Summary of evidence on frequently examined prognostic factors predicting survival
| Negative prognostic factor |
Total no. of studies |
Meta-analysis pooled HR (95% CIs) | Narrative synthesis | |||||
| Univariate HR | I2 | Multivariate HR* | I2 | No. of studies reporting a significant effect on survival | HRs (95% CIs) or other effect measures of studies reporting a significant effect on survival of the negative prognostic factor | |||
| PSP | PSP-RS (vs PSP-P phenotype) | 4 | 2.53 (1.69 to 3.78) | 18% | 2.37 (1.21 to 4.64) | n=1 | ||
| Early development of dysphagia | 4 | 4 | MV: 3.91 (1.39 to 11.0) MV: 2.84 (1.51 to 5.34) MV: 2.3 (1 to 5.3) 1.9 year difference median survival | |||||
| Early development of cognitive symptoms | 4 | 2 | MV: 3.6 (1.6 to 8.2) MV: 1.99 (1.17 to 3.38) | |||||
| Vertical supranuclear gaze palsy | 5 | 2 | MV: 2.74 (1.52 to 4.94) UV: 1.12 (1.10 to 1.31) | |||||
| MSA | MSA-P (vs MSA-C phenotype) | 8 | 1.12 (0.97 to 1.29) | 9% | 1.22 (0.83 to 1.80) | 19% | ||
| Severe dysautonomia: -Mild vs severe (2 studies) -CGI dysautonomia score (1 study) -CASS (2 studies) | 5 | 5 | 2.3-year difference median survival 3.5-year difference median survival MV: 1.41 (1.19 to 1.67) MV: 1.07 (1.02 to 1.11) MV: 2.8 (1.01 to 9.26) | |||||
| Development of dysautonomia within 1, 2 and 2.5 years of MSA onset | 3 | 3 | UV: 1.24 (1.04 to 1.49) MV: 6.0 (3.1 to 11.7) MV: 3.4 (1.61 to 7.15) | |||||
| Combined motor and autonomic symptoms within 3 years of MSA onset | 2 | 2 | UV: 2.65 (1.42 to 4.93) 3-year difference median survival | |||||
| Orthostatic hypotension | 2 | 1.24 (1.04 to 1.49) | 0% | 1.29 (1.07 to 1.56) | 0% | |||
| Dysautonomia present at MSA onset | 5 | 0 | NA | |||||
| Bladder symptoms | 5 | Conflicting results and heterogeneous definitions of prognostic factor | ||||||
| Stridor | 6 | 2 | MV comparing untreated stridor with no stridor: 3.0 (1.63 to 5.53) Reduced survival after 6 years as evident from the Kaplan Meier curve | |||||
| PSP and MSA | Male sex | 10 | 1.05 (0.95 to 1.18) | 32% | 0.93 (0.67 to 1.28) | 34% | ||
| Age at disease onset: -Above median age (9 studies) -Per year increase (6 studies) | 14 | 1.92 (1.50 to 2.44) 1.01 (1.0 to 1.02) | 0% 23% | 1.75 (1.32 to 2.32) 1.10 (0.98 to 1.23) | 63% 68% | |||
| Early onset of falls | 6 | 1.62 (0.55 to 4.77) | 87% | 2.32 (1.94 to 2.77) | 0% | |||
| Levodopa response | 4 | 0.87 (0.73 to 1.02) | 1% | 0.60 (0.31 to 1.14) | n=1 | |||
| NNIPPS Parkinson Plus Score | 1 | 1 | MV: 1.01 (1.01 to 1.02) | |||||
| Clinical Global Impression Disease Severity Score | 1 | 1 | MV: 1.28 (1.09 to 1.51) | |||||
| Hoehn and Yahr Staging Scale: -Overall score (2 studies) -Stage 5 (1 study) | 3 | 1 | MV stage 5: 12.45 (1.93 to 80.93) | |||||
| PSP Rating Scale | 2 | 2 | No effect sizes reported | |||||
| Unified MSA Rating Scale: -Overall score -Activities of Daily Living Subscore | 2 | 1 | Activities of Daily Living Subscore MV: 1.04 (1.01 to 1.07) | |||||
| Northwestern University Disability Score | 1 | 0 | NA | |||||
| Shorter interval between disease onset and first clinical milestone | 2 | 2 | UV: 3.4 (1.4 to 8.3) PSP MV: 1.25 (1.11 to 1.4) MSA MV: 1.72 (1.47 to 2.04) | |||||
A more detailed breakdown of results, including non-significant results, is available in the online supplementary material.
*Refers to HR derived by pooling HRs calculated by multivariate analysis in individual studies.
CASS, Composite Autonomic Scoring Scale; CI, confidence interval; MSA, multiple system atrophy; MSA-C, MSA-cerebellar; MSA-P, MSA-parkinsonism; MV, multivariate analysis; NNIPPS, Neuroprotection and Natural History in Parkinson Plus Syndromes; PSP, progressive supranuclear palsy; PSP-P, PSP-parkinsonism; PSP-RS, PSP-Richardson’s; UV, univariate analysis.