By Santiago Perez et al. in Movement Disorders Clinical Practice February 2, 2015

Abstract: MSA is a progressive neurodegenerative disorder characterized by autonomic failure and a variable combination of poor levodopa‐responsive parkinsonism and cerebellar ataxia (CA). Current therapeutic management is based on symptomatic treatment. Almost one third of MSA patients may benefit from l‐dopa for the symptomatic treatment of parkinsonism, whereas physiotherapy remains the best therapeutic option for CA. Only midodrine and droxidopa were found to be efficient for neurogenic hypotension in double‐blind, controlled studies, whereas other symptoms of autonomic failure may be managed with off‐label treatments. To date, no curative treatment is available for MSA. Recent results of neuroprotective and ‐restorative trials have provided some hope for future advances. Considerations for future clinical trials are also discussed in this review.

Autonomic failure, depression, and motor symptoms strongly correlate with poor quality of life,2 thus making them the main target for symptomatic therapy. Median survival ranges between 6 and 9 years after symptom onset,5 with nocturnal sudden death and aspiration pneumonia being major causes of death, as indicated by one small study.6 No treatment has yet been shown to improve survival in MSA, creating a strong need for new therapeutic approaches.

The pathological hallmark of MSA is the accumulation of alpha‐synuclein (α-Syn) within glial cytoplasmic inclusions (GCIs).7 GCIs also contain many other proteins, suggesting that additional mechanisms are contributing to the progressive neurodegenerative process.8 The most consistently and severely affected brain regions are the olivopontocerebellar and striatonigral systems. In most cases, cell loss predominates in one of these systems, which is consistent with the clinical distinction between MSA‐P and MSA‐C.

In this article, we aimed at updating data on symptomatic and preventive/curative approaches for the management of MSA, based on our previous review article published in 2010.9 Some considerations will also be discussed regarding clinical trials in this population.