Spinocerebellar ataxias type 1, 2 and 3: a study of heart rate variability Introduction Autosomal-dominant spinocerebellar ataxias (SCA) are a family of disorders characterized by inherited gene mutation. They are classified based on genotyping into distinct subgroups, the more common being SCA1, SCA2 and SCA3 (Mach- ado–Joseph disease). These disorders are charac- terized clinically by ataxia, dysarthria and brainstem dysfunction with varying degrees of ophthalmoparesis occurring in the third or fourth decade, although childhood onset is also known (1–3). Heart rate variability (HRV) is a function of the cardiac efferents to the sinus node and is composed of parasympathetic and sympathetic components. These include both central and peripheral auto- nomic regulation. Beat-to-beat variability is a function of the parasympathetic modulation (4, 5), while long-term variation through reflexes including baro-receptors is secondary to sympa- thetic modulation (4, 5). Clinical autonomic com- plaints are reported in SCA1, SCA2 and SCA3 (6–10) and may be central or peripheral (7–12). Heart rate variability analysis is a sensitive method to detect subclinical cardiac autonomic dysfunction (4, 5). Standard deviation of RR interval (RR_SD) is a measure of the overall variability and is decreased in autonomic dysfunc- tion (4, 5, 8). Parasympathetic dysfunction is also characterized by a reduction in the absolute power of high frequency spectrum with a relative reduc- tion of high frequency power in normalized units and a normal or raised low frequency to high frequency ratio. Low frequency power is a marker of sympathetic activity or combined sympathetic and parasympathetic activity (4, 5, 13). We studied the prevalence and nature of cardiac autonomic dysfunction using an analysis of HRV parameters in patients with genotypically proven SCA. We also studied the correlations between the CAG repeat length and HRV dysfunction in SCA1. Materials and methods This study was conducted at the National Institute of Mental Health & Neurosciences, a university teaching hospital in South India. The protocol was Acta Neurol Scand 2008: 117: 337–342 DOI: 10.1111/j.1600-0404.2007.00945.x Copyright Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA Pradhan C, Yashavantha BS, Pal PK, Sathyaprabha TN. Spinocerebellar ataxias type 1, 2 and 3: a study of heart rate variability. Acta Neurol Scand 2008: 117: 337–342. Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard. Objective – To detect cardiac autonomic dysfunction, using analysis of heart rate variability in genetically defined spinocerebellar ataxias (SCA). Materials and methods – Consecutive RR intervals were analyzed for time- and frequency- domain parameters in 22 genotypically proven SCA patients (SCA1 = 11, SCA2 = 6 and SCA3 = 5) and compared with that of age- and gender- matched controls. Results – Reduction in the standard deviation of RR interval (RR_SD) was seen in 72.7% of SCA patients. There was a reduction in both the parasympathetic and sympathetic parameters in SCA without any change in the ratio of low- to high- frequency power. In SCA1, there was a significant negative correlation between RR_SD and duration of illness but not with the CAG repeat lengths of the abnormal allele. Small sample size of SCA2 and SCA3 precluded similar comparison. Conclusions – Cardiac autonomic dysfunction, predominantly parasympathetic, was seen in SCA, and the severity correlated with the duration of illness in SCA1. C. Pradhan 1 , B. S. Yashavantha 1 , P. K. Pal 1 , T. N. Sathyaprabha 2 Departments of 1 Neurology and 2 Neurophysiology, National Institute of Mental Health & Neurosciences, Bangalore, India Key words: spinocerebellar ataxias; spectrum analysis; trinucleotide repeats Dr. Pramod Kr. Pal, Associate Professor, Department of Neurology, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore-560029, India Tel.: +91 80 26995147, +91 80 26995150 Fax: +91 80 26579299 e-mail: pkpal_2007@rediffmail.com Accepted for publication September 11, 2007 337