Tremor in multiple system atrophy: a systematic literature review

Up to 80% of patients with multiple system atrophy (MSA) exhibit tremor or tremor-like phenomena, yet the clinical features of these manifestations remain insufficiently characterized. Clearer phenotypic delineation may support differential diagnosis from other tremor-associated disorders, particularly Parkinson's disease (PD). We aimed to determine characteristics and prevalence of tremor, distribution across MSA phenotypes and body regions, and its treatment responsiveness. We systematically searched PUBMED for articles reporting tremor in MSA, following PRISMA guidelines. Eligible studies were screened, with data reviewed by two reviewers and risk of bias assessed using JBI critical appraisal tools. Of 127 records, 25 studies met inclusion criteria, comprising 963 MSA patients. Tremor types and prevalence differed by phenotype. In MSA-P, rest tremor occurred in 26.5-38.1% and action tremor in 60.3-81.8%. In MSA-C, rest tremor occurred in 11-22.5%, action tremor in 44.9-97.5%. Among action tremor, a 3-Hz pseudo-orthostatic tremor occurred more often in MSA-C (76.3-97.5%) than MSA-P (24.1-38.3%). Polyminimyoclonus was present in 16.5% of MSA-P and 10.5% of MSA-C. Neurophysiologically, MSA-C typically showed ~ 3-Hz pseudo-orthostatic tremor, whereas MSA-P presented a 7-8-Hz postural tremor and 5-6-Hz rest tremor. Levodopa improved tremor in 11.8-92% of cases, with benefit more often in MSA-P and in action tremor. Preliminary reports suggest potential benefit of clonazepam and botulinum toxin, while a pilot high intensity focused ultrasound therapy showed no improvement. This first systematic review demonstrates that tremor in MSA is common and phenotypically diverse. Rest tremor is generally less frequent than action tremor and a 3-Hz pseudo-orthostatic tremor is characteristic of MSA-C.