P.122 - Autonomic nervous system involvement in spinal muscular atrophy type 1, 2 and 3

Abstract

Spinal muscular atrophy (SMA) is a selective lower motor neuron disease. There are emerging data indicating the involvement of additional systems, such as the autonomic nervous system (ANS), in SMA 1. The main reported symptoms are tremors and sweating with a correlation with the severity of clinical phenotype. We studied 30 patients with type 1, 2 and 3 SMA (n:10 for each group), with a broad age range and followed regularly in a multidisciplinary setting. We evaluated also age- and sex-matched healthy controls. Symptoms of autonomic dysfunction were assessed using the Composite autonomic symptom scale (COMPASS 31) and specific autonomic tests. They comprise of: Head-up tilting (HUT), Valsalva manoeuvre, deep breathing and cold pressure tests and skin sympathetic reflex. Moreover, we tested the plasma and urinary levels of catecholamines and sudomotor dysfunction with the novel Sudoscan technique. A significant number of patients/caregivers (26/30) reported symptoms of ANS dysfunction, mainly with gastrointestinal involvement. Eleven patients could perform a complete HUT test, the other patients were evaluated on reaching the sitting position from supine due to severe lower limbs contractures. All patients with type 1 SMA and most of patients with type 2 SMA experienced orthostatic intolerance symptoms during tilt test. Moreover, we showed high supine level of epinephrine at baseline and no significant rising of norepinephrine after tilt compared to controls. At variance, the dosage of catecholamines on the 24-hour urine protein test did not confirm differences with controls. Only in the less severe patients (8/30), we were able to perform Valsalva manoeuvre, deep breathing and cold pressure tests, showing normal results. Skin sympathetic reflex and Sudoscan test were normal. Our results suggest the novel hypothesis that SMA patients may have an adrenergic hyperactivity, experiencing several symptoms ranging from tremors to orthostatic intolerance. Further studies on larger cohorts are needed to confirm these interesting results.