Sudomotor dysfunction is frequent and correlates with disability in Friedreich ataxia Karen A.G. Takazaki a , Thiago Junqueira R. Rezende a , Alberto R.M. Martinez a , Carelis Gonzalez-Salazar a , Anamarli Nucci a , Iscia Lopes-Cendes b , Marcondes C. França Jr. a,⇑ a Departments of Neurology, School of Medical Sciences, University of Campinas – UNICAMP, Campinas, SP, Brazil b Medical Genetics, School of Medical Sciences, University of Campinas – UNICAMP, Campinas, SP, Brazil article info Article history: Accepted 22 August 2018 Available online 31 August 2018 Keywords: Friedreich’s ataxia Autonomic nervous system Heart rate variability Sudomotor function QSART highlights  Cardiovascular dysautonomia is not common in Friedreich’s ataxia (FRDA).  Sudomotor dysfunction is frequent and related to peripheral damage in FRDA.  QSART correlates with ataxia severity and is a promising biomarker for FRDA. abstract Objectives: To evaluate autonomic symptoms and function in Friedreich’s Ataxia (FRDA). Methods: Twenty-eight FRDA patients and 24 controls underwent clinical/electrophysiological testing. We employed the Friedreich’s Ataxia Rating Scale (FARS) and the Scales for Outcomes in Parkinson’s Disease: Autonomic Questionnaire-SCOPA-AUT to estimate the intensity of ataxia and autonomic com- plaints, respectively. Cardiovagal tests and the quantitative sudomotor axonal reflex, Q-SART, were then assessed in both groups. Results: In the patient group, there were 11 men with mean age of 31.5 ± 11.1 years. Mean SCOPA-AUT score was 15.1 ± 8.1. Minimum RR interval at rest was shorter in the FRDA group (Median 831.3  724.0 ms, p < 0.001). The 30:15 ratio, Valsalva index, E:I ratio, low and high frequency power pre- sented no differences between patients and controls (p > 0.05). Sweat responses were significantly reduced in patients for all sites tested (forearm 0.389  1.309 mL; proximal leg 0.406  1.107 mL; distal leg 0.491  1.232 mL; foot 0.265  0.708 mL; p value < 0.05). Sweat volumes correlated with FARS scores. Conclusions: We found abnormal sudomotor but normal heart rate variability in FRDA. Small cholinergic post-ganglionic fibers are affected in the disease. Significance: Quantification of sudomotor function might be a biomarker for FRDA. Ó 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved. 1. Introduction Friedreich ataxia (FRDA) is considered the most prevalent auto- somal recessive ataxia worldwide with estimated prevalence of 3/100,000. The disease is common in Caucasian populations, but practically absent in sub-saharan regions and in the Far East. In 95% of the cases, the underlying cause is a homozygous expansion of a (GAA) repeat in intron 1 of FXN at 9q21.1 (Koeppen, 2011; Durr et al., 1996; Campuzano et al., 1996; Fogel and Perlman, 2007). This leads to a transcriptional abnormality that results in the lack of frataxin, a mitochondrial protein related to iron homeostasis (Campuzano et al., 1997). Neurological signs include ataxia, dysar- https://doi.org/10.1016/j.clinph.2018.08.017 1388-2457/Ó 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved. Abbreviations: FRDA, Friedreichs’s ataxia; FARS, Friedreich’s Ataxia Rating Scale; SCOPA-AUT, Scales for Outcomes in Parkinson’s Disease – Autonomic Question- naire; HRV, heart rate variability; E:I ratio, expiratory, inspiratory ratio; LF, low frequency band; HF, high frequency band; R30, maximum-to-minimum variation in deep breathing; QSART, quantitative sudomotor axonal reflex test; LFPA, low frequency power; HFPA, high frequency power; MIBG, meta-iodo benzylguanidine. ⇑ Corresponding author at: Department of Neurology, University of Campinas – UNICAMP, Rua Tessália Vieira de Camargo, 126, Cidade Universitaria ‘‘Zeferino Vaz”, Campinas, SP 13083-887, Brazil. E-mail address: mcfrancajr@uol.com.br (M.C. França). Clinical Neurophysiology 129 (2018) 2290–2295 Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph