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Multiple System Atrophy


Multiple System Atrophy (MSA) is a rare and progressive neurodegenerative disorder that predominantly affects the central nervous system. Characterised by a combination of parkinsonism, autonomic dysfunction, and cerebellar ataxia, MSA results from the degeneration of neurons in various brain regions, including the basal ganglia, inferior olivary nucleus, and cerebellum. The condition manifests typically between the ages of 50 and 60 and has a life expectancy of 6-12 years post-onset.

Alpha-synuclein immunohistochemistry of the brain showing many glial inclusion bodies
Alpha-synuclein immunohistochemistry of the brain showing many glial inclusion bodies

Signs and Symptoms

MSA presents with a variety of symptoms, which can be grouped into autonomic, motor, and cerebellar dysfunctions. Autonomic dysfunction is a hallmark and includes symptoms such as orthostatic hypotension, impotence, loss of sweating, dry mouth, urinary retention, and incontinence. Vocal cord palsy is also a significant and sometimes initial symptom.

Motor symptoms include parkinsonism, characterised by tremors, muscle rigidity, slow movements, and postural instability. These symptoms can be categorised into two subtypes: MSA-P (predominant parkinsonism) and MSA-C (predominant cerebellar ataxia). Cerebellar ataxia results in poor coordination and unsteady walking.

Initial signs often include an "akinetic-rigid syndrome," balance issues, and genito-urinary symptoms. As the disease progresses, patients may experience severe autonomic dysfunction, parkinsonism, or cerebellar dysfunction, along with secondary complications such as cognitive impairment and sleep disturbances.


Clinical Diagnosis

Clinical diagnostic criteria for MSA, updated in 2022, emphasise the presence of autonomic dysfunction and at least one motor symptom. Diagnostic methods include MRI and CT scans that may reveal atrophy in the cerebellum and pons. However, these changes can be subtle and require experienced examiners to identify.

Pathologic Diagnosis

A definitive diagnosis of MSA can only be made post-mortem through histological examination, identifying abundant glial cytoplasmic inclusions (GCIs) in the central nervous system. These inclusions contain alpha-synuclein, a protein whose abnormal accumulation also characterises other synucleinopathies like Parkinson's disease.


MSA involves cell loss and gliosis in the central nervous system, leading to the formation of glial scars. The presence of Papp-Lantos bodies, which contain alpha-synuclein, is a defining feature. Unlike other synucleinopathies, MSA primarily affects oligodendrocytes, with limited neuronal involvement. Recent studies have shown that neuronal alpha-synuclein pathology is more abundant than previously thought.


Drug Therapy

Levodopa (L-Dopa), commonly used for Parkinson's disease, provides limited and transient relief for MSA patients. Other drugs like fludrocortisone and midodrine are used to manage orthostatic hypotension. Riluzole has been found ineffective in treating MSA.


Rehabilitation is very important for managing MSA. Physiotherapists help maintain mobility and prevent contractures, while speech therapists address dysarthria and dysphagia. Early intervention for swallowing difficulties is essential to discuss tube feeding options as the disease progresses.

Supportive Care

Social workers and occupational therapists play a essential role in providing equipment, home adaptations, and support services for both patients and caregivers. Hospice and homecare services become increasingly important as disability progresses.


The prognosis for MSA is poor, with an average lifespan of 6-10 years post-onset. Patients often require wheelchairs within five years and rarely survive beyond 12 years. The disease progresses without remission, and those with severe autonomic dysfunction or presenting at an older age have a poorer prognosis.

Complications such as infections from urinary catheters, feeding tubes, and aspiration pneumonia are common causes of death. Cachexia, or wasting syndrome, also contributes to mortality.


MSA affects approximately 5 per 100,000 people, with a slight male predominance. The condition is often misdiagnosed as Parkinson's disease, suggesting a higher actual incidence. Most cases present in individuals aged 50-60 years.


Emerging research indicates that mesenchymal stem cell therapy may delay the progression of neurological deficits in MSA-C. However, more studies are needed to confirm these findings and develop effective treatments.

Notable Cases

  • Nikolai Andrianov: Soviet gymnast with 15 Olympic medals.
  • Johnny Cash: Diagnosed with Shy–Drager syndrome in 1997.
  • Kenneth More: British actor originally diagnosed with Parkinson's disease.
  • Kerry Simon: Chef who died from complications of MSA.

Self-assessment MCQs (single best answer)

Which of the following is NOT a hallmark symptom of Multiple System Atrophy (MSA)?

MSA is characterised by the degeneration of neurons in various brain regions. Which of the following regions is NOT primarily affected?

Which protein's abnormal accumulation is a defining feature of Multiple System Atrophy?

What is the average life expectancy for a patient diagnosed with MSA post-onset?

Which diagnostic method is definitive for confirming MSA?

Which symptom is often an initial sign of MSA?

What type of drug is commonly used for managing parkinsonism symptoms in MSA patients, although with limited effectiveness?

Which of the following is a common complication and cause of death in MSA patients?

What proportion of the population is affected by Multiple System Atrophy?

Which notable figure was diagnosed with Shy–Drager syndrome, a form of MSA?


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