Pediatric Guillain-Barre Syndrome
- Author: Marc P DiFazio, MD; Chief Editor: Amy Kao, MD more...
Guillain-Barré syndrome (GBS), or acute inflammatory demyelinating polyradiculoneuropathy (AIDP), describes a heterogeneous condition with a number of redundant variants. The classic presentation is characterized by an acute monophasic, non-febrile, post-infectious illness manifesting as ascending weakness and areflexia. Sensory, autonomic, and brainstem abnormalities may also be seen. With the eradication of poliomyelitis, GBS is the most common cause of acute motor paralysis in children.
The pathogenesis of GBS remains unclear. Increasing data indicate that it is an autoimmune disease, often triggered by a preceding viral or bacterial infection with organisms such as Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, or Mycoplasma pneumoniae. Vaccination against the flu, rabies, and meningitis are also documented precipitating factors that have been reported.
The diagnosis of GBS is typically based on the presence of a progressive ascending weakness with areflexia (see Workup). To date, treatment for GBS has been aimed primarily at immunomodulation. In pediatrics, the most effective form of therapy is generally considered to be intravenous immunoglobulin (IVIG) (see Treatment). In general, the outcome of GBS is more favorable in children than in adults; however, the recovery period is long, often weeks to months (see Prognosis). Rarely, it can be fatal in 5-10% of patients with respiratory failure and cardiac arrhythmia.
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 broadened 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, spinal muscular atrophy and from other neuropathies.
Demyelinating and axonal forms of GBS have both been described. In the demyelinating form, segmental demyelination of peripheral nerves is thought to be immune mediated and both humoral and cell-mediated immune mechanisms have been implicated. GBS with axonal degeneration may occur without demyelination or inflammation.
Roughly two thirds of patients have a history of an antecedent gastrointestinal or respiratory tract infection. Many authors believe that the mechanism of disease involves an abnormal T-cell response precipitated by an infection.
Some of the pathogenic triggers of GBS include Epstein-Barr virus, cytomegalovirus, the enteroviruses, hepatitis A and B, varicella, Mycoplasma pneumoniae, and Campylobacter jejuni, which is perhaps the 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. Resemblance of the triggering pathogens to antigens on peripheral nerves (ie, molecular mimicry) leads to an overzealous autoimmune response mounted by T-lymphocytes and macrophages.
This interaction then causes the acute demyelinating polyradiculoneuropathy or, particularly in cases involving C jejuni infection, an acute axonal degeneration. A variant of GBS, Miller Fisher syndrome, which is characterized by the triad of ophthalmoplegia, ataxia, and areflexia, is also linked to preceding infection with C jejuni. Most of these patients have antibodies against the GQ1b ganglioside.
The acute motor axonal neuropathy (AMAN) subtype of GBS is a purely motor disorder that is more prevalent amongst pediatric age groups. Nearly 70-75% of patients are seropositive for Campylobacter.
One third of patients with AMAN may actually be hyperreflexic. The mechanism for this hyperreflexia is unclear; however, dysfunction of the inhibitory system via spinal interneurons may increase motor neuron excitability. Hyperreflexia is significantly associated with the presence of anti-GM1 antibodies. Inflammation of the spinal anterior roots may lead to disruption of the blood-CNS barrier. AMAN is generally characterized by a rapidly progressive weakness, ensuing respiratory failure, and good recovery.
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 associated with C. jejuni.
Regarding the concern of antecedent vaccinations, the US Centers for Disease Control and Prevention (CDC) has published retrospective data of the 1000 reported cases of known GBS from 1990-2005. The highest number of GBS cases was observed after an influenza vaccination (n=632) and the second highest was after a hepatitis B vaccination (n=94).
Based on data obtained from the National Health Interview Survey from 1997-2005, an average of 54 million patients are vaccinated with the influenza vaccine each year. Thus, the incidence of postinfluenza vaccination GBS is approximately 0.75 per 1 million vaccinations. The adult and child total mortality of seasonal influenza alone in the United States is estimated to be more than 36,000 per year according to CDC so the risk of death from influenza alone would appear to far outweigh the risk of influenza vaccination-related GBS.
Preliminary surveillance results of GBS after 2009 H1N1 influenza vaccination up to March 2010 revealed an increased incidence of GBS of 0.8 cases per 1 million people in both adults and children, which is comparable to the rate seen with other seasonal influenza vaccines (1 extra case per 1 million vaccinations). This is in contrast to a death rate of 9.7 and hospitalization rate of 222 per 1 million population for H1N1-associated illness.
The World Health Organization (WHO) reported fewer than 10 cases of GBS out of 65 million people vaccinated against H1N1 in 2009. A case reported a pediatric patient developing GBS following immunization against H1N1 influenza.
A large Latin American study of more than 2000 children with GBS following a mass measles vaccination program in 1992-1993 failed to establish a statistically significant causal relationship between administration of the measles vaccine and GBS.
Post licensure surveillance of the quadrivalent human papillomavirus (qHPV) vaccine from 2006-2008 reported 12 confirmed cases of GBS resulting in a relative risk of GBS following qHPV vaccination of 0.3 per 100,000 person years, which is no higher than the rate expected in the general population. Of note, 3 cases of a rapidly progressive motor neuron disease have also been reported, although a causal relationship has not been established.
Review of the Menactra meningococcal conjugate vaccine (MCV) reveals a slight increase in the risk of GBS, with a rate of 0.20 cases of GBS per 100,000 person–months compared with a background incidence of 0.11 GBS cases per 100,000 person–months in unvaccinated individuals. But, similar to the data on influenza, the risk of meningococcal-related morbidity and mortality far outweighs the risk of vaccination-related GBS.
Case-cohort control analysis is needed to fully define the association of vaccines and GBS, especially in children, and to explore the risk factors of why some rare individuals may be most vulnerable to vaccine-related GBS.
United States statistics
Estimates of the annual incidence of GBS range from 0.5-1.5 cases per 100,000 population in individuals younger than 18 years. Only rarely does GBS occur in children under the age of 2 years. There is a slight male predominance. No clear seasonal preponderance of GBS has been noted in the United States although some seasonal variation is reported in neighboring Mexico and Central America.
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.
Epidemics of an illness closely resembling GBS 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 involved degeneration of peripheral motor axons without much inflammation, the syndrome has been termed acute motor axonal neuropathy (AMAN).
Other region-specific demographic studies have shown discrete preponderances 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.
An Indian case-control study reported that 27.7% of childhood GBS cases were associated with C jejuni infection. A study in Iran showed that 47% of pediatric GBS cases had evidence of recent C jejuni infection.
Since the disappearance of polio in 2000 in Bangladesh, a high incidence of acute flaccid weakness in Bangladeshi children (3.25 cases per 100,000) is still present but is now related mostly to GBS. Frequent exposure to enteric pathogens at an early age may increase this incidence of GBS.
Racial and sexual differences in incidence
Although major histocompatibility locus genes may play a role in susceptibility to GBS, no evidence exists for any racial predilection.
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 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.
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.
In Pakistan, a combined adult and pediatric GBS study (n=175) reported that 68% of all patients were male. In a study of 52 Indian children (median age, 5 y) with GBS, 75.4% were male. In a retrospective analysis of 10,486 cases of GBS in those younger than 15 years in Latin America and the Caribbean, 58.2% were male.
Age-related differences in incidence
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 cases 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.
Recent retrospective reviews of childhood GBS reported the average age to be in the range of 4-8 years. Delay in diagnosis in preschool children (< 6 y) may occur because preschool children usually appear with refusal to walk and pain in the legs, whereas older children (aged 6-18 y) present with more classic symptoms (weakness and paresthesias). This often leads to initial misdiagnosis in preschool children with myopathy, tonsillitis, meningitis, rheumatoid disorders, coxitis, or diskitis. Individuals affected with GBS can be as young as 3 weeks. One should keep GBS in the differential diagnosis when a floppy baby has no other evidence of hypotonia.
In general, the outcome of GBS is more favorable in children than in adults. Deaths are relatively rare, especially if the disorder is diagnosed and treated early. However, the recovery period is long, 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. 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.
Recurrence of GBS occurs in approximately 5% of cases, sometimes many years after the initial bout. Treatment-related fluctuation (deterioration after IVIG treatment) in one small series was 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). Time is currently the main divider between CIDP and AIDP in that CIDP can be diagnosed only if the patient has been symptomatic for 8 weeks or more.
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.
Family counseling and education is extremely important early in the illness. The family must be prepared for a prolonged and potentially complicated course of illness.
MayoClinic.com, Guillain-Barré syndrome
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