Early Distinction of Parkinson-Variant Multiple System Atrophy from Parkinson’s Disease
Alessandra Fanciulli, MD PhD, et al
Distinguishing the Parkinson variant of MSA (MSA-P) from Parkinson’s disease (PD) is often difficult at disease onset. This is a major drawback for counseling of patients and timely enrollment into disease-modifying clinical trials.
Clinicopathological studies consistently report that postural instability and autonomic failure emerge earlier in MSA-P than in PD,2,3 but it remains to be determined how this information can be integrated into the diagnostic work-up of patients with early parkinsonism.
Here, we aimed at (1) quantifying the diagnostic yield of early-onset postural instability as well as cardiovascular and urological autonomic failure in differentiating MSA-P from PD and (2) merging early MSA-P distinctive features into a MSA-P diagnostic probability score.
For this purpose, we retrospectively studied 161 PD and 29 MSA-P patients, who had undergone tilt-table testing at early disease, defined as Hoehn & Yahr (H&Y) stage <3 and/or disease duration <2 years. In the absence of neuropathological confirmation, established PD4 and MSA-P5 criteria were applied at last available visit by senior investigators and served as the clinical diagnostic gold standard. The diagnosis was further supported by cerebral MRI volumetry6 in all MSA-P patients with available MRI (n = 21) and in those PD patients with a follow-up time < 24 months and disease duration <5 years (n = 19): patients with a mismatch between the final clinical and MRI diagnosis were excluded from further analysis (n = 4). Clinical features at early disease, associated with a diagnosis of MSA-P at last available visit, were investigated by means of χ2, parametric, and nonparametric tests, followed by binary logistic regression analysis. An MSA-P diagnostic probability score was generated on the basis of early MSA-P discriminant variables. The study protocol was approved by the local ethical committee and performed according to the Declaration of Helsinki. Because of the retrospective design, no written informed consent was due. Processing of data followed the current Austrian regulation for data protection. By taking into account all significantly different clinical demographic traits at early disease, logistic regression analysis showed the following features to be associated with a final diagnosis of MSA-P: (1) postural instability (H&Y stage ≥3) within 2 years from disease onset; (2) orthostatic hypotension7; (3) symptoms of overactive bladder (urge and/or urinary incontinence); and (4) urinary retention (i.e., postvoid residual urine volume > 100 mL).
By assigning 1 point per above-mentioned feature, a cumulative score ≥ 2 (score range: 0-4) showed 78% sensitivity (95% confidence interval [CI]: 58-91), 86% specificity (95% CI: 80-91), 50% positive predictive value (95% CI: 39-61), and 96% negative predictive value (95% CI: 91-98) for a final diagnosis of MSA-P. The area under the receiver operating characteristic (ROC) curve was 0.884 (95% CI: 0.823-0.946).
We conclude that postural instability and autonomic failure manifest in both PD and MSA-P, but their early development indicates MSA-P.
The 4-points MSA-P diagnostic probability score shows a balanced sensitivity and specificity for early MSA-P and represents an easily accessible, cost- and time-effective tool for screening parkinsonian patients with low or absent MSA risk (0–1 point) from those with high MSA-risk (2–4 points). The latter may benefit from referral to specialized movement disorder centers and, ultimately, recruitment in ongoing neuroprotective studies.