Autonomic dysfunction in hereditary spastic paraplegia type 4.

Abstract

SPAST mutations are the most common cause of hereditary spastic paraplegia (SPG4-HSP), which is characterized by progressive lower limb weakness, spasticity and hyperreflexia. There are few studies about non-motor manifestations in this disease and none about autonomic involvement. Therefore, the aim was todetermine the frequency and pattern of autonomic complaints in patients with SPG4-HSP, as well as to determine the clinical relevance and the possible factors associated with these manifestations. Thirty-four molecularly confirmed SPG4 patients were recruited in a multicenter cross-sectional study, of whom 26 underwent detailed neurophysiological testing (heart rate variability, sympathetic skin response and the Quantitative Sudomotor Axonal Reflex Test). The Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire (SCOPA-AUT) was applied to quantify the severity of autonomic symptoms. Results were compared with 44 age- and gender-matched healthy controls using non-parametric tests. P values <0.05 were considered significant. In the SPG4-HSP group, there were 18 men with a mean age of 47.7±12.6years. SCOPA-AUT scores were similar between patients and controls (P=0.238). Only the urinary domain subscore was significantly higher amongst patients (4 vs. 2.5, P=0.05).Absent sympathetic skin response in the hands and feet was more frequent amongst patients (20% vs. 0%, P<0.001, and 64% vs. 0%, P=0.006, respectively). Quantitative Sudomotor Axonal Reflex Test responses were also smaller throughout all recording regions in the SPG4-HSP group. Our results indicate that SPG4-HSP patients have sudomotor dysfunction caused by damaged small post-ganglionic cholinergic fibers. Damage in SPG4-HSP extends to the peripheral nervous system.