A triad of coexisting neurodegenerative disorders that manifest collective symptoms of autonomic, ataxic (cerebellar), and extrapyramidal (parkinsonian) dysfunctions. The predominant set of symptoms determines the commonly assigned name for the disorder, although the overall syndrome is more appropriately designated as multiple system atrophy (MSA) type A (autonomic), type C (cerebellar), or type P (parkinsonian). Symptoms typically begin when a person is in the mid-40s to mid-50s; When parkinsonism is the predominant set of symptoms, it is not unusual for clinicians to misdi-agnose the condition as Parkinson’s disease; ataxic (cerebellar) and autonomic features may not become apparent until years later in some people. Some experts classify MSA as one of the parkin-son’s plus syndromes on the premise that its core element is Parkinson’s disease with additional overlying dysfunctions.
Scientists estimate that about 10 percent of people who are incorrectly diagnosed with Parkinson’s have MSA. However, only at autopsy after death can the diagnosis be certain for either MSA or Parkinson’s. The main clue during the course of the disease that a person has MSA instead of Parkinson’s is rapid and significant deterioration; typically MSA results in death within seven to 10 years of diagnosis. The causes of MSA are unknown but are likely as multiple and intertwined as its symptoms. There are few effective treatments after the early stage of MSA. MSA is a devastating diagnosis for the person who has the disorder as well as for loved ones.
Ataxic Dysfunction (MSA-C): Olivopontocerebellar Atrophy (OPCA)
Olivopontocerebellar atrophy (OPCA) is the progressive deterioration of key structures of the medulla called the olives (because they physically resemble olives); of the cerebellum, the part of the brain that coordinates muscle activity and movement; and of the pons, a structure of the brain-stem. With the physical loss of cells and tissues there occurs a corresponding loss of function that is manifested as ataxia (lack of balance and coordination). Intentional or kinetic tremor (a tremor that is present during intentional actions such as reaching for an object) also often occurs. Other symptoms of cerebellar dysfunction are similar to the symptoms of Parkinson’s, including dyskinesia (involuntary movements) and dystonia (severe rigidity with muscles often “frozen” in awkward positions). dysarthria (difficulty in forming words) and choreic movements also are part of the OPCA component of MSA.
Autonomic Dysfunction (MSA-A): Shy-Drager Syndrome
Disturbances of involuntary functions are the hallmark of the Shy-Drager syndrome component of MSA. These include urinary incontinence or retention, intestinal problems such as diarrhea or constipation, sexual dysfunction (particularly erectile dysfunction), changes in sensory perceptions, orthostatic hypotension (drop in blood pressure on changing position), and irregularities in heartbeat. Medications appropriate for each of these dysfunctions often can relieve symptoms in the early stages of MSA but may not be very effective as the degeneration progresses.
Extrapyramidal Dysfunction (MSA-P): Striatonigral Degeneration
MSA’s extrapyramidal symptoms are much the same as those of Parkinson’s disease and often include Parkinson’s four classic or cardinal symptoms: resting tremor, bradykinesia (slowed movement), rigidity (muscle stiffness and resistance to movement), and postural instability. This similarity occurs because the same kind of damage develops in the striatum, substantia nigra, and other structures of the basal ganglia that are key to movement. dopaminergic neurons in these parts of the brain rapidly die and the brain’s supply of dopamine diminishes. Notably tremor is often less prominent in MSA-P than in Parkinson’s, and postural instability both presents much earlier in the disease course and is more severe than in Parkinson’s. The olivopontocerebellar atrophy aspect of MSA involves significant atrophy (shrinking) of the cerebellum, another part of the brain that is important to motor functions, particularly coordination. Often this atrophy appears in imaging studies such as magnetic resonance imaging (MRI) or Computed tomography (ct) scan, or in functional imaging studies such as positron emission tomography (PET) and single photon emission computed tomography (SPECT).
In MSA, neurons contain substances called inclusions, abnormal but indistinct deposits throughout the cell’s cytoplasm that can be detected at autopsy. As are lewy bodies, the characteristic protein deposits that infiltrate brain neurons in Parkinson’s disease, MSA inclusions are primarily alpha-synuclein. However, these inclusions are distinct from Lewy bodies in structure and composition, microscopically and biochemically. As well, MSA inclusions also infiltrate brain cells called glial cells, whose function is to support and protect neurons. Inclusion infiltration is fairly widespread throughout the brain.
The neuromuscular symptoms of MSA progress more rapidly than in Parkinson’s, often leading to debilitation within a few years of diagnosis when extrapyramidal dysfunction is the predominant cluster of symptoms. Bradykinesia, dyskinesia, dystonia, and akinesia (lack of movement) typically are more pronounced than tremors. When the person with MSA does have tremors, typically myoclonus is also present. Cerebellar atrophy causes additional neuromuscular symptoms such as ataxia (lack of muscle coordination and balance), which affects postural stability, gait, and
Differential Diagnosis and Treatment
Each of the conditions that MSA comprises has distinct anatomical characteristics that often can be visualized through imaging studies as well as distinct typical functional characteristics on functional imaging. These characteristics can help to differentiate MSA from Parkinson’s disease. A test of lev-odopa therapy also can provide clinical clues, as levodopa is not effective in about two thirds of people with MSA and is effective only for a short time in others.
There really are few therapeutic options for MSA at present. Making an accurate diagnosis nonetheless is important so people with either diagnosis can make informed and appropriate decisions. If the diagnosis is Parkinson’s disease, immediate and aggressive treatment with anti-parkinson’s medications can improve quality of life and delay debilitation. In MSA’s early stages, anti-Parkinson’s medications sometimes control some motor symptoms, but not for long (generally no more than two or three years) because of MSA’s swift progression, and not completely. Also because symptoms progress rapidly, relief through surgical therapies such as deep brain stimulation (DBS) or pallidotomy is so minimal that the benefits of surgery do not outweigh the risks; surgery is seldom considered an option for MSA. When anti-Parkinson’s medications fail, treatment for neuromuscular symptoms is primarily supportive. Other medications can provide relief for symptoms of the Shy-Drager syndrome component of the triad, such as orthostatic hypotension (fludrocorti-sone, minodrine) and urinary incontinence (tolterodine, oxybutynin).