Wisdom of Life

Understanding MSA

Multiple system atrophy (MSA) is a progressive neurological disorder that affects adult men and women. It is caused by degeneration or atrophy of nerve cells in several (or multiple) areas of the brain which can result in problems with movement, balance and automatic functions of the body such as bladder and blood pressure control. The Olufunmilayo Khafasat Foundation is a Nigerian based support and information service for people with multiple system atrophy, their families and carers. It also funds research into the treatment and causes of MSA.

The cause of MSA is unknown and no specific risk factors have been identified. Around 55% of cases occur in men, with typical age of onset in the late 50s to early 60s.

The overall prevalence of MSA is estimated at 4.6 cases per 100,000 people. This disease is more common in men than in women, with studies showing ratios ranging from between 1.4:1 to ratios as high as 1.9:1.

MSA is characterized by a combination of the following, which can be present in any combination:

  • Autonomic dysfunction
  • Parkinsonism (muscle rigidity +/ tremor and slow movement)
  • Ataxia (Poor coordination / unsteady walking)

MSA usually progresses more quickly than Parkinson’s disease. There is no remission from the disease. The average remaining lifespan after the onset of symptoms in patients with MSA is 7.9 years.

Almost 80% of patients are disabled within 5 years of onset of the motor symptoms, and only 20% survive past 12 years. Rate of progression differs in every case and speed of decline may vary widely in individual patients.

’Sullivan and colleagues (2008) identified early autonomic dysfunction to be the most important early clinical prognostic feature regarding survival in MSA. Patients with concomitant motor and autonomic dysfunction within 3 years of symptom onset had shorter survival duration, in addition to becoming wheelchair dependent and bed-ridden at an earlier stage than those who developed these symptoms after 3 years from symptom onset. Their study also showed that when patients with early autonomic dysfunction develop frequent falling, or wheelchair dependence, or severe dysphagia, or require residential care, there is a shorter interval from this point to death.

Diagnosis

Diagnosis of MSA can be challenging because there is no test that can definitively make or confirm the diagnosis in a living patient. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson’s disease, making the diagnosis more difficult.

A definitive diagnosis can only be made pathologically on finding abundant glial cytoplasmic inclusions in the central nervous system.

Histopathology

Multiple system atrophy can be explained as cell loss and gliosis or a proliferation of astrocytes in damaged areas of the central nervous system. This damage forms a scar which is then termed a glial scar. Currently, a confirmed diagnosis of MSA can only be made post-mortem as glial cytoplasmic inclusion bodies are visible. When brain tissue of a person with MSA is examined under a microscope, these glial structures are visible, confirming the diagnosis. The presence of these inclusions (also known as Papp-Lantos bodies) in the movement, balance and automatic control centres of the brain are the defining histopathologic hallmark of MSA. Recent studies have shown that major filamentous component of glial and neuronal cytoplasmic inclusions are alpha-synuclein. Mutations in this substance may play a role in the disease. Tau proteins have been found in some GCIs

Symptoms

MSA can cause a wide range of symptoms, including:

  • Stiffness or rigidity
  • Freezing or slowed movements
  • Postural instability; loss of balance; incoordination
  • Tremor
  • Orthostatic hypotension
  • Male impotence
  • Urinary incontinence
  • Constipation
  • Speech and swallowing difficulties
  • Sleep disorder
  • Hyperreflexia

Terminology

Many terms have historically been used to refer to this disorder, based on the predominant systems presented. These include Olivopontocerebellar atrophy (OPCA), Shy-Drager syndrome (SDS), and Striatonigral degeneration (SND), which were once considered to be separate disorders

These terms and their distinctions have been dropped in recent (1996 onwards) medical usage and replaced with MSA and its subtypes, but are helpful to understanding the older literature about this disease:

Historical Name
Characteristics
Abbreviation and Modern Name

Striatonigral degeneration

Predominating Parkinson's-like symptoms

MSA-P, "p" = parkinsonian subtype

Sporadic Olivopontocerebellar atrophy (OPCA)

MSA-C, "c" = cerebellar dysfunction subtype

Shy-Drager syndrome

Characterized by Parkinsonism plus a more pronounced failure of the autonomic nervous system.

MSA-A, "a" = autonomic dysfunction subtype. (Not specified in 2007)

 

The current terminology and diagnostic criteria for the disease were established at a 2007 conference of experts on the disease and set forth in the "Second consensus statement on the diagnosis of multiple system atrophy.

The Second Consensus Statement defines two categories of MSA, based on the predominant symptoms of the disease at the time of evaluation. These are:

  • MSA with predominant Parkinsonism (MSA-P) MSA-P is defined as MSA where extrapyramidal features predominate. The term striatonigral degeneration, parkinsonian variant, is sometimes used for this category of MSA.
  • MSA with cerebellar features (MSA-C). MSA-C is defined as MSA where cerebellar ataxia predominates. It is sometimes termed sporadic olivopontocerebellar atrophy.