Prodromal autonomic symptoms and signs in Parkinson's disease and dementia with Lewy bodies.

Mov Disord. 2013 Mar 28. doi: 10.1002/mds.25445. [Epub ahead of print]

Postuma RB, Gagnon JF, Pelletier A, Montplaisir J.

Source

Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada; Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada.

Abstract

Pathologic staging systems suggest that autonomic dysfunction may be an early manifestation of Parkinson's disease and dementia with Lewy bodies. However, direct evidence is limited, and no prospective studies have measured when autonomic dysfunction starts before disease. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder are at very high risk of developing neurodegenerative synucleinopathy, providing an opportunity to directly observe the development of autonomic dysfunction from prodromal stages of neurodegeneration. Patients with idiopathic REM sleep behavior disorder were followed annually in a prospective cohort that was established in 2004. Urinary, orthostatic, erectile, and constipation symptoms and systolic blood pressure drop from lying to standing were assessed annually. Patients who eventually developed defined synucleinopathy were compared with age-matched controls. The evolution of autonomic measures was assessed with regression analysis to determine when markers first deviated from control values. Sensitivity and specificity of autonomic markers for identification of prodromal disease were calculated. Of 91 patients, 32 developed disease. In prodromal stages, there was substantial autonomic dysfunction observable at least 5 years before diagnosis. On regression analysis, autonomic dysfunction appeared to progress slowly over prodromal periods. The estimated onset of autonomic dysfunction ranged from 11 years to 20 years, and systolic drop (20.4 years) and constipation (15.3 years) had the earliest estimates. Systolic drop, erectile dysfunction, and constipation could identify disease up to 5 years before diagnosis with sensitivity ranging from 50% to 90%. By directly observing development of neurodegenerative synucleinopathy, we confirmed that autonomic dysfunction can occur early in neurodegenerative synucleinopathy, even as long as 20 years before defined disease.