Page 936 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Autoimmune Peripheral Neuropathies

Marinos C. Dalakas

Autoimmune peripheral neuropathies (APNs) occur when motor or sensory nerve fibers and the myelin sheath or the axon.
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immunological tolerance to peripheral nerve components The GBS subtypes, or GBS variants, include:
(myelin, Schwann cell, axon, and motor or ganglionic neurons) • Acute inflammatory demyelinating polyneuropathy (AIDP),
is lost. In some of these neuropathies, there is direct evidence which accounts for the majority (probably 80%) of patients.
for autoimmune reactivity mediated by specific antibodies or In classic cases, the weakness starts from the legs and spreads
autoreactive T lymphocytes against peripheral nerve. In others, up to the arms, intercostal and diaphragmatic muscles, and
the underlying immune-mediated mechanism is secondary facial or bulbar muscles, causing dysphagia and dysarthria.
or indirect, and an autoimmune cause is suspected when the At times the weakness may be limited to one or two limbs
neuropathy coexists with another systemic autoimmune disease or to cranial nerves. Patients need to be monitored for impend-
or viral infection. ing respiratory failure, hence the need for early admission to
This chapter reviews the most common autoimmune neu- intensive care units (ICUs). Autonomic dysfunction occurs
ropathies (Table 67.1), their clinical features and diagnostic in varying degrees in up to 65% of patients; if severe, it can
criteria, the prevailing autoimmune phenomena that govern each be life-threatening as a result of cardiac arrhythmias or
neuropathy, and the most effective therapeutic approach. hemodynamic changes, such as hypertension, orthostatic
hypotension, and reduced peripheral vascular tone. 1-5
ACUTE INFLAMMATORY POLYNEUROPATHY: • Acute motor axonal neuropathy (AMAN), which exhibits
GUILLAIN-BARRÉ SYNDROME(S) primary axonal damage caused by massive acute demyelination
and inflammation, as occurs in experimental allergic neuritis
Guillain-Barré syndrome (GBS) is an acute demyelinating (EAN) when the animals are immunized with a high dose of
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polyneuropathy characterized by acute (within 1 week) or myelin antigen, or by a primary axonal event mediated by
subacute (within 4 weeks) ascending motor weakness, mild macrophages. These patients have a fulminant course with
or moderate sensory abnormalities, occasional cranial nerve severe paralysis and complete electrical inexcitability of motor
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involvement, and muscle or radicular pain. Tendon reflexes nerves as early as 3–5 days after onset. In contrast to AIDP,
are reduced but can be normal, especially in axonal GBS. It involvement of cranial nerves is infrequent, and reflexes are
is a disease of all ages, with an incidence of 0.8–1.9 (median normal or increased, especially early in the disease. AMAN is
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1.1) per 100 000, and occurs sporadically, although occasional common in Asia and Central South America, accounting for
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outbreaks have been noted. In typical cases, the maximum 30–65% of all GBS cases in these regions. Recovery of motor
deficit is reached by the fourth week, a sign conventionally function is variable; some patients recover within days as a
used to separate GBS from chronic inflammatory demyelinating result of resolution of conduction block, but others have slow
polyneuropathy (CIDP), in which the disease begins slowly and and poor recovery because of excessive axonal degeneration at
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usually reaches a nadir after at least 2 months. There are, however, the root level. Infection with Campylobacter jejuni appears to
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patients with CIDP (perhaps up to 16%) with subacute onset be responsible for many of these cases. A number of patients
and monophasic course and fall between the two time-frames also have high levels of antiganglioside GM1 antibodies. 1-7
and still others with an even more acute onset, reaching a nadir • Acute motor–sensory axonal neuropathy (AMSAN) is similar
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within 6–8 weeks and resembling GBS. Distinguishing GBS to AMAN, but with concurrent involvement of the sensory
from acute-onset CIDP is challenging because the distinction, axons, and has a pathomechanism similar to that of AMAN,
in most cases, becomes evident in retrospect, although pro- including frequent antibodies against GM1 and GD1a gan-
posed criteria may help separate the two early in the disease gliosides following C. jejuni infection.
course. 1-5 • Miller Fisher syndrome (MFS) is characterized by acute onset
After reaching the clinical peak, there is a recovery period of ophthalmoplegia, gait ataxia, normal sensation, and
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that varies from weeks to years according to disease subtype or areflexia. In a third of patients, there is muscle weakness
severity at onset; rapid initial progression over <7 days, severity with pharyngeal, facial, trunk, and respiratory muscle involve-
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at onset requiring mechanical ventilation, age >60 years, and ment; rarely it can present as an isolated ocular nerve palsy.
preceding diarrheal illness are signs associated with incomplete MFS is a variant that is distinct because of the presence of a
recovery or worse outcome. GBS is not one syndrome, but several unique immunoglobulin G (IgG) antibody against GQ1b
syndromes, reflecting the varying degree of involvement of the ganglioside. 1-7
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