C h a p t e r 3 6
Disorders of Neuromuscular Function
901
Treatment.
The approach to treatment of Parkinson
disease must be highly individualized. It includes non-
pharmacologic, pharmacologic, and, when indicated,
surgical methods.
33,34,40
Nonpharmacologic interventions
offer group support, education, daily exercise, and ade-
quate nutrition. Botulinum toxin injections may be used in
the treatment of dystonias such as eyelid spasm and limb
dystonias that frequently are associated with Parkinson
disease. Persons with parkinsonism other than idiopathic
Parkinson disease usually do not respond significantly to
medications developed for Parkinson disease.
Pharmacologic treatment usually is determined by
the severity of symptoms. Antiparkinson drugs act by
increasing the functional ability of the underactive dopa-
minergic system, or by reducing the excessive influence
of excitatory cholinergic neurons. Drugs that improve
the function of the dopaminergic system include those
that increase dopamine levels (levodopa), stimulate
dopamine receptors (dopamine receptor agonists), or
retard the breakdown of dopamine (monoamine oxi-
dase-B inhibitors).
40
Levodopa, a dopamine agonist, is administered
with carbidopa, which inhibits its peripheral metabo-
lism, allowing therapeutic concentrations of the drug to
enter the brain without disabling adverse effects. A later
adverse effect of levodopa treatment is the so-called
on–off phenomenon,
in which frequent, abrupt, and
unpredictable fluctuations in motor performance occur
during the day. These fluctuations include “on” peri-
ods without dyskinesia, “on” periods with dyskinesia,
and periods of bradykinesia (the “off” response). Some
fluctuations reflect the timing of drug administration, in
which case the “on” response coincides with peak drug
levels and the “off” response with low drug levels.
Dopamine agonists such as pramipexole (Minaprex)
and ropinirole (Requip) directly stimulate dopamine
receptors. Rotigotine is a dopamine agonist that is sup-
plied in a transdermal system. The dopamine agonists
can be used as initial or adjunctive therapy in Parkinson
disease and can be given in combination with carbidopa/
levodopa. Rotigotine is only approved by the U.S. Food
and Drug Administration (FDA) for initial treatment of
Parkinson disease.
Amantidine, an antiviral agent, was found by chance
to have antiparkinson properities. It is thought to aug-
ment release of dopamine from the remaining intact
dopaminergic terminals in the nigrostriatal pathway of
persons with Parkinson disease. It is used to treat per-
sons with mild symptoms but no disability.
Several medications are used for adjuvant therapy
as the initial therapy becomes less effective in control-
ling motor complications. As the therapy less effec-
tively controls the symptoms, there is less “on time”
(when the symptoms are controlled) and more “off
time”. Apomorphine is a dopamine agonist that can be
given intravenously. It is often used as a rescue medica-
tion in patients experiencing sudden “off” periods or
delayed “on” periods. Monamine oxidase-B inhibitors,
such as selegiline and rasagiline, hinder the metabolic
breakdown of dopamine. Selegiline and rasagiline may
be used as adjunctive treatment to reduce mild on–off
fluctuations in the responsiveness of persons who are
receiving levodopa.
Because dopamine transmission is disrupted in
Parkinson disease, there is a preponderance of cholin-
ergic activity. Anticholinergic drugs (e.g., trihexyphe-
nidyl, benztropine) are thought to restore a “balance”
between reduced dopamine and uninhibited cholinergic
neurons in the striatum. They are more useful in alleviat-
ing tremor and rigidity than bradykinesia. The anticho-
linergic drugs lessen the tremors and rigidity and afford
some improvement of function. However, their potency
seems to decrease over time, and increasing the dosage
merely increases side effects such as blurred vision, dry
mouth, bowel and bladder problems, cognitive dysfunc-
tion, and hallucinations.
Deep brain stimulation, which involves the surgical
implantation of electrodes into the subthalamic nuclei
or the pars interna of the globus pallidus, is an option
for many persons who develop symptoms despite opti-
mal medical therapy.
40,41
The electrodes are connected
to a surgically implanted impulse generator that delivers
electrical simulation to block the abnormal nerve activ-
ity that causes tremor and abnormal motor activity in
Parkinson disease. The system allows the stimulation to
be programmed to control the individual person’s symp-
toms, and the stimulation parameters can be changed
over time as the disease progresses. Deep brain stimu-
lation is used for persons with Parkinson disease who
respond to levodopa but experience side effects associ-
ated with it (e.g., motor fluctuation or dyskinesia). It
is not a cure but serves to increase the duration of the
“on” periods, allows for a reduction in medication dos-
ages (in subthalamic nuclei stimulation), and improves
function. Of note, other movement disorders can be
treated by placing electrodes in different target sites
(e.g., thalamus for tremor and globus pallidus internus
for dystonia).
SUMMARY CONCEPTS
■■
Both uncoordinated and abnormal muscle
movements can result from disorders of the
cerebellum and basal ganglia.
■■
The functions of the cerebellum, which
are especially vital during rapid muscular
movements, use afferent input from various
sources, including stretch receptors,
proprioceptors, tactile receptors in the skin,
visual input, and the vestibular system. Signs
of cerebellar disorders include dystaxia, ataxia,
tremor, and dysarthria.
■■
The basal ganglia organize basic movement
patterns into more complex patterns and release
them when commanded by the motor cortex,
contributing gracefulness to cortically initiated
(continued)
