C h a p t e r 3 6
Disorders of Neuromuscular Function
899
Parkinson Disease
Parkinson disease is a progressive degenerative disor-
der of basal ganglia function that results in variable
combinations of tremor, rigidity, and bradykinesia.
33,34
Parkinson disease is the second most common neuro-
degenerative disease after Alzheimer disease. It usually
begins after 50 years of age, with the prevalence increas-
ing to 4% to 5% in those older than 85 years of age.
33
The clinical syndrome arising from the degenerative
changes in basal ganglia function often is referred to
as
parkinsonism.
Parkinson disease, the most common
form of parkinsonism, is named after James Parkinson,
a British physician who first described the disease in a
paper he published in 1817 on the “shaking palsy.”
35
In
Parkinson disease, also known as
idiopathic parkinson-
ism,
dopamine depletion results from degeneration of the
dopamine nigrostriatal system. Parkinsonism can also
develop as a postencephalitic syndrome, as a side effect
of therapy with antipsychotic drugs that block dopamine
receptors, as a toxic reaction to a chemical agent, or as an
outcome of severe carbon monoxide poisoning.
36
Drug-
induced parkinsonism can follow the administration of
antipsychotic drugs in high doses (e.g., phenothiazines,
butyrophenones). These drugs block dopamine receptors
and dopamine output by the cells of the substantia nigra.
Symptoms of parkinsonism also may accompany con-
ditions such as cerebral vascular disease, brain tumors,
repeated head trauma, or degenerative neurologic dis-
eases that structurally damage the nigrostriatal pathway.
The primary brain abnormality found in persons
with Parkinson disease is degeneration of the nigros-
triatal pathway, with subsequent reduction in striatal
concentrations of dopamine. Other brain areas are
affected to a lesser extent.
37,38
Although the cause of
Parkinson disease is still unknown, it is widely believed
that most cases are caused by an interaction of envi-
ronmental and genetic factors. Over the past several
decades, several pathologic processes (e.g., oxidative
stress, apoptosis, and mitochondrial disorders) that
might lead to degeneration have been identified.
There is increasing evidence that the development of
Parkinson disease may be related to oxidative metabo-
lites and the inability of neurons to render these prod-
ucts harmless. Of interest in terms of research was the
development of Parkinson disease in several persons
who had attempted to make a narcotic drug and instead
synthesized a compound called
MPTP (1-methyl-
phenyl-2,3,6-tetrahydropyridine)
.
37,38
This compound
selectively destroys the dopaminergic neurons of the
substantia nigra. This incident prompted investigations
into the role of toxins that are produced by the body
as a part of metabolic processes and those that enter
the body from outside sources in the pathogenesis of
Parkinson disease. One theory is that the auto-oxida-
tion of catecholamines, such as dopamine, may injure
neurons in the substantia nigra. MPTP is an inhibitor of
the mitochondrial electron transport system that func-
tions in the inactivation of these metabolites, suggesting
that it may produce Parkinson disease in a manner simi-
lar to that of the naturally occurring disease.
The recent discovery of inherited forms of Parkinson
disease suggests that genetic factors may also play a
role in the pathogenesis of early-onset Parkinson dis-
ease.
37–39
The first genetic mutation associated with
TABLE 36-1
Characteristics of Basal Ganglia–Associated Movement Disorders
Movement Disorder Characteristics
Tremor
Involuntary, oscillating contractions of opposing muscle groups around a joint
Usually fairly uniform in frequency and amplitude
Can occur as resting tremors and postural tremors, which occur when the part is maintained in a
stable position
Hypokinetic disorders
Slowness in initiating movement, and reduced range and force of the movement (bradykinesia)
Chorea
Irregular wriggling and writhing movements
Accentuated by movement and by environmental stimulation; they often interfere with normal
movement patterns
May be grimacing movements of the face, raising the eyebrows, rolling of the eyes, and curling,
protrusion, and withdrawal of the tongue
In the limbs, the movements largely are distal; there may be piano playing–type movements with
alternating extension and flexion of the fingers
Athetosis
Continuous, wormlike, twisting and turning motions of the joints of a limb or the body
Ballismus
Violent, sweeping, flinging motions, especially of the limbs on one side of the body (hemiballismus)
Dystonia
Abnormal maintenance of a posture resulting from a twisting, turning movement of the limbs, neck,
or trunk
Often the result of simultaneous contraction of agonist and antagonist muscles
Can result in grotesque and twisted postures
Dyskinesias
Bizarre wriggling and writhing movements
Frequently involve the face, mouth, jaw, and tongue, causing grimacing, pursing of the lips, or
protrusion of the tongue
Limbs affected less often
Tardive dyskinesia is an untoward reaction that can develop with long-term use of some antipsychotic
medications
