What is Multiple System Atrophy (MSA)?

From the Guidelines

Multiple system atrophy (MSA) is a rare, progressive neurodegenerative disorder that should be diagnosed and managed by a neurologist specializing in movement disorders, with a focus on symptom management and maintaining quality of life, as there is no cure for the condition. MSA is characterized by a combination of symptoms affecting movement, blood pressure, and other body functions, occurring when nerve cells in specific areas of the brain deteriorate over time 1. The condition typically presents with parkinsonism (slow movement, stiffness, tremor), cerebellar ataxia (coordination problems), and autonomic dysfunction (issues with blood pressure regulation, bladder control, and sexual function).

Key Characteristics of MSA

• MSA can be subdivided into three distinct clinical subtypes: MSA-P (striatonigral degeneration), MSA-C (olivopontocerebellar atrophy), and MSA-A (Shy-Drager syndrome) 1
• The majority of cases of MSA exhibit Parkinsonian symptoms at some stage of the disease, with cerebellar ataxia, pyramidal signs, and dysautonomia (including urinary incontinence) frequently reported 1
• The typical onset is 55 to 65 years of age with a mean disease duration of almost 6 years 1

Management and Treatment

• Medications like levodopa may help with movement problems, though often with limited effectiveness 1
• Fludrocortisone or midodrine might be prescribed for blood pressure regulation 1
• Physical therapy, speech therapy, and occupational therapy are important supportive measures to maintain quality of life
• Early diagnosis and comprehensive symptom management are essential for maintaining quality of life, as the disease typically progresses more rapidly than Parkinson's disease, with most patients requiring significant assistance within 5-8 years of diagnosis 1

Prognosis

• The average survival from symptom onset is approximately 7-10 years 1
• Comprehensive management by a neurologist specializing in movement disorders is crucial to improve morbidity, mortality, and quality of life outcomes in patients with MSA.

From the Research

Definition and Characteristics of Multiple System Atrophy

• Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure, parkinsonism, and cerebellar ataxia 2, 3, 4, 5, 6
• The disorder is dominated by autonomic/urogenital failure, which may be associated with either levodopa unresponsive parkinsonism or cerebellar ataxia 6
• MSA is a synucleinopathy, with the accumulation of aggregated α-synuclein in oligodendrocytes forming glial cytoplasmic inclusions 4, 5

Diagnosis and Diagnostic Criteria

• The diagnosis of MSA may be challenging and is usually made at a tertiary care center 2
• The second consensus criteria for MSA have suboptimal diagnostic accuracy, particularly in early disease stages 5
• Red flags highly specific for MSA may provide clues for a correct diagnosis 5

Treatment and Management

• There is currently no cure for MSA, and treatment focuses on the most problematic symptoms experienced by the patient 2
• Symptomatic management remains disappointing, and no curative treatment is yet available 3
• Autonomic and urogenital features of MSA can be treated effectively in many instances 6
• A team approach involving primary care providers and subspecialists is recommended for the management of MSA patients 2

Pathogenesis and Future Perspectives

• The underlying pathogenesis of MSA is still not well understood 4
• Recent experimental evidence has confirmed the key role of alpha-synuclein aggregation in the pathogenesis of MSA 3
• Future approaches for the management of MSA include the development of transgenic and toxic animal models to assess candidate drugs 3
• Standardization of diagnosis criteria and assessment procedures will allow large multicentre clinical trials to be conducted 3