Survival in synucleinopathies: A prospective cohort study

Area of Science:

• Neurology
• Neuroscience
• Clinical Medicine

Background:

• Synucleinopathies like Parkinson disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) are characterized by α-synuclein deposition.
• Neurogenic orthostatic hypotension (OH) is prevalent in these conditions, affecting approximately 40% of PD patients, most MSA patients, and all PAF patients.

Purpose of the Study:

• To compare long-term survival rates among patients diagnosed with PD (with and without OH), MSA (cerebellar and parkinsonian subtypes), and PAF.
• To determine the prognostic impact of different synucleinopathies and the presence of OH on patient survival.

Main Methods:

• A prospective cohort study involving 206 referred patients evaluated between 1994 and 2014.
• Survival data were collected for 97.6% of patients, with diagnoses confirmed through clinical criteria and specialized tests.
• The Cox proportional hazard model was employed to analyze survival from symptom onset and evaluation time to death.

Main Results:

• Patients with MSA (cerebellar [MSA-C] or parkinsonian [MSA-P]) exhibited significantly shorter survival from symptom onset compared to PD + OH, PAF, and PD no OH groups (HRs ranging from 5.6 to 14.9, p < 0.0001).
• Median survival from motor onset to death was 7.5 years for MSA-P, 11.6 years for PD + OH, and 15.8 years for PD no OH.
• Ten-year survival probabilities from symptom onset were notably lower for MSA-C (0.39) and MSA-P (0.33) compared to PD + OH (0.74), PAF (0.87), and PD no OH (0.93).

Conclusions:

• Survival outcomes in synucleinopathies are disease-specific.
• Multiple System Atrophy-parkinsonian (MSA-P) presents a higher mortality risk than Parkinson disease with orthostatic hypotension (PD + OH).
• Parkinson disease with orthostatic hypotension (PD + OH) carries a greater mortality risk than Parkinson disease without orthostatic hypotension (PD no OH).