were primarily comprised of sympathetic and parasympathetic brain areas of CAN. One of the key brain areas of CAN - left cuneus was found to be associated with both HRV (r = 0.295, p = 0.040) and BRS (r = 0.326, p = 0.022). CONCLUSION: A characteristic pattern of association between particular brain areas of CAN and clinical autonomic function parameters was observed in SCA patients.

Depressed baroreflex sensitivity from spontaneous oscillations of heart rate and blood pressure in SCA1 and SCA2.

OBJECTIVES: To assess the time and frequency domain measures of cardiac autonomic activity/tone in patients of genetically defined spinocerebellar ataxia (SCA) types 1 and 2, as well as to decipher the probable associations among the cardiovascular autonomic parameters and genetic and clinical characteristics. MATERIALS AND METHODS: Simultaneous 5-min recording of RR interval (RRI) and blood pressure (BP) for the calculation of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were performed in genotypically confirmed SCA1 (n = 31) and SCA2 (n = 40) patients and healthy controls (n = 40). Additionally, the International Cooperative Ataxia Rating Scale (ICARS) was used for scoring of clinical severity in SCA patients. RESULTS: Time and frequency domain parameters of HRV, BPV and BRS were depressed in SCA1 and SCA2 subtypes as compared to controls, although there was no statistically significant difference in autonomic tone between the two SCA subtypes. On correlation analysis, autonomic tone parameters were found to be associated with the clinical and genetic features of the SCA subtypes. Also, ICARS was associated with the genotype (CAG repeat length) in SCA2 patents. CONCLUSIONS: Cardiac autonomic tone is depressed in both SCA1 and 2 as compared to healthy controls while the two SCA subtypes do not differ in terms of autonomic tone. Also, a typical association exists between disease characteristics and autonomic indices.