eMedicine Specialties > Neurology > Pediatric Neurology

Guillain-Barre Syndrome in Childhood

Author: Brian S Tseng, MD, PhD, Assistant Professor, Department of Neurology, Division of Pediatric Neurology, Harvard Medical School, Massachusetts General Hospital
Coauthor(s): Jennifer A Markowitz, MD, Fellow in Neuromuscular Disease, Massachusetts General Hospital and Brigham and Women's Hospital
Contributor Information and Disclosures

Updated: Sep 18, 2008

Introduction

Background

Guillain-Barré syndrome (GBS), or acute inflammatory demyelinating polyradiculoneuropathy (AIDP), is characterized by progressive motor weakness and areflexia. Sensory, autonomic, and brainstem abnormalities are also common. These symptoms usually follow a febrile and/or viral illness. With the eradication of poliomyelitis, GBS is the most common cause of acute motor paralysis in children.

The first modern description of an illness likely to be AIDP was published by Landry in 1859. Osler provided a more detailed account of what he called acute febrile polyneuritis in 1892. In 1916, Guillain, Barré, and Strohl further enlarged the clinical description and first reported the characteristic cerebrospinal fluid (CSF) finding, albuminocytologic dissociation (ie, elevation of CSF protein with normal CSF cell count). The CSF findings, in combination with certain clinical features, allowed AIDP to be distinguished from anterior horn cell diseases such as poliomyelitis and from other neuropathies.

For a CME activity, see Routine Vaccination With Quadrivalent Meningococcal Conjugate Vaccine Not Recommended for Certain Children.

Pathophysiology

Demyelinating and axonal forms of GBS have both been described. In the demyelinating form, segmental demyelination of peripheral nerves is found in association with infiltration of inflammatory cells. GBS with axonal degeneration may occur without demyelination or inflammation.

Many authors believe that the mechanism of disease involves an abnormal T-cell response precipitated by a preceding infection. Some of the pathogenic triggers of GBS include Epstein-Barr virus, cytomegalovirus, hepatitis, varicella, Mycoplasma pneumonia, and Campylobacter jejuni, perhaps most common. These pathogens are believed to activate CD4⁺ helper-inducer T cells, which are particularly important mediators of disease. A variety of specific endogenous antigens including myelin P-2, ganglioside GQ1b, GM1, and GT1a may be involved in this response. Molecular mimicry of the triggering pathogens resembling antigens on peripheral nerves leads to an overzealous and autoimmune response mounted by T-cell lymphocytes and macrophages.

Frequency

United States

Estimates of annual incidence of GBS range from 0.5-1.5 per 100,000 in individuals younger than 18 years. No clear seasonal preponderance of GBS has been noted in the United States although some seasonal variation is reported in neighboring Mexico.

International

Risk of occurrence is similar throughout the world, in all climates, and among all races, except for reports of seasonal predilections noted in some countries for Campylobacter -related GBS in the summer and upper respiratory illness—related GBS in the winter. Recently, epidemics of an illness closely resembling GBS were noted to occur annually in the rural areas of North China, particularly during the summer months. These epidemics have been associated with C jejuni infection, and many of these patients are found to have antiglycolipid antibodies. Because these cases involve degeneration of peripheral motor axons without much inflammation, the syndrome has been termed acute motor axonal neuropathy (AMAN). Recently, other region-specific demographic studies have shown discrete preponderance of AMAN. For example, in a prospective pediatric study (n=78) from Mexico, AMAN seemed to exhibit a seasonal peak from July-September unlike AIDP, which seemed to be more evenly distributed throughout the year.¹

Mortality/Morbidity

Overall mortality rate in childhood GBS is estimated to be less than 5%; mortality rates are higher in medically underserved areas. Deaths are usually caused by respiratory failure, often in association with cardiac arrhythmias and dysautonomia. Full recovery within 3-12 months is experienced by 90-95% of pediatric patients with GBS. Between 5% and 10% of individuals have significant permanent disability.

• In general, the outcome of GBS is more favorable in children than in adults. Deaths are relatively rare, especially if recognition of the signs of this disorder are acted upon quickly. The recovery period is longer than the duration of the acute illness, often weeks to months, with a median estimated recovery time of 6-12 months. In one small pediatric series, the median time from onset of symptoms to complete recovery was 73 days.
• The most common serious complications are weakness of the respiratory muscles and autonomic instability. Pneumonia, adult respiratory distress syndrome, septicemia, pressure sores, ileus, constipation, gastritis, dysesthesias, and pulmonary embolus are also important potential complications. During the acute progressive phase of the disease, close attention should be paid to respiratory status.
  • In cooperative children older than 5 years, respiratory function measurements such as vital capacity or maximal inspiratory force (MIF), expressed in units of cc H₂ O pressure can be valuable. MIFs are also known as negative inspiratory force (NIF). MIFs less than -20 cc H₂ O pressure can be an indication of poor inspiratory ability and respiratory distress. MIFs are normally greater than -40 cc H₂ O pressure, thus the more negative, the better MIF.
  • MIFs provide objective data to follow and compare. This measure is unfortunately difficult to monitor in young (<5 y) and any uncooperative child. Experienced pediatric respiratory therapists can be very valuable in these measures.
  • Blood gases and chest radiographs are also valuable in assessing respiratory parameters.
• Recurrence of GBS occurs in approximately 5% of cases, sometimes many years after the initial bout. Recurrence is generally thought to be relatively uncommon in children but has been reported in one small series to be observed in nearly 12% of cases in the first 2-3 weeks after intravenous immunoglobulin (IVIG) administration.
• Some patients experience a chronic progressive course, known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Race

Although major histocompatibility locus genes may play a role in susceptibility to GBS, no evidence exists for any racial predilection.

Sex

Males appear to be at greater risk for GBS than females. This increased predilection for GBS has also been reported as a male-to-female ratio of 1.2:1 in a recent review of children with GBS. A similar ratio of 1.26:1 was found in a prospective study of 95 children with GBS in Western Europe.²  In a prospective study of 78 children from Mexico, acute inflammatory demyelinative polyneuropathy (AIDP) was 3 times more common in male patients than in female patients, while acute motor axonal neuropathy (AMAN) was slightly more common in males than in females .¹  In Pakistan, a combined adult and pediatric Guillain-Barré study (n=175) reported that 68% of all patients were male.3

Age

Individuals older than 40 years have a steadily increasing risk, peaking at age 70-80 years, compared with younger individuals. Children are at lower risk than adults, with incidence ranging from 0.5-1.5 per 100,000 children.

Recent retrospective reviews of childhood GBS reported the average age to be in the range of 4-8 years. Individuals affected with GBS can be as young as 1 year.

Clinical

History

• Patients with Guillain-Barré syndrome (GBS) present with complaints of weakness and/or unsteadiness (ataxia). Pain and dysesthesias also are noted, particularly in children. Often, onset of these symptoms is within 2-4 weeks of an illness or immunization. Urinary retention is also noted early in the course of 10-15% of children with GBS.
• Weakness is a hallmark of GBS. The weakness typically starts in the lower extremities and ascends to the upper extremities (hence, the description progressive ascending flaccid paralysis). This progression may occur over hours to days to weeks. The weakness is symmetric, occurring on both sides of the body in most cases. Usually, patients give a history of a preceding illness that involves fever, muscle pains, and upper respiratory illness. Some would claim that vomiting may be more predictive of acute inflammatory demyelinating polyneuropathy (AIDP) while diarrhea may be a harbinger of acute motor axonal neuropathy (AMAN).
• Pain may be the initial manifestation in almost half of affected children. Because of the prominence of pain, some children are misdiagnosed initially.
• Autonomic symptoms (eg, dizziness secondary to orthostatic hypotension) and tachycardia also can occur.
• Unsteadiness is often due to the weakness itself. However, the Miller-Fisher variant, which also can be seen in children, is characterized by ophthalmoplegia, ataxia, and areflexia with relatively little weakness. Such affected patients with Miller-Fischer triad are generally not thought to be at as great a risk for severe respiratory compromise.
• Clinical spectrum of GBS, which will include individual variation and variable severity of presentation.
  • AIDP
  • AMAN
  • Acute motor and sensory axonal neuropathy (AMSAN)
  • Miller-Fischer syndrome (MFS)
  • Polyneuritis cranialis
  • Pharyngo-cervical-brachial syndrome
  • Acute sensory neuropathy of childhood
  • Acute pandysautonomia

Physical

• On physical examination, an ascending motor weakness is noted along with areflexia in the classic form. Occasionally, autonomic instability (26%), ataxia (23%), dysesthesias (20%), and cranial nerve findings (35-50%) are noted. These latter findings are probably more frequent in children than in adults with this syndrome.
• Leg weakness (ie, foot drop) is usually noticed first and weakness eventually involves the calves and thighs. Later, respiratory muscles and upper extremities show involvement. Some children may become non-ambulatory. Weakness also may involve the respiratory muscles, and some children need respiratory support during the course of the disease. Mechanical ventilation is used until respiratory muscle function returns.
• Areflexia is a hallmark of GBS. Occasionally, some of the more proximal reflexes still may be elicited during the early phase of the disease. Of clinical value is documenting reflexes in serial exams; the progression from normoreflexia/hyporeflexia to areflexia is consistent with acute features of GBS.
• The autonomic neuropathy involves both the sympathetic and parasympathetic systems. Manifestations include orthostatic hypotension, hypertension, pupillary dysfunction, sweating abnormalities, and sinus tachycardia.

Causes

• GBS is an autoimmune-mediated disease with environmental triggers (eg, pathogenic or stressful exposures).
• Several infections (eg, Epstein-Barr virus, cytomegalovirus, hepatitis, varicella, other herpes viruses, Mycoplasma pneumoniae, C jejuni) as well as immunizations have been known to precede or to be associated with the illness. C jejuni seems to be the most commonly described pathogen associated with GBS. Occasionally, surgery has been noted to be a precipitating factor.
• Many forms of GBS are demyelinating. However, more recently, an axonal form of GBS has been described after a diarrheal illness secondary to C jejuni.
• Other diseases can present with a GBS-like picture.
• The differential diagnosis of GBS in childhood is primarily in the spectrum of progressive, symmetric weakness.
• In infants, botulism should be a consideration. Botulism is characterized not only by weakness but also by involvement of the extraocular muscles and constipation. Pupillary abnormalities can be an important distinguishing feature unique to botulism.
• When ophthalmoplegia is present, myasthenia gravis should be considered. Occasionally, myasthenia gravis can present with primarily proximal weakness in childhood. Nerve conduction velocity (NCV) and electromyography (EMG) findings, including repetitive stimulation, can help distinguish myasthenia gravis from GBS.
• GBS-like syndromes can occur in certain infections, such as Lyme disease or HIV. In these cases, lumbar puncture (LP) results typically show a CSF pleocytosis.
• Myelopathies also can present sometimes with progressive weakness, and the physical examination should help differentiate a spinal cord syndrome from a diffuse neuropathy. Transverse myelitis can also produce a rapidly progressive paralysis, hyporeflexia, and back pain. Poliomyelitis and other enteroviral infections of the anterior horn cell cause acute focal, asymmetric limb weakness, usually in association with fever and pain.
• Other acute neuropathies, caused by lead, heavy metals, or vincristine, can cause a predominantly motor neuropathy.
• Tick infestation can cause an ascending paralysis, and children should be searched for ticks if they present with these symptoms. Often, the clinical syndrome improves dramatically after removal of ticks. In the Eastern states of United States, the most concerning tick is called Dermacentor variabilis.
• Occasionally, organophosphate poisoning may present with a GBS-like picture.

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