Involvement of the autonomic nervous system in the pathophysiology of Rett syndrome

Clinical observations and physiological evidence suggest involvement of the autonomic nervous system (ANS) in Rett syndrome (RS). We studied sympathetic skin response (SSR) and sleep-wakefulness-rhythm (SWR) in patients with RS and discussed involvement of the ANS in reference to the pathophysiology. The age dependent alteration in the parameters in SSR was suggested. Some patients showed absence of SSR and some showed asymmetric involvement of the parameters of the SSR, which suggested involvement of the ANS at a peripheral level and possible influences from higher centers. The asymmetry correlated with side of the scoliosis, but not with handedness or position of the hand on stereotypy. In reference to the scoliosis of RS, asymmetrical involvement of dopamine neurons is suggested, but reduced secretion of melatonin was proposed and possible influence of the sympathetic nervous system for it was discussed. Long lasting abnormalities of SWR as well as leakage of axial atonia into NREM stage are due to an early involvement of noradrenergic neurons. The latter implied the loss of integration of the central ANS. Based on these observations and references, it was speculated that the ANS is involved in RS at various levels from the central to peripheral nervous system.