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Nervous System
and thymectomy. Immunosuppressant drugs (e.g.,
azathioprine, cyclosporine) also may be used, often in
combination with plasmapheresis.
Plasmapheresis removes antibodies from the circula-
tion and provides short-term clinical improvement. It is
used primarily to stabilize the condition of persons in
myasthenic crisis or for short-term treatment in persons
undergoing thymectomy. Intravenous immunoglobulin
also produces improvement in persons with myasthenia
gravis. Although the effect is temporary, it may last for
weeks to months. Intravenous immunoglobulin therapy
is very expensive, which limits its use.
Thymectomy, or surgical removal of the thymus, may
be used as a treatment for myasthenia gravis. Because
the mechanism whereby surgery exerts its effect is
unknown, the treatment is controversial. Thymectomy
may be performed in persons with thymoma, regardless
of age, and in persons with generalized myasthenia gra-
vis with onset before 50 years of age.
16
Peripheral Nervous System Disorders
Peripheral nervous system (PNS) disorders involve neu-
rons that are located outside the CNS. They include
disorders of the motor and sensory branches of the
somatic and visceral nervous systems and the peripheral
branches of the autonomic nervous system (see Chapter
34). The result usually is muscle weakness, with or with-
out atrophy, and sensory changes.
Unlike the nerves of the CNS, peripheral nerves
are fairly strong and resilient. They contain a series of
connective tissue sheaths: the outer
epineurium
that
surrounds the medium-sized to large nerves, the
peri-
neurium
that invests each bundle of nerve fibers; and
the
endoneurium
that surrounds each nerve fiber (see
Chapter 34, Fig. 34-2). Inside the endoneurium are the
Schwann cells that produce the myelin sheath that sur-
rounds the peripheral nerves. Each Schwann cell can
myelinate only one segment of a single axon—the one
that it covers—so that myelination of an entire axon
requires the participation of a long line of these cells.
Peripheral Nerve Injury and Repair
There are two main types of peripheral nerve injury
based on the target of the insult: segmental demyelin-
ation involving the Schwann cell and axonal degenera-
tion involving the neuronal cell body or its axon.
8,17
Segmental Demyelination.
Segmental demyelination
occurs when there is a disorder of the Schwann cell (as
in hereditary motor and sensory neuropathies) or dam-
age to the myelin sheath (e.g., Guillain-Barré syndrome)
without a primary abnormality of the axon. It typically
affects some Schwann cells while sparing others. The dis-
integrated myelin is engulfed initially by Schwann cells
and then by macrophages. The denuded axon provides
a stimulus for remyelination and the population of cells
within the endoneurium has the capacity to replace the
injured Schwann cells. These cells proliferate and encircle
the axon, and in time remyelinate the denuded portion.
Axonal Degeneration.
Axonal degeneration is caused
by primary injury to a neuronal cell body or its axon.
Damage to the axon may be due either to a focal event
occurring at some point along the length of the nerve
(e.g., trauma or ischemia) or to a more generalized abnor-
mality affecting the neuronal cell body (neuropathy).
Damage to a peripheral nerve axon, whether by
injury or neuropathy, results in degenerative changes,
followed by breakdown of the myelin sheath and
Schwann cells. In distal axonal degeneration, the proxi-
mal axon and neuronal cell body, which synthesizes the
material required for nourishing and maintaining the
axon, remain intact. In neuropathies and crushing inju-
ries, in which the endoneurial tube remains intact, the
outgrowing fiber grows down this tube to the structure
that was originally innervated by the neuron (Fig. 36-7).
However, it can take weeks or months for the regrowing
fiber to reach its target organ and for communicative
function to be reestablished. More time is required for
the Schwann cells to form new myelin segments and for
the axon to recover its original diameter and conduction
velocity.
Basement
membrane
Axonic termination at
neuromuscular junction
Schwann
myelin
Level
of
crush
Collagen
CNS
PNS
FIGURE 36-7.
Sequential stages of efferent axon degeneration
and regeneration within its endoneurial tube, after peripheral
nerve crush injury. CNS, Central nervous system; PNS,
Peripheral nervous system.
