Objective: To investigate the autonomic function in Friedreich´s ataxia (FRDA)  

Background: FRDA is a hereditary neurodegenerative disorder characterized by progressive gait ataxia, limb dysmetria, dysarthria and peripheral neuropathy. Further features are hypertrophic cardiomyopathy and diabetes mellitus. The disease is caused by an intronic GAA expansion in the FXN gene. Age at onset and disease severity strongly correlates with the length of the shorter GAA repeat (GAA1). The neurodegeneration in FRDA primarily involves the dorsal root ganglia and large myelinated fibers in peripheral sensory nerves. Recently an involvement of small unmyelinated fibers has been demonstrated in skin biopsy of FRDA and it has been correlated with disturbances in temperature and pain perception. The presence of autonomic correlates was not investigated yet in genetically confirmed cases.    

Methods: Sixteen genetically confirmed FRDA patients were consecutively enrolled. Each patient underwent a general and neurological examination, laboratory work-up, ECG and echocardiography to rule out cardiomyopathy. Disease severity was quantified through SARA and ADL scales. The SCOPA-aut questionnaire was administered to evaluate autonomic symptoms. Autonomic function was investigated by means of a cardiovascular tests battery (head-up tilt, active standing, Valsalva maneuver and deep breathing) and of the skin sympathetic reflex. Results were compared to normative values of our laboratory.

Results: Mean age at examination was 42±14 years while the mean age at disease onset was 22±14. The average GAA1 length was 429±278 repeats. The mean SCOPA-aut score was 12±6. Six patients performed just one autonomic test because of cardiomyopathy and/or severe physical disabilities. Of the other 10 patients 40% had ≥2 abnormal autonomic tests including blunted deep breathing and Valsalva ratio, absent skin sympathetic reflex and delayed orthostatic hypotension in 1 case. No difference regarding age at examination, disease duration or severity, GAA1 repeats, and occurrence of impaired glucose tolerance was found in the comparison between the two groups.

Conclusions: We observed subtle alterations of autonomic function in our FRDA cohort independently from disease severity and occurrence of diabetes. That could be attributed to multiple determinants as well as to an impairment of peripheral autonomic relays.

References: Nolano, M., V. Provitera, C. Crisci, A. M. Saltalamacchia, G. Wendelschafer-Crabb, W. R. Kennedy, A. Filla, L. Santoro and G. Caruso (2001). “Small fibers involvement in Friedreich’s ataxia.” Ann Neurol 50(1): 17-25

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-autonomic-nervous-system-in-friedreichs-ataxia-preliminary-findings/