Drugs and environmental toxins that interfere with axonal transport or cytoskeletal function often produce peripheral neuropathies. The longest axons are most susceptible, hence symptoms appear first and are most pronounced in the distal extremities.
Peripheral nerves are damaged in many different forms of systemic vasculitis (
Fig. 22.2B ) (Chapter 10), including polyarteritis nodosa, Churg-Strauss syndrome, and polyangiitis with granulomatosis. Overall, peripheral nerve damage is seen in about a third of all patients with vasculitis at the time of presentation. The most common clinical picture is that of mononeuritis multiplex with a painful asymmetric mixed sensory and motor peripheral neuropathy. Patchy involvement also is apparent at the microscopic level, as single nerves may show considerable interfascicular variation in the degree of axonal damage (
Fig. 22.2C
Inherited diseases of peripheral nerves are a heterogeneous but relatively common group of disorders, with a prevalence of 1 to 4 in 10,000. They can be demyelinating or axonal. Many such disorders manifest in adulthood and follow a slowly progressive course that may mimic that of acquired polyneuropathies. The most common causes are mutations in the genes encoding myelin-associated proteins.
Peripheralneuropathiesmayresultinweaknessand/orsensorydeficitsinpatternsdescribedaspolyneuropathy,mononeuritismultiplex,andmononeuropathy.
Axonalanddemyelinatingperipheralneuropathiescanbedistinguishedonthebasisofclinicalandpathologicfeatures.Somedisordersareassociatedwithamixedpatternofinjury.
Diabetesisthemostcommoncauseofperipheralneuropathy.
Guillain-Barrésyndromeandchronicidiopathicdemyelinatingpolyneuropathyareimmune-mediateddemyelinatingdiseasesthatfollowacuteandchroniccourses,respectively.
Metabolicdiseases,drugs,toxins,connectivetissuediseases,vasculitides,andinfectionsallcanresultinperipheralneuropathy.
Anumberofmutationscauseperipheralneuropathy.Manyoftheseareadult-onsetdiseasesthatmaymimicacquiredones.
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The neuromuscular junction is a complex specialized structure located at the interface of motor nerve axons and skeletal muscle that serves to control muscle contraction. Here the distal ends of peripheral motor nerves branch into small processes that terminate in bulbous synaptic boutons. Nerve impulses depolarize the presynaptic membrane, stimulating calcium influx and the release of acetylcholine into the synaptic cleft. Acetylcholine diffuses across the synaptic cleft to bind its receptor on the postsynaptic membrane, leading to depolarization of the myofiber and contraction through electromechanical coupling. Often disorders of the neuromuscular junction produce functional deficits in the absence of any significant alterations in morphology beyond ultrastructural changes. Considered in this section are some of the more common or pathogenically interesting disorders that disrupt the transmission of signals across the neuromuscular junction.