Multiple System Atrophy Article

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http://www.parkinson.org/atrophy.htm

Multiple System Atrophy

By members of the National Parkinson Foundation Center of

Excellence at Vanderbilt

University, including A. on, Director, S.

Blaser Shy-Drager Research

Laboratories; L. , Director, Movement Disorder Clinic;

and Ariel Y. Deutch,

Director, NPF Center of Excellence

Although the cause of idiopathic Parkinson’s disease is unknown,

Parkinson’s disease is

probably the best characterized of the neurodegenerative disorders.

The loss of dopamine in

the striatum is the major contributor to the disorder. However,

there are several other

neurodegenerative disorders involving several different systems in

the brain, in which striatal

dopamine loss is also found.

Among these other neurodegenerative disorders is multiple system

atrophy (MSA), in which

degeneration in diverse brain regions leads to problems in the

control of movement, balance,

blood pressure, and sexual and urinary tract function. MSA is often

accompanied by some

striatal dopamine loss and in certain patients typical parkinsonian

symptoms are either the first

noted or the most prominent.

A number of areas of the brain are involved by MSA. This has led to

different varieties of

MSA receiving different names, depending on which area of the brain

has predominant

involvement. When MSA begins with imbalance, incoordination, and

difficulties in speaking

(dysarthria), it is often called olivopontocerebellar atrophy; as

the name suggests, this form of

MSA is marked by degeneration in the cerebellum, a structure

involved in balance and learned

motor tasks. When a patient initially has rigidity (stiffness) and

slowness in initiating

movements (bradykinesia) that is out of proportion to tremor, this

MSA form has been called

striatonigral degeneration, involving communication between nerve

cells in the striatum and

midbrain. In patients in whom changes in autonomic function

dominates the initial

presentation, particularly changes in blood pressure regulation,

the MSA form is often called

Shy-Drager syndrome.

Between 25,000 and 100,000 American have multiple system atrophy.

However, many will

not receive the correct diagnosis during their lifetime. This is

due to the difficulty in

differentiating MSA from other disorders (including relatively

common degenerative disorders

such as Parkinson’s disease and more rare ones such as pure

autonomic failure). MSA usually

occurs after age 50, with a slightly higher incidence in males.

Patients usually have autonomic

nervous system dysfunction first. Genitourinary dysfunction

(difficulty with urination) is the

most frequent initial complain in women, while impotence is the

most frequent initial complaint

in men. Orthostatic hypotension (a large drop in blood pressure

upon standing) is common and

may cause dizziness, dimming of vision, head or neck pain, yawning,

temporary confusion,

slurred speech, and if the hypotension is severe, the patient may

" faint " upon arising from a

recumbent position. In spite of low blood pressure while standing,

it is common for MSA

patients to have high blood pressure when lying down. A fall in

blood pressure following meals

or in hot weather or following infection is quite common.

When MSA begins with non-autonomic features, imbalance is the most

common feature. This

difficulty in maintaining balance may be due to either cerebellar

or Parkinsonian abnormalities.

Some patients complain of stiffness, clumsiness, or a change in

handwriting at the onset of

MSA. The concurrent involvement in MSA of multiple brain systems

subserving movement,

including the striatum, cerebellum, and cortex, leads to the

movement disorder as often being

the most profound disability. Hoarseness or even vocal paralysis

are relatively common, as are

sleep disturbances, including snoring and sleep apnea. The ability

to swallow foods and liquids

may be impaired.

The initial diagnosis of MSA is usually made by carefully

interviewing the patient and

performing a physical examination. However, more testing is often

needed to confirm the

diagnosis. Among the tests that are helpful in determining the

presence of MSA are several

types of brain imaging including computerized tomography (CT)

scans, magnetic resonance

imaging (MRI), and positron emission tomography (PET).

Pharmacological challenge tests

(administering certain drugs in the presence of various types of

movements of the patient) may

also be of help. In those patients with typical parkinsonian signs,

an incomplete and relatively

poor response to dopamine replacement therapy (such as l-dopa

[sinemet]) may be a clue that

MSA is present.

The characteristic involvement of multiple brain systems is a

defining feature of MSA, and one

that on autopsy confirms the diagnosis. Recently, several groups

have reported the presence of

unusual inclusions in certain types of brain cells. These glial

cytoplasmic inclusions are, as the

name indicates, typically found in glial cells, which are the

structural and metabolic support

elements of the brain but are not neurons (nerve cells). Glial

cells are central to maintaining the

correct balance of ions in the brain, without which neurons cannot

survive. Moreover, glial

cells express certain proteins that accumulate and thereby limit

extracellular excitatory amino

acids that can be toxic to neurons. These functions of glial cells,

coupled with the presence of

glial cytoplasmic inclusions in MSA but not Parkinson’s disease,

have sparked considerable

research interest. It is noteworthy that a different type of

intracellular inclusion in nerve cells,

the Lewy body, is present in Parkinson’s disease but not MSA.

In MSA, there is loss of function in the two divisions of the

peripheral nervous system: the

sympathetic and parasympathetic nervous systems. Although the

autonomic nerves themselves

are largely intact, the brain loses its capacity to properly engage

them to control the autonomic

function. Consistent with the involvement of many brain regions in

MSA, the concentrations of

many neurotransmitters in the brain are reduced in MSA.

As with Parkinson’s disease, the cause of MSA remains unknown.

Antibodies in the spinal

fluid of patients with MSA have been shown to react with a specific

area in an experimental

animal brain, raising the possibility that MSA may be related to an

abnormality of the immune

system. It is also possible that MSA is due to abnormal folding of

some unknown protein. At

this time, however, these observations require independent

confirmation in large groups of

patients, and the relationship of such changes to specific symptoms

in MSA remains unclear.

What is clear is that there is a compelling need for research into

the causes, and hence

treatment and cure, of MSA and Parkinson’s disease.

MSA is a rare and sporadic disorder and available evidence does not

support a hereditary

component to the disorder. Among more than 400 patients evaluated

at Vanderbilt University

Medical Center’s Autonomic Dysfunction Center during the past 20

years, not one had a

family member with MSA, although a number of them had family

members with Parkinson’s

or Alzheimer’s disease. While it is possible that a few of these

family members diagnosed with

Parkinson’s or Alzheimer’s disease might have actually had MSA,

available data strongly

suggests that MSA is not inherited. In Parkinson’s disease there is

a similar but not identical

situation, with hereditary forms of the disease representing only a

small minority of the

patients; even in these patients, the disease process differs

somewhat from idiopathic

Parkinson’s disease. There is no evidence that MSA is contagious;

we have never observed

people in the same house who developed the disease.

Given the relative rareness of MSA and the frequent misdiagnosis of

the disorder, it is not

surprising that there is a paucity of careful epidemiological

investigations of MSA that allow

one to identify predisposing environmental factors. Although one

report raised the possibility of

a small effect of exposure to environmental toxins and another

report suggested a slight

correlation with prior head injury, these claims have not yet been

supported by other studies.

In particular, MSA does not appear to be related to or caused by

prior alcohol or drug abuse,

poor nutrition, or other disease process earlier in life.

MSA may progress rapidly. Patients survive an average of nine years

following onset of illness;

some patients live as much as twice this long. Current treatment of

MSA is symptomatic. The

most valuable agents to increase blood pressure are fludrocortisone

and midodrine. In addition,

most patients with MSA derive some benefit from typical

antiparkinsonian medications such as

levodopa (Sinemet), dopaminergic agonists (pergolide and

bromocriptine), and anticholinergic

drugs.

In summary, MSA is a severe neurodegenerative disorder of unknown

cause. There is

currently no cure for MSA, nor is there any therapy available that

stops or slows the

progression of the disease. At this time, treatment is aimed at

treating problems as they arise,

and thus requires careful monitoring of the patient by a skilled

and experienced clinician with

expertise in MSA.

The lack of specific treatments to cure or slow the progression of

MSA is disheartening to

patients and their loved ones and caregivers. However, exensive

research efforts aimed at

advancing our understanding of MSA, Parkinson’s disease and other

neurodegenerative

disorders are in place, and we have enjoyed a period of very rapid

advances in understanding

of the pathophysiology of neurodegenerative disorders. We can

expect such advances to

culminate in a better understanding and treatment for MSA and

Parkinson’s disease over the

next decade.

Multiple System Atrophy

Olivopontocerebellar Atrophy

Striatonigral Degeneration

Shy-Drager Syndrome

Symptoms of MSA

difficulty with urination

impotence

orthostatic hypotension

gastric fullness

loss of sweating

frequent nighttime urination

imbalance

incoordination

hoarseness/snoring

muscle weakness

Parkinson’s Disease vs. Multiple System Atrophy: Observations

Suggestive of MSA

Poor response to Sinemet

Low blood pressure on standing

Difficulty with urination

Use of a wheelchair

Loud snoring or loud breathing

Frequent nighttime urination

Treatment of MSA

Fludrocortisone (blood pressure)

Midodrine (blood pressure)

Sinemet (movement disorder)

Dopaminergic Agonists (movement disorder)

Anticholinergics (movement disorder)

Erythropoietin (anemia)