Association of autonomic symptoms with disease progression and survival in progressive supranuclear palsy

Abstract

BackgroundDevelopment of autonomic failure is associated with more rapid disease course and shorter survival in patients with Parkinson’s disease and multiple system atrophy. However, autonomic symptoms have not been specifically assessed as a prognostic factor in progressive supranuclear palsy (PSP). We evaluated whether development of autonomic symptoms is associated with disease progression and survival in PSP.MethodsA retrospective review of clinical data from consecutive patients with autopsy-confirmed PSP from the Queen Square Brain Bank between January 2012 and November 2016 was performed. Time from disease onset to four autonomic symptoms (constipation, urinary symptoms, erectile dysfunction and orthostatic hypotension) were noted. Time from diagnosis to five disease milestones and survival were calculated to assess disease progression, and their risk was estimated through a Cox proportional hazards model.ResultsA total of 103 PSP patients were included. Urinary symptoms and constipation were present in 81% and 71% of cases, respectively. Early development of constipation and urinary symptoms were associated with higher risk of reaching the first disease milestone (respectively, HR: 0.88; 95% CI 0.83 to 0.92; p<0.001; and HR: 0.80; 95% CI 0.75 to 0.86; p<0.001) and with a shorter survival in these patients (respectively, HR: 0.73; 95% CI 0.64 to 0.84; p<0.001; and HR: 0.88; 95% CI 0.80 to 0.96; p=0.004). On multivariate analysis, Richardson syndrome phenotype was the other variable independently associated with shorter survival.ConclusionsEarlier urinary symptoms and constipation are associated with a more rapid disease progression and reduced survival in patients with PSP.

Natural clinical course of progressive supranuclear palsy in Chinese patients in Hong Kong

“…1,2,[5][6][7][8][9][10][11][12][13][14][15][16][17][23][24][25][26][27][28] With regard to clinical features, our cohort of patients exhibited early development of motor symptoms, which was consistent with previous studies. 1,2,[5][6][7][8][9][10][11][12][13][14][15][16][17][23][24][25][26][27][28] Our cohort of patients showed evidence of improved mobility, as reflected by changes in elderly mobility scale score after training in the geriatric day hospital, with a median time to referral of 20 months from the initial clinical presentation. Patients with PSP should be referred to a physiotherapist and an occupational therapist for fall assessment, as well as guidance regarding the potential need for walking aids.…”

“…5 Other predictors of mortality found in the present study, including vertical gaze palsy, dysphagia, pneumonia, or pressure injuries, were previously reported in other studies. [6][7][8][9][10][11][12][13][14][15][16] It remains unknown whether resolution of dysphagia in patients with PSP can prevent pneumonia and reduce mortality. It is important for clinicians to refer patients with PSP involving dysphagia to a speech therapist for advice regarding food texture and appropriate swallowing posture (ie, chin-tuck) [ Table 4].…”

“…5 Factors predictive of mortality included age at onset, early clinical milestones (eg, falls, vertical gaze palsy, neck or limb stiffness, dysphagia, and incontinence), cognitive impairment, language impairment, autonomic dysfunction, male sex, and certain subtypes of PSP, such as classical Richardson's syndrome and pneumonia. [6][7][8][9][10][11][12][13][14][15][16] To the best of our knowledge, there have been no studies of the natural clinical course of disease in Chinese patients with PSP. This information is important for clinical treatment and the design of future intervention studies (eg, for the purposes of sample size estimation).…”

Association of MRI Measures With Disease Severity and Progression in Progressive Supranuclear Palsy

“…Thus, the following milestones were selected to define disease progression: (1) dependence on wheelchair; (2) unintelligible speech; (3) dementia (i.e., cognitive impairment severe enough to significantly affect activities of daily living). These milestones have been selected because they are clinically relevant and represent the different domains of impairment of functioning in PSP (14,15). All enrolled patients but 5 were re-evaluated after a mean (standard deviation) of 16.36 (11.51) months.…”

Can Autonomic Testing and Imaging Contribute to the Early Diagnosis of Multiple System Atrophy? A Systematic Review and Recommendations by the Movement Disorder Society Multiple System Atrophy Study Group

“…The presence of nOH is specific for MSA versus PSP and corticobasal degeneration (CBD), particularly in the early stages. Specificity ranges from 85% to 100%, but sensitivity is low in early disease (21%) 4,63–66 . The presence of nOH is of limited usefulness to distinguish MSA versus DLB 4,5 …”