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Acute Polyneuropathies


Introduction

The acute polyneuropathies are a group of acquired, generally immune-mediated or infectious disorders causing dysfunction and sometimes degeneration of peripheral nerves, spinal sensory and motor nerve roots, and occasionally the cranial nerves. The most common of these conditions are the Guillain-Barré syndrome and its variants. This chapter will also cover the presentation and treatment of tick paralysis.

Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy that is most often characterized by rapidly progressive, essentially symmetric weakness and areflexia in a previously well child. Weakness is usually distally predominant, at least at onset, but an initially proximal pattern of weakness is seen in 15–20% of children, and cranial nerve involvement is common in pediatric GBS. Distal paresthesias and neuropathic pain are prominent in many affected children. The neurologic deficit of GBS progresses over a few days to a month. The clinical diagnosis of GBS is confirmed by the findings of cytoalbuminologic dissociation (elevation of the cerebrospinal fluid (CSF) protein without concomitant CSF pleocytosis), and by neurophysiologic abnormalities suggesting an acute (usually demyelinating) neuropathy. These abnormalities are not always present in the early stages of the illness. Diagnostic criteria for GBS have been suggested but do not encompass the full spectrum of this disorder, so that the diagnosis is based on consistent clinical, laboratory, and neurophysiologic findings with exclusion of alternate diagnoses ( Box 20.1 ).

Box 20.1
Diagnostic Criteria for Guillain-Barré Syndrome
Modified from Asbury and Cornblath.

  • Development of essentially symmetric limb weakness in arms and legs—may start in legs only

  • Cranial nerve involvement

  • Loss or decrease in muscle stretch reflexes within 1 week of onset

  • Autonomic instability

  • Pain in neck, back, or extremities—often poorly localized

  • Progression of these features over several days to 4 weeks

  • Paresthesias of the hands and feet

Features casting doubt on the diagnosis of GBS:

  • Persistent asymmetry of weakness

  • Identifiable sensory level

  • Prominent and persisting bladder or bowel dysfunction

  • More than 50 mononuclear cells/mm 3 in CSF

  • Polymorphonuclear cells in CSF

Laboratory abnormalities that support the diagnosis:

  • Elevation of CSF protein >45 mg/dL within 3 weeks of onset

  • Neurophysiologic abnormalities consistent with an acute inflammatory polyneuropathy in at least two limbs:

    • 1.

      Slowing of motor and sensory nerve conduction (<80% of lower limit of normal values for age)

    • 2.

      Conduction block or temporal dispersion of compound muscle action potentials (CMAPs)

    • 3.

      Increased distal latencies

    • 4.

      Abnormalities of F waves (loss, impersistence, dispersion)

    • 5.

      Criteria for axonal forms include lack of neurophysiologic evidence of demyelination, with loss or dispersion of CMAP or sensory nerve action potential amplitudes to at least <80% of lower limit of normal values for age

In the post-polio era, GBS is the most common cause of acute flaccid paralysis in childhood, with an annual incidence of 0.34–1.34 cases per 100,000 persons aged 18 years or less. GBS is slightly more common in males. It occurs worldwide, affecting all age groups and ethnicities, with an increase in frequency in each decade of life. Rare cases develop in utero or in the neonatal period. Variation in the incidence of GBS in different populations, and the occasional reports of familial cases of GBS, may reflect variable genetic susceptibility or geographic exposure to causative pathogens.

Clinical Findings

In 50–70% of cases, GBS develops 2–4 weeks after a prodromal gastroenteritic or respiratory illness, such as those caused by Epstein-Barr virus, cytomegalovirus, Mycoplasma pneumoniae , hepatitis, varicella, and other herpesviruses. Campylobacter jejuni is the most common infectious agent associated with axonal forms of GBS while cytomegalovirus infection causes a form of GBS with prominent sensory symptoms and involvement of the cranial nerves. The incidence of GBS after C. jejuni infection, however, is only 0.25–0.65/1000 cases. Occasional cases follow immunization or surgery, or develop in association with other illnesses, but childhood GBS has not been proven to result from vaccination against poliomyelitis, tetanus, or measles. Uncommonly, GBS may be the presenting manifestation of primary central nervous system or systemic lymphoma.

GBS can occur at any age. Occasional congenital and neonatal cases have been described, with vertical transmission between an affected mother and fetus also having been reported on several occasions. As a treatable cause of neonatal hypotonia, GBS should therefore be included in the differential diagnosis of the “floppy infant.” Approximately one-third of childhood cases occur before the age of 3 years.

Infants with GBS present with hypotonia and decreased movement, and sometimes with respiratory insufficiency. Irritability may be prominent. Diagnosis of infantile GBS is often delayed.

Older children usually complain of weakness and fatigue, paresthesias and pain, and have difficulty walking, rising from the floor, and climbing stairs. Weakness is generally symmetrical, starting in the lower extremities and then ascending into the upper extremities over days to weeks, and remaining distally predominant throughout the course of the illness. In a significant proportion (15–20%) of cases, however, weakness is primarily proximal. Cranial nerve involvement is more common in pediatric than adult GBS. Facial weakness and ophthalmoplegia are seen in up to 45% of affected children. Internal ophthalmoplegia is rare in GBS and should prompt consideration of tick paralysis, diphtheria, and botulism.

Neck, back, buttock, or leg pain, which is presumed to result from nerve root and peripheral nerve inflammation, is the initial manifestation in as many as 50% of children with GBS. This pain is often poorly localized and may cause marked irritability. Recognition of this symptom is especially important in young children who may be unable to describe weakness, and in whom pain and refusal to weight-bear is often initially thought to result from orthopedic or rheumatologic causes. The severity of pain tends to broadly correspond to the degree of weakness.

As many as 50% of children with GBS have ataxia resulting from weakness and sensory loss (“deafferentation”) rather than from cerebellar involvement. Rare cases of pediatric GBS present as the Miller Fisher variant of ataxia, ophthalmoplegia, and areflexia without peripheral weakness.

Respiratory muscle weakness in GBS is usually slowly progressive and tends to correlate with the degree of limb muscle weakness. Very rare cases of pediatric GBS present with acute-onset respiratory failure, which is life-threatening and may be associated with complete flaccid paralysis. Such severe and acute cases should prompt consideration of an underlying genetic neuropathy.

Meningism, headache, drowsiness, and irritability are seen occasionally in children presenting with a “pseudo-encephalopathic” form of GBS that mimics acute meningitis or meningoencephalitis. There are several reports of locked-in syndrome in children with severe GBS presenting with quadriparesis, areflexia, respiratory failure, and cranial nerve dysfunction. Neurophysiologic studies show inexcitable peripheral nerves. The prognosis of such cases is poor.

By definition GBS has a rapid course, reaching a maximal deficit within 4 weeks, although as many as 80% of children reach their clinical nadir within 2 weeks of onset. At their nadir 60% of children cannot walk, and 24% lose functional movement of their arms.

Physical examination reveals weakness, which ascends from the distal lower extremities over days–weeks, and loss of the muscle stretch reflexes. These changes may be quite patchy and can be asymmetric, especially at onset. Weakness usually begins in the legs and progresses rostrally, but can be proximally predominant at onset. The deep tendon reflexes are usually lost within the first week of the illness, but are occasionally preserved throughout its course. Rare cases of hyperreflexia in GBS are usually associated with the acute motor axonal variant of this condition.

Sensory loss is rarely prominent in childhood GBS, but can be identified on detailed examination in about 40% of cases. Identification of a sensory level is not compatible with GBS and should prompt immediate consideration of spinal cord pathology.

Involvement of the autonomic nervous system is seen in 25–50% of children with GBS, usually manifesting as blood pressure instability, sinus tachycardia, pupillary abnormalities, and abnormalities of sweating. Autonomic instability and urinary incontinence are more common in atypical or focal forms of pediatric GBS. Recent reports of hypertensive encephalopathy and posterior reversible encephalopathy as initial manifestations of GBS highlight the importance of considering this condition as part of the differential diagnosis of any acute dysautonomia.

Sphincter dysfunction (urinary retention, urinary and fecal incontinence) is occasionally seen in children with GBS but is far more common in transverse myelitis, tumors, and other spinal cord lesions. Although urinary retention occurs in 10–15% of children early in the course of GBS, persistent bladder or bowel involvement are indications for spinal imaging.

Clinical Variants of Guillain-Barré Syndrome

The various clinical subtypes of GBS are defined by their differential involvement of motor and sensory axons of peripheral nerves ( Table 20.1 ). In most populations, the most common form of GBS is acute inflammatory demyelinating polyneuropathy, which in most series accounts for about 75% of cases, while acute motor axonal neuropathy most often occurs in outbreaks associated with Campylobacter jejuni infection.

Table 20.1
Clinical Variants of Guillain-Barré Syndrome in Childhood
Clinical Syndrome Relative Frequency IgG Antiganglioside Antibody Association(s)
Acute inflammatory demyelinating polyneuropathy Common GM1 (minority)
Acute motor axonal neuropathy Common GM1, GD1a
Acute motor and sensory axonal neuropathy Uncommon GM1, GD1a
Miller Fisher syndrome Uncommon GQ1b, GT1a
Pharyngeal-cervical-brachial variant Rare GT1a, GQ1b, GD1a
Polyneuritis cranialis Rare GQ1b, GT1a
Acute (ataxic) sensory neuropathy Very rare GQ1b, GT1a
Acute pandysautonomia Very rare
Acute ophthalmoparesis Very rare GQ1b, GT1a

Acute Inflammatory Demyelinating Polyneuropathy

Acute inflammatory demyelinating polyneuropathy (AIDP) is the classic form of the Guillain-Barré syndrome and its most common subtype in Western nations. This acute immune-mediated neuropathy is thought to reflect injury, mediated by activated T cells and antibody responses, to Schwann cell and myelin epitopes in spinal roots and peripheral nerves. The antibody responses are poorly understood, as AIDP is only infrequently linked to specific antibodies against peripheral nerve gangliosides and glycolipids. The pathologic correlates of AIDP include inflammatory infiltrates in affected nerve segments, with concomitant macrophage-mediated vesicular demyelination along the course of sensory and motor axons. The neurophysiologic correlates include patchy, multifocal slowing of nerve conduction, conduction block, and loss of late responses. The clinical deficits resulting from these processes are determined by the severity of conduction block and the degree of concomitant axonal degeneration.

Acute Motor Axonal Neuropathy

The acute motor axonal neuropathy (AMAN) form of GBS was originally described in southern Mexico, and subsequently found to underpin epidemics of acute flaccid paralysis following Campylobacter jejuni enteritis in Chinese children. C. jejuni expresses lipo-oligosaccharides which resemble the carbohydrate component of gangliosides. AMAN mimics AIDP clinically, but the fulminant motor deficits of AMAN are unassociated with sensory deficits. Neurophysiologic studies in AMAN show normal speed of peripheral nerve conduction, decreased amplitude and dispersion of compound motor action potential (CMAP) amplitudes with normal sensory responses, and electromyographic evidence of denervation. Pathology studies confirm the discrete involvement of peripheral motor axons, with sparing of dorsal spinal nerve roots and sensory axons. Nerve histology shows inflammatory mononuclear infiltrates with macrophage-mediated phagocytosis of motor axons. This inflammation is often associated with development of IgG antibodies against the GM1 and/or GD1a gangliosides. Although the peripheral nerve axon is the primary immunologic target in this disorder, its clinical course and tempo of recovery are often very similar to AIDP, suggesting that most nerve injury is either due to antibody-mediated paranodal or very distal nerve injury, and hence quickly repaired.

Acute Motor-Sensory Axonal Neuropathy

The acute motor-sensory axonal neuropathy (AMSAN) variant is a rare, severe form of GBS. Like AMAN, the clinical presentation of AMSAN may be indistinguishable from AIDP, but neurophysiologic studies show pure axonal changes (diminished CMAP and sensory nerve action potential amplitudes, with relative preservation of motor and sensory nerve conduction velocities). In severe cases peripheral nerve responses may not be recordable. There is evidence of denervation on EMG. The histopathologic features reflect severe degeneration of motor and sensory axons. Differentiation of AMSAN from AIDP is contingent on the neurophysiologic findings, and is important because children with the former generally have a more severe deficit with a slower, often incomplete recovery.

Miller Fisher Syndrome and the Pharyngo-Cervical-Brachial Variant of GBS

Although generally attributed to C. Miller Fisher, this clinical syndrome of ophthalmoparesis, ataxia, and areflexia was initially recognized as a GBS variant by Georges Guillain himself in 1916. Bulbar weakness may also be present, and children initially presenting with these findings often later evolve truncal and limb weakness. Neurophysiologic testing may show loss of late responses (F waves and/or H responses), and there is often slowing of peripheral nerve conduction or evidence of an axonal neuropathy. Formes fruste of Miller Fisher syndrome (MFS) include isolated acute ptosis or ophthalmoplegia, with or without ataxia, while Bickerstaff’s brainstem encephalitis may present as MFS with additional long-tract signs attributable to central nervous system involvement. Most patients eventually recover completely. MFS is often associated with circulating IgG and IgM antibodies to the GQ1b and/or GT1a gangliosides, glycolipids expressed on the axolemmal membrane of cranial nerves. The CSF protein is generally normal in the first week but elevated by the second or third week of the illness.

The pharyngo-cervical-brachial variant of GBS also has a regional predominance, but can be associated with late evolution of more generalized weakness, disseminated changes on nerve conduction studies, and antibodies to GT1a or/or GQ1b. In practice these clinical syndromes overlap quite significantly. All tend to recover quickly.

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