- Multiple system atrophy (MSA) is a rare, progressive neurodegenerative disorder characterized by a combination of autonomic dysfunction, parkinsonism, and cerebellar ataxia. It affects multiple systems in the central nervous system, including those controlling movement, balance, and involuntary bodily functions such as blood pressure regulation, bladder control, and digestion. MSA is considered a synucleinopathy, meaning it involves the abnormal accumulation of alpha-synuclein protein in the brain, particularly within oligodendrocytes—the support cells of the nervous system—rather than neurons, as in Parkinson’s disease.
- There are two main subtypes of MSA based on predominant symptoms:
- MSA-P (Parkinsonian type): marked by symptoms similar to Parkinson’s disease, including muscle rigidity, bradykinesia (slowness of movement), postural instability, and sometimes tremor.
- MSA-C (Cerebellar type): dominated by cerebellar ataxia, leading to issues with coordination, balance, speech, and gait.
- A hallmark feature of MSA is autonomic failure, which often manifests early and may include orthostatic hypotension (a drop in blood pressure upon standing), urinary incontinence or retention, erectile dysfunction, constipation, and sweating abnormalities. These symptoms often precede the more noticeable motor impairments and are critical for distinguishing MSA from other neurodegenerative diseases.
- The exact cause of MSA remains unknown, and no clear genetic or environmental risk factors have been definitively identified, although research into potential genetic contributors and environmental exposures is ongoing. The pathology is defined by glial cytoplasmic inclusions—abnormal deposits of alpha-synuclein in oligodendroglial cells—which are believed to trigger widespread neural dysfunction and degeneration.
- Diagnosis of MSA is based on clinical criteria supported by neuroimaging (such as MRI), which may reveal characteristic features like atrophy of the cerebellum, pons, or putamen, and signs such as the “hot cross bun” sign in the brainstem for MSA-C. Definitive diagnosis can only be made through neuropathological examination after death. Because MSA shares features with Parkinson’s disease and other atypical parkinsonian syndromes, misdiagnosis is common in early stages.
- There is currently no cure for MSA, and treatment is symptomatic and supportive. For motor symptoms, levodopa may be tried, but its effects are often minimal and short-lived compared to Parkinson’s disease. Autonomic symptoms may be managed with medications to raise blood pressure (e.g., fludrocortisone, midodrine), catheterization or medications for urinary dysfunction, and dietary modifications. Physical therapy, speech therapy, and occupational therapy play important roles in maintaining function and quality of life.
- MSA progresses rapidly compared to Parkinson’s disease, with median survival ranging from 6 to 10 years after symptom onset. The course typically involves increasing disability, with most patients requiring assistance with daily activities within a few years. Respiratory complications, including vocal cord paralysis or aspiration pneumonia, and sudden death due to autonomic instability, are common causes of mortality.
