Porth's Essentials of Pathophysiology, 4e

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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

CNS

PNS

Collagen

Level of crush

Schwann myelin

Axonic termination at neuromuscular junction

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.