Increased Plasma Catecholamines in Patients with Friedreich’s Ataxia

Abstract

SUMMARY:We studied free plasma catecholamines in 23 patients with Friedreich’s ataxia, having a mean age of 22 ± 9.6 (SD) years. Conjugated catecholamines were also studied in 10 patients. Mean plasma norepinephrine and epinephrine were significantly higher than controls both in the supine and standing positions. In total 15 out of 23 patients (65%) had increased free and/or conjugated plasma catecholamines. The increase in plasma catecholamines was more marked in patients with severe neuromotor impairment. Among the patients with left ventricular concentric hypertrophy (wall thickness >12 mm), only 3 had no demonstrable sympathetic hyperfunction.Since the high local concentrations of norepinephrine at the site of release from sympathetic nerve terminals may serve as a trigger for the hypertrophic response of the myocardial cell, it is suggested that early pharmacological intervention could prevent or limit the cardiomyopathic process or its clinical consequences.

Autonomic function in Friedreich's ataxia.

“…Detailed descriptions of these studies have been published.6 A) Noninvasive Tests 1 Valsalva ratio 2 Heart rate variation with respiration a) Sinus arrhythmia b) Expiratory: Inspiratory ratio (E:I ratio) 3 Heart rate response to standing (30:15 ratio) 4 Cardiovascular changes with tilting a) Systolic blood pressure b) Diastolic blood pressure c) Heart rate 5 Change in diastolic blood pressure with isometric exercise 6 Plasma noradrenaline studies a) Supine plasma noradrenaline levels b) Percentage increase in plasma noradrenaline after tilting 7 Sweat test B) Studies using intra-arterial blood pressure recording 1 Valsalva manoeuvre 2 Baroreceptor sensitivity Informed consent was obtained from each patient and the protocol for the investigations of autonomic function was approved by the Medical Ethics Committee of the University of Sydney. Statistical Analysis Data from the control subjects were examined for skewness and outliers.…”

Coronary disease, cardioneuropathy, and conduction system abnormalities in the cardiomyopathy of Friedreich's ataxia.

“…38 Cardioneuropathy may also affect myocardial contractility. The inevitable regional variations in the neural inotropic influence may be the basis of some of the unusual changes in segmental wall motion or other ventricular contractile abnormalities described in Friedreich's cardiomyopathy.13- 16 [20][21][22][23][24][25][26][27][28][29] There is not much dispute about the general nature of the myocardial lesions: hypertrophy of fibres, widely scattered focal degeneration and varying degrees of fibrosis, and the unusual nuclear abnormalities first described by Russell. Hypertrophy of the heart is generalised, as are each of the myocardial lesions.…”