Finger Cold-Induced Vasodilatation, Sympathetic Skin Response, and R—R Interval Variation in Patients With Progressive Spinal Muscular Atrophy

Abstract

To elucidate autonomic function in spinal muscular atrophy, we evaluated finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation in 10 patients with spinal muscular atrophy: 7 of type 1, 2 of type 2, and 1 of type 3. Results of finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation were compared with those of healthy children. Finger cold-induced vasodilatation was abnormal in 6 of 10 patients with spinal muscular atrophy; it was normal in the healthy children. The mean sympathetic skin response latency and amplitude did not differ significantly from those of the healthy children. Amplitudes of sympathetic skin response to sound stimulation were absent or low in all six patients with spinal muscular atrophy. No significant difference was found in the mean R-R interval variation of patients with spinal muscular atrophy and healthy children. Results show that some patients with spinal muscular atrophy have autonomic dysfunction, especially sympathetic nerve hyperactivity, that resembles dysfunction observed in amyotrophic lateral sclerosis.

Vascular Perfusion Abnormalities in Infants with Spinal Muscular Atrophy

“…11 Arai et al 11 performed autonomic investigations in a small cohort of children with SMA, including 7 infants with type I, 2 infants with type II, and 1 child with type III, and compared them with results obtained in healthy children. Investigations included finger cold–induced vasodilation, sympathetic skin response, and R-R interval variation.…”

“…No significant difference was found in the mean R-R interval variation. Arai et al 11 documented autonomic dysfunction in 3 cases of SMA type 1 on long-term mechanical ventilation, and demonstrated sympathetic-vagal imbalance on R-R interval analysis, as well as abnormalities in finger cold–induced vasodilation. One case showed significant blood pressure and heart rate fluctuation, as well as a high plasma concentration of norepinephrine during tachycardia.…”

Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

“…Autonomic dysfunction and, particularly sympathetic dysfunction, has been hypothesized to be a primary source of the vascular perfusion abnormalities in SMA [134]. Vascular defects include coolness and poor perfusion of distal extremities; and occasional digital necrosis has been reported in SMA type I children [122].…”

Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model

“…Supplying the therapeutic ASO to the CNS restored cellular SMN levels, which in turn might prevent the deterioration of motor neurons and consequent muscle atrophy. Another possible scenario is that distal necrosis in SMA patients and mouse models may result from vascular perfusion abnormalities related to autonomic nervous system dysfunction (Arai et al 2005;Araujo Ade et al 2009). It remains to be seen whether sympathetic and parasympathetic nervous system functions are affected by limiting SMN protein.…”