Autonomic nervous system dysfunction in Wilson's disease - A systematic literature review

In Wilson's disease (WD), copper accumulation can result in neurological manifestations, particularly extrapyramidal symptoms. There are some data that the autonomic nervous system (ANS) may also be affected, and we aimed to systematically review available studies evaluating ANS dysfunction in WD.

We conducted a systematic review of the literature using the PubMed database (up to 31st August 2020), with search terms including "autonomic" and "function" and "Wilson's disease".

Fourteen studies, including 297 patients with neurological, hepatic or psychiatric forms of WD were retrieved. The most frequent methods used for ANS evaluation were orthostatic tests, which were performed in seven studies, with a number of other tests less frequently used. The incidence of ANS abnormalities ranged from ~8% to 79.2%, depending on the evaluation method. ANS abnormalities in patients with WD were often clinically asymptomatic. The features of dysautonomia were more common among patients with neurological symptoms and ANS abnormalities were more common in patients with severe brain injury. Studies confirmed both sympathetic and parasympathetic ANS impairment. The pathophysiology of ANS damage was not clear but may result from central, peripheral nervous system and direct cardiac involvement. Clear improvements were observed in four studies after anti-copper therapy initiation.

Both sympathetic and parasympathetic divisions of the ANS may be affected in WD. The observed ambiguities regarding ANS abnormalities in WD patients may arise from small study groups, differences in methodology, and a lack of comprehensive ANS evaluation; however, the results indicate that further studies are warranted.