Autonomic failure: a neglected presentation of Parkinson's disease

Neurogenic orthostatic hypotension is a fall in blood pressure upon standing due to sympathetic autonomic failure, which can cause orthostatic intolerance and syncope. Pure autonomic failure is a sporadic disorder traditionally defined by the presence of idiopathic neurogenic orthostatic hypotension, usually with signs of neurogenic bladder and bowel dysfunction, but no other neurological features. 1 The Consensus Committee of the American Autonomic Society and the American Academy of NeurologyConsensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology. 1996; 461470 Crossref PubMed Scopus (974) Google Scholar Neuropathological findings of α-synuclein aggregates in the brainstem and skin autonomic fibres of affected people led researchers to interpret pure autonomic failure as a peculiar α-synucleinopathy limited to the autonomic nervous system, but studies in the past 5 years provided a substantial paradigm shift in our understanding of this disorder. 2 Kaufmann H Norcliffe-Kaufmann L Palma JA et al. Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol. 2017; 81: 287-297 Crossref PubMed Scopus (148) Google Scholar , 3 Giannini G Calandra-Buonaura G Asioli GM et al. The natural history of idiopathic autonomic failure: the IAF-BO cohort study. Neurology. 2018; 91: e1245-e1254 Crossref PubMed Scopus (14) Google Scholar , 4 Coon EA Mandrekar JN Berini SE et al. Predicting phenoconversion in pure autonomic failure. Neurology. 2020; 95: e889-e897 Crossref PubMed Scopus (10) Google Scholar Up to a third of people with pure autonomic failure develop another α-synucleinopathy, including Parkinson's disease, suggesting that pure autonomic failure might in fact be a premotor presentation thereof. 2 Kaufmann H Norcliffe-Kaufmann L Palma JA et al. Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol. 2017; 81: 287-297 Crossref PubMed Scopus (148) Google Scholar , 3 Giannini G Calandra-Buonaura G Asioli GM et al. The natural history of idiopathic autonomic failure: the IAF-BO cohort study. Neurology. 2018; 91: e1245-e1254 Crossref PubMed Scopus (14) Google Scholar , 4 Coon EA Mandrekar JN Berini SE et al. Predicting phenoconversion in pure autonomic failure. Neurology. 2020; 95: e889-e897 Crossref PubMed Scopus (10) Google Scholar Importantly, people with pure autonomic failure who progress to Parkinson's disease show a peripheral pattern of lesions in the autonomic nervous system. 2 Kaufmann H Norcliffe-Kaufmann L Palma JA et al. Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol. 2017; 81: 287-297 Crossref PubMed Scopus (148) Google Scholar , 4 Coon EA Mandrekar JN Berini SE et al. Predicting phenoconversion in pure autonomic failure. Neurology. 2020; 95: e889-e897 Crossref PubMed Scopus (10) Google Scholar Parkinson's disease outside the brain: targeting the autonomic nervous systemPatients with Parkinson's disease present with signs and symptoms of dysregulation of the peripheral autonomic nervous system that can even precede motor deficits. This dysregulation might reflect early pathology and therefore could be targeted for the development of prodromal or diagnostic biomarkers. Only a few objective clinical tests assess disease progression and are used to evaluate the entire spectrum of autonomic dysregulation in patients with Parkinson's disease. However, results from epidemiological studies and findings from new animal models suggest that the dysfunctional autonomic nervous system is a probable route by which Parkinson's disease pathology can spread both to and from the CNS. Full-Text PDF