Clinical Manifestations

The paralysis usually follows a nonspecific viral infection by about 10 days. The original infection might have caused only gastrointestinal (especially Campylobacter jejuni, but also Helicobacter pylori) or respiratory tract (especially Mycoplasma pneumoniae) symptoms. West Nile virus also can cause Guillain-Barré-like syndrome, but more often it causes motor neuron disease similar to poliomyelitis. Guillain-Barré syndrome is reported following administration of vaccines against rabies, influenza, and poliomyelitis (oral) and following administration of conjugated meningococcal vaccine, particularly serogroup C.

Weakness usually begins in the lower extremities and progressively involves the trunk, the upper limbs, and finally the bulbar muscles, a pattern known as Landry ascending paralysis. Proximal and distal muscles are involved relatively symmetrically, but asymmetry is found in 9% of patients. The onset is gradual and progresses over days or weeks. Particularly in cases with an abrupt onset, tenderness on palpation and pain in muscles is common in the initial stages. Affected children are irritable. Weakness can progress to inability or refusal to walk and later to flaccid tetraplegia. Paresthesias occur in some cases. The differential diagnosis of acute weakness is noted in Table 599-3 and of Guillain Barré syndrome in Table 608-1.

Bulbar involvement occurs in about half of cases. Respiratory insufficiency can result. Dysphagia and facial weakness are often impending signs of respiratory failure. They interfere with eating and increase the risk of aspiration. The facial nerves may be involved. Some young patients exhibit symptoms of viral meningitis or meningoencephalitis. Extraocular muscle involvement is rare, but in an uncommon variant, oculomotor and other cranial neuropathies are severe early in the course. Miller-Fisher syndrome consists of acute external ophthalmoplegia, ataxia, and areflexia. Papilledema is found in some cases, although visual impairment is not clinically evident. Urinary incontinence or retention of urine is a complication in about 20% of cases but is usually transient. Miller-Fisher syndrome overlaps with Bickerstaff brainstem encephalitis, which also shares many features with Guillain-Barré syndrome with lower motor neuron involvement and might indeed be the same basic disease.

Tendon reflexes are lost, usually early in the course, but are sometimes preserved until later. This variability can cause confusion when attempting early diagnosis. The autonomic nervous system is also involved in some cases. Lability of blood pressure and cardiac rate, postural hypotension, episodes of profound bradycardia, and occasional asystole occur. Cardiovascular monitoring is important. A few patients require insertion of a temporary venous cardiac pacemaker.

Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP, sometimes called chronic inflammatory relapsing polyneuritis or chronic unremitting polyradiculoneuropathy) are chronic varieties of Guillain-Barré syndrome that recur intermittently or do not improve or progress slowly and relentlessly for periods of months to years. About 7% of children with Guillain-Barré syndrome suffer an acute relapse. Patients are usually severely weak and can have a flaccid tetraplegia with or without bulbar and respiratory muscle involvement. Hyporeflexia or areflexia are almost universal. Motor deficits occur in 94% of cases, sensory paresthesias in 64%, and cranial nerve involvement in less than a third of patients. Autonomic and micturitional involvement is variable. CSF shows no pleocytosis and protein is variably normal or mildly elevated. Nerve conduction velocity (NCV) studies and sural nerve biopsy are abnormal. Polymorphic nucleotide repeats in the SH2D2A gene has been associated with a predisposition to CIDP.

Congenital Guillain-Barré syndrome is described rarely, manifesting as generalized hypotonia, weakness, and areflexia in an affected neonate, fulfilling all electrophysiologic and cerebrospinal fluid (CSF) criteria and in the absence of maternal neuromuscular disease. Treatment might not be required, and there is gradual improvement over the first few months and no evidence of residual disease by 1 yr of age. In 1 case, the mother had ulcerative colitis treated with prednisone and mesalamine from the 7th mo of gestation until delivery at term.

Table 608-2 CLASSIFICATION OF GUILLAIN-BARRÉ SYNDROME AND RELATED DISORDERS AND TYPICAL ANTIGANGLIOSIDE ANTIBODIES BY PATHOLOGY

From Hughes RAC: Treatment of Guillain-Barré syndrome with corticosteroids: lack of benefit? Lancet 363:181–182, 2004.

Laboratory Findings and Diagnosis

CSF studies are essential for diagnosis. The CSF protein is elevated to more than twice the upper limit of normal, glucose level is normal, and there is no pleocytosis. Fewer than 10 white blood cells/mm³ are found. The results of bacterial cultures are negative, and viral cultures rarely isolate specific viruses. The dissociation between high CSF protein and a lack of cellular response in a patient with an acute or subacute polyneuropathy is diagnostic of Guillain-Barré syndrome. MRI of the spinal cord may be indicated to rule out disorders in Table 608-1. MRI findings include thickening of the cauda equina and intrathecal nerve roots with gadolinium enhancement. These finds are fairly sensitive and are present in >90% of patients (Fig. 608-1). Imaging in CIDP is similar but demonstrates greater enhancement of spinal nerve roots (Fig. 608-2).

Figure 608-1 Guillain-Barré syndrome. Sagittal off-midline (A) and midline (B) postgadolinium T1-weighted fat-saturated images through the lumbar spine of a patient who could not ambulate. C and D, Axial postcontrast T1-weighted images through the conus medullaris and proximal lumbar nerve roots respectively. The images show extensive contrast enhancement of nerve roots (arrows in A-D), in keeping with changes of Guillain-Barré.

(From Slovis TL, editor: Caffey’s pediatric diagnostic imaging, ed 11, vol 1, Philadelphia, 2008, Mosby Elsevier, p 991.)

Figure 608-2 Chronic inflammatory demyelinating polyneuropathy (CIDP) in a 13-year-old boy with peripheral neuropathy and gait disturbance. Sagittal fat-saturated T1-weighted images off the midline to the right (A), at the midline (B), and off the midline to the left (C).

(From Slovis TL, editor: Caffey’s pediatric diagnostic imaging, ed 11, vol 1, Philadelphia, 2008, Mosby Elsevier, p 992.)

Motor NCVs are greatly reduced, and sensory nerve conduction time is often slow. Electromyography (EMG) shows evidence of acute denervation of muscle. Serum creatine kinase (CK) level may be mildly elevated or normal. Antiganglioside antibodies, mainly against G_M1 and G_D1, are sometimes elevated in the serum in Guillain-Barré syndrome, particularly in cases with primarily axonal rather than demyelinating neuropathy, and suggest that they might play a role in disease propagation and/or recovery in some cases (Table 608-1). Muscle biopsy is not usually required for diagnosis; specimens appear normal in early stages and show evidence of denervation atrophy in chronic stages. Sural nerve biopsy tissue shows segmental demyelination, focal inflammation, and wallerian degeneration but also is usually not required for diagnosis.

Serologic testing for Campylobacter and Helicobacter infections helps establish the cause if results are positive but does not alter the course of treatment. Results of stool cultures are rarely positive because the infection is self-limited and only occurs for about 3 days, and the neuropathy follows the acute gastroenteritis.

Treatment

Patients in early stages of this acute disease should be admitted to the hospital for observation because the ascending paralysis can rapidly involve respiratory muscles during the next 24 hr. Respiratory effort (negative inspiratory force, spirometry) must be monitored to prevent respiratory failure and respiratory arrest. Patients with slow progression might simply be observed for stabilization and spontaneous remission without treatment. Rapidly progressive ascending paralysis is treated with intravenous immunoglobulin (IVIG), administered for 2, 3, or 5 days. A commonly recommended protocol is IVIG 0.4 g/kg/day for 5 consecutive days. Plasmapheresis and/or immunosuppressive drugs are alternatives if IVIG is ineffective. Steroids are not effective. Combined administration of immunoglobulin and interferon is effective in some patients. Supportive care, such as respiratory support, prevention of decubiti in children with flaccid tetraplegia, and treatment of secondary bacterial infections, is important.

CIDPs, whether relapsing-remitting or unremitting, also are treated with oral or pulsed steroids or with IVIG. Subcutaneous immunoglobulin infusion may be an alternative to the intravenous route. Plasma exchange, sometimes requiring as many as 10 exchanges daily, is an alternative. Remission in these cases may be sustained, but relapses can occur within days, weeks, or even after many months; relapses usually respond to another course of plasmapheresis. Steroid and immunosuppressive drugs are another alternative, but their effectiveness is less predictable. High-dose pulsed methylprednisolone given intravenously is successful in some cases. The prognosis in chronic forms of the Guillain-Barré syndrome is more guarded than in the acute form, and many patients are left with major residual handicaps.

Even if C. jejuni infection is documented by stool culture or serologic tests, treatment of the infection is not necessary because it is self-limited, and the use of antibiotics does not alter the course of the polyneuropathy.

For the treatment of chronic neuropathic pain following Guillain-Barré syndrome, gabapentin is more effective than carbamazepine, and the requirement for fentanyl is reduced.

Prognosis

The clinical course is usually benign, and spontaneous recovery begins within 2-3 wk. Most patients regain full muscular strength, although some are left with residual weakness. The tendon reflexes are usually the last function to recover. Improvement usually follows a gradient opposite the direction of involvement: bulbar function recovering first, and lower extremity weakness resolving last. Bulbar and respiratory muscle involvement can lead to death if the syndrome is not recognized and treated. Although prognosis is generally good and the majority of children recover completely, 3 clinical features are predictive of poor outcome with sequelae: cranial nerve involvement, intubation, and maximum disability at the time of presentation. The electrophysiologic features of conduction block are predictive of good outcome. Long-term follow-up studies of patients who recover from an attack of Guillain-Barré syndrome reveal that many do have some permanent axonal loss, with or without residual clinical signs of chronic neuropathy. Easy fatigue is one of the most common chronic symptoms, but it is not the rapid fatigability of muscles seen in myasthenia gravis. Among patients with the axonal form of Guillain-Barré syndrome, most who had slow recovery over the first 6 mo could eventually walk, although some required years to recover. EMG and NCV electrophysiologic studies do not necessarily predict the long-term outcome.