http://www.parkinson.org/atrophy.htm
Parkinson's Report
National Parkinson's Foundation, Inc.
VOLUME XIX - ISSUE 2 / Spring 1998
Multiple System Atrophy
By members of the National Parkinson Foundation Center of Excellence at
Vanderbilt University, including David A. Robertson, Director, Nathan S.
Blaser
Shy-Drager Research Laboratories; Thomas L. Davis, 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)
"There can be no happiness if the things we believe in are different
from the things we do." - Author Unknown
