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New treatments hold great promise for neurodegenerative disorders such as the synucleinopathies, including pharmacologic, mechanical (deep brain and cortical stimulation, growth factor infusion), and cell-based and gene therapies.1,2 A number of nonmotor signs and symptoms may be present long before the appearance of typical clinical features (table). This prodromal phase has been referred to as the presymptomatic, subclinical, preclinical, or premotor period, which may range from 4 to 6 years, and is thought to be related to nondopaminergic lower brainstem structures or autonomic plexuses. However, the article by Claassen et al.3 in this issue of Neurology® extends that interval to half a century for REM sleep behavior disorder (RBD) as a harbinger for synucleinopathies (Parkinson disease [PD], multiple system atrophy, pure autonomic failure, and dementia with Lewy bodies).
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Table Early nonmotor harbingers of synucleinopathies
IMPLICATIONS FOR EARLY DIAGNOSIS AND DETECTION OF SYNUCLEINOPATHIES
Human RBD was at one time an isolated observation—simply the consequence of REM sleep without atonia (RWA). Follow-up of middle-aged and older patients with “idiopathic” RBD revealed, however, a surprise: some patients with RBD, after nearly 2 decades, developed PD, with increasing percentages of patients with RBD manifesting some …
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