A Systematic Review of the Spectrum and Prevalence of Non-motor Symptoms in Multiple System Atrophy

Background Patients with Multiple System Atrophy (MSA) frequently report non-motor symptoms, and several research groups have highlighted this. Objective We systematically searched for and reviewed papers assessing prevalence of non-motor symptoms (NMS) in MSA patients as reported in the scientific literature. Methods We performed a systematic review of studies of subjects with MSA (involving > 10 patients) who were assessed for NMS, published in the English literature in PUBMED and EMBASE databases from 1947-2022. Results 23 research papers, with data from 2648 clinically diagnosed and 171 pathologically verified cases of MSA were included, along with 238 controls. Mean age for MSA cases was 61.3 (9.2) years, mean disease duration 3.6 (2.7) years. 57.9% were male. Our analysis showed that the prevalence of cognitive issues in MSA varied widely (between 15-100%); dementia per se was uncommon, but assessment in advanced stages of MSA is impacted by unintelligible speech (which may be noted in a quarter of cases). The prevalence of depressive symptoms in MSA was between 44-88%. Sleep disturbances were reported by 17-89%, with REM-sleep behaviour disorder (RBD) rates as high as 75%. Pain was reported by 40-47% of patients: rheumatic or musculoskeletal sources of pain being commonest. Fatigue was reported by 29-60% of patients. Symptoms of autonomic failure in MSA were seen in 34-96.5% patients at baseline. Conclusion In routine clinical practice, NMS in MSA are under-recognised by clinicians. These impact hugely on patient quality of life and contribute to their overall morbidity. A methodical ascertainment of these complaints will address an unmet need, and lead to a more holistic approach of care for individuals with MSA.