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Nervous System
the disease.
10,11
A specific molecular genetic diagnosis
is possible by demonstrating the defective dystrophin
gene in a blood sample. Muscle biopsy, which shows
a mixture of muscle cell degeneration and regeneration
and reveals fat and scar tissue replacement, may be done
to confirm the diagnosis. The same methods of genetic
testing may be used on blood samples to establish car-
rier status in female relatives at risk, such as sisters and
cousins. Prenatal diagnosis is possible as early as 12
weeks’ gestation by sampling chorionic villi for DNA
analysis
10
(see Chapter 6). Echocardiography, electro-
cardiography, and chest radiography are used to assess
cardiac function.
Management of the disease is directed toward main-
taining ambulation and preventing deformities. Passive
stretching, correct or counterposturing, and splints help
to prevent deformities. Precautions should be taken to
avoid respiratory infections.
Glucocorticoids are the only medication currently
available to slow the decline in muscle strength and
function in DMD.
10,11
Steroids decrease inflammation,
prevent fibrosis, and improve muscle regeneration.
Disorders of the Neuromuscular
Junction
The neuromuscular junction serves as a synapse
between a motor neuron and a skeletal muscle fiber.
3
It
consists of the axon terminals of a motor neuron and
a specialized region of the muscle membrane called the
endplate.
The transmission of impulses at the neuro-
muscular junction is mediated by the release of the neu-
rotransmitter
acetylcholine
from the axon terminals.
Acetylcholine binds to specific receptors in the end-
plate region of the muscle fiber surface to cause muscle
contraction (Fig. 36-6A). Acetylcholine is active in the
neuromuscular junction only for a brief period, during
which an action potential is generated in the innervated
muscle cell. Some of the transmitter diffuses out of
the synapse, and the remaining transmitter is rapidly
inactivated by an enzyme called
acetylcholinesterase
(see Chapter 34, Fig. 34-25A). The rapid inactivation of
acetylcholine allows repeated muscle contractions and
gradations of contractile force.
Drug- andToxin-Induced Disorders
A number of drugs and agents can alter neuromus-
cular function by changing the release, inactivation,
or receptor binding of acetylcholine. Curare acts on
the postjunctional membrane of the motor endplate
to prevent the depolarizing effect of the neurotrans-
mitter. Neuromuscular transmission is blocked by
curare-type drugs during many types of surgical pro-
cedures to facilitate relaxation of involved muscula-
ture. Drugs such as physostigmine and neostigmine
inhibit the action of acetylcholinesterase and allow
acetylcholine released from the motor neuron to
accumulate. These drugs are used in the treatment of
myasthenia gravis.
Neurotoxins fromthe botulismorganism(
Clostridium
botulinum
) produce paralysis by blocking acetylcholine
release.
3
Clostridia are anaerobic, gram-positive, spore-
forming bacilli found worldwide in soils, marine and
fresh water sediments, and the intestines of many ani-
mals. Classic food-borne botulism occurs through inges-
tion of soil-grown foods that are not properly cooked or
preserved.
12
Canned vegetables, items preserved in gar-
lic oil, and soups are usually the cause of sporadic out-
breaks. Wound botulism occurs through colonization of
wounds with
C. botulinum.
Pharmacologic preparations of the botulinum toxin
(botulinum type A toxin [Botox] and botulinum type B
toxin [Myobloc]) have become available for use in treat-
ing eyelid and eye movement disorders such as blepha-
rospasm and strabismus.
12,13
These agents also are used
for treatment of spasmodic torticollis, spasmodic dys-
phonias (laryngeal dystonia), and other dystonias. The
drug is injected into the target muscle using the elec-
trical activity recorded from the tip of a special elec-
tromyographic injection needle to guide the injection.
The treatment is not permanent and usually needs to be
repeated approximately every 3 months.
Normal
Myasthenia gravis
Axon
Mitochondrion
Nerve terminal
ACh receptors
Muscle fiber
ACh
Synaptic
vesicle
AChesterase
A
B
FIGURE 36-6.
Neuromuscular
junction.
(A)
Acetylcholine (ACh)
released from the motor neurons in
the myoneural junction crosses the
synaptic space to reach receptors
that are concentrated in the folds
of the endplate of the muscle fiber.
Once released, ACh is rapidly
broken down by the enzyme
acetylcholinesterase (AChesterase).
(B)
Decrease in ACh receptors in
myasthenia gravis.
