Pediatric Guillain-Barre Syndrome

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.[1]

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.[2]

Go to Guillain-Barre Syndrome and Emergent Management of Guillain-Barre Syndrome for complete information on these topics.

Demyelinating and axonal forms of Guillain-Barré syndrome (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.[3] Inflammation of the spinal anterior roots may lead to disruption of the blood-CNS barrier.[4] AMAN is generally characterized by a rapidly progressive weakness, ensuing respiratory failure, and good recovery.

Guillain-Barré syndrome (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.

Vaccinations

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).[5]

Based on data obtained from the National Health Interview Survey 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[6] 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.[7]

The World Health Organization (WHO) reported fewer than 10 cases of GBS out of 65 million people vaccinated against H1N1 in 2009.[8] A case reported a pediatric patient developing GBS following immunization against H1N1 influenza.[9]

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.[10]

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.[11] Of note, 3 cases of a rapidly progressive motor neuron disease have also been reported, although a causal relationship has not been established.[11]

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.[12] 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.

In French Polynesia 42 patients with Zika virus (ZIKV) were found to have GBS. This marks an increase from 5 cases detected annually in the past 4 years. From April 2015 to 2016 electrode to low 164,237 conformer and suspected cases of ZIKV disease, and 1474 cases of GBS were reported in Bahai, Brazil, Colombia, Dominican Republic, El Salvador, Honduras, Surinam, and Venezuela. The incidence of GBS during the period of the Zika wire circulation increased with age for males and females with males older than 60 years  having the highest rate of GBS. There was no report for the pediatric age group.[13]

United States statistics

Estimates of the annual incidence of Guillain-Barré syndrome (GBS) range from 0.5 to 1.5 cases per 100,000 population in individuals younger than 18 years. Only rarely does GBS occur in children younger than 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.[14]

In the United States, only 8 cases of GBS have been reported. There are 43 locally acquired mosquitoborne cases of Zika virus and 3358 travel-related cases reported.[15]

International statistics

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.[16] 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).[17]

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 to September, unlike AIDP, which seemed to be more evenly distributed throughout the year.[18]

An Indian case-control study reported that 27.7% of childhood GBS cases were associated with C jejuni infection.[19] A study in Iran showed that 47% of pediatric GBS cases had evidence of recent C jejuni infection.[20]

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.[21]

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.[22]

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.[18]

In Pakistan, a combined adult and pediatric GBS study (n=175) reported that 68% of all patients were male.[23] In a study of 52 Indian children (median age, 5 y) with GBS, 75.4% were male.[24] 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.[14]

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.[25] 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.[26]

In general, the outcome of Guillain-Barré syndrome (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.

For patient education information, see the Brain and Nervous System Center, as well as Guillain-Barré Syndrome. Other patient and family-oriented Web sites include the following:

• NINDS Guillain-Barré Syndrome Information Page

• GBS/CIDP Foundation International

• MayoClinic.com, Guillain-Barré syndrome

Patients with Guillain-Barré syndrome (GBS) present with complaints of weakness and/or unsteadiness (ataxia). Weakness is a hallmark of GBS. The weakness typically starts in the legs and ascends to the arms (hence, the description progressive ascending flaccid paralysis). This progression may occur over hours to days to weeks. The weakness is usually symmetric.

Pain and dysesthesias also are noted, particularly in children. Pain may be the initial manifestation in almost half of affected children. The nonspecific nature of the symptoms may distract from the actual diagnosis, for exampe, a pediatric patient presenting with prolonged and unexplained abdominal pain.

Often, onset of these symptoms is within 2–4 weeks of an illness or immunization. The preceding illness often involves fever, muscle pains, diarrhea or upper respiratory infection.

Urinary retention is also noted early in the course of 10–15% of children with GBS. At the peak of illness, about half the pediatric patients with GBS may have associated autonomic dysfunction and cranial nerve (CN) involvement, and about 10–12% require a mechanical ventilator. In those with CN involvement, the facial nerve is most commonly affected, resulting in bilateral facial weakness.

Subtypes of GBS

GBS peripheral nerve damage can be classified histopathologically into 2 main types: demyelinating forms and axonal-degenerating forms. Motor nerves are more susceptible to disease than sensory ones. In 1995, GBS was subdivided into 4 distinct forms based on histopathological and neurophysiological basis: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller-Fisher syndrome (MFS).[27, 28]

The clinical spectrum of GBS, which includes individual variation and variable severity of presentation, comprises the following:

• Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) - This accounts for 80–90% of GBS cases in Europe and North America. It is characterized by an immune-mediated attack on myelin with infiltration of lymphocytes and macrophages with segmental stripping of myelin. Motor and sensory fibers are usually affected simultaneously, producing corresponding deficits. Electrophysiology shows slow nerve conduction velocity and prolonged F waves.

• Acute motor axonal neuropathy (AMAN) - This form of neuropathy is most commonly seen in China and Japan (50-60% of cases), as apposed to Western countries (10–20% of cases). In this form, axonal degeneration occurs by immune attack within 1–2 weeks after infection. Specific antibodies to axonal membranes of motor fibers attack the nodes of Ranvier. This, in turn, activates complement and intrusion of macrophages into periaxonal space, resulting in destruction of axons. C jejuni is the most common preceding infection, and antiganglioside antibodies are usually found in this type. Electrophysiology shows reduction in muscle action potentials with relatively preserved motor nerve conduction velocity and normal sensory nerve action potentials and F waves.[27, 29]

• Acute motor and sensory axonal neuropathy (AMSAN) - This type is rare and resembles AMAN except sensory nerves are also affected. This type is associated with a severe course and poor prognosis.

• Miller-Fisher syndrome (MFS) - The involvement of CNs is very distinct in this form of GBS. Ocular motor nerves (oculomotor, trochlear, and abducens) are affected and produce a triad of ophthalmoplegia, ataxia, and areflexia. Electrophysiology is normal. The characteristic autoantibodies are against gangliosides GQ1b and GT1a. GQ1b plays a key role in the pathogenesis of MFS.[29]

• Polyneuritis cranialis - This is an acute onset of multiple CN palsies (usually bilateral CN VII with sparing of CNs I and II), elevated cerebrospinal fluid protein, and slowed nerve conduction velocity with uncomplicated recovery.

• Pharyngo-cervical-brachial syndrome - This variant form of GBS is characterized by localized and regional involvement of autonomic and motor nerves in the pharyngeal-cervical-brachial distribution. The diagnosis of this condition is based on clinical, laboratory, and neurophysiological findings and the exclusion of other conditions mimicking this disorder.

• Acute sensory neuropathy of childhood

• Acute pandysautonomia - Besides the above main forms of GBS, acute pandysautonomia is also a common subtype with which the autonomic nervous system is involved. Parasympathetic and sympathetic involvement is seen along with sensory or motor nerve involvement.

On physical examination, an ascending motor weakness is noted along with areflexia in the classic form. Areflexia is a hallmark of Guillain-Barré syndrome 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.

Occasionally, autonomic instability (26%), ataxia (23%), dysesthesias (20%), and cranial nerve findings (35–50%), predominantly facial palsy, are noted.[30] 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.

The autonomic neuropathy involves both the sympathetic and parasympathetic systems. Manifestations include orthostatic hypotension, hypertension, pupillary dysfunction, sweating abnormalities, and sinus tachycardia.

The clinical features of pediatric GBS differ from those of adult GBS. Pain is a more frequent complaint in children, in short intervals from disease onset to fulminant, and there is a higher incidence of bulbar dysfunction, which is a risk factor for mechanical ventilation in children. It is also very distinct from adult autonomic dysfunction, which is significantly higher in mechanically ventilated children with GBS. Disease severity in pediatric patients is the same as in adult patients.[31]

Complications of GBS

The most common serious complications are weakness of the respiratory muscles and autonomic instability. Pneumonia, adult respiratory distress syndrome, septicemia, pressure sores, pulmonary embolus, ileus, constipation, gastritis and dysesthesias are also important potential complications. Nephropathy has been reported in pediatric patients.[32]

Features that would put the diagnosis in doubt include (1) marked persistent weakness, (2) bowel and bladder dysfunction at onset, (3) persistent bladder or bowel dysfunction, (4) mononuclear leukocytosis in the cerebrospinal fluid (>50 cells/µL), and (5) a sharp sensory level

Features that rule out the diagnosis include (1) a current history of hexacarbon abuse; (2) abnormal porphyria metabolism; (3) recent diphtheria infection; and (4) evidence of polio, botulism, toxic neuropathy, tic paralysis, or organophosphate poisoning.

Features required for diagnosis are (1) progressive weakness of more than one extremity, (2) hyporeflexia or areflexia, (3) elevated cerebrospinal fluid protein (>45 mg/dL) after 1 week following onset of symptoms, and (4) slow conduction velocity or prolonged F wave on electrophysiology testing.

The diagnosis of Guillain-Barré syndrome (GBS) is typically based on the presence of a progressive ascending weakness with areflexia.

Findings on lumbar puncture, electrodiagnostic studies, or occasionally MRI can give support for the diagnosis. However, abnormalities on these studies do not develop until days to weeks after onset of symptoms.

Nearly 2 weeks after presentation of symptoms, lumbosacral MRI can show enhancement of the nerve roots with gadolinium. This imaging study has been described to be 83% sensitive for acute GBS, with nerve root enhancement present in 95% of typical cases.[35]

Typically, the LP findings are suggestive of demyelination (ie, increased protein >45 mg/dL within 3 weeks of onset) without evidence of active infection (lack of CSF pleocytosis), as originally noted by Guillain, Barré, and Strohl. The CSF findings may be normal within the first 48 hours of symptoms, and occasionally the protein may not rise for a week. Usually by 10 days of symptoms, elevated CSF protein findings will be most prominent.

Most patients have fewer than 10 leukocytes per milliliter, but occasionally a mild elevation (ie, 10-50 cells/mL) is seen. Greater than 50 mononuclear cells/mL of CSF makes the diagnosis of GBS doubtful.

Within the first week of the onset of symptoms, electrodiagnostic studies in at least two limbs reveal the following:

• A dispersed, impersistent, prolonged, or absent F response (88%)

• Increased distal latencies (75%)

• Conduction block (58%) or temporal dispersion of compound muscle action potential (CMAP)

• Reduced conduction velocity (50%) of motor and sensory nerves

Criteria for axonal forms include lack of neurophysiologic evidence of demyelination, with loss of amplitude of CMAP or sensory nerve action potentials to at least less than 80% of lower limit of normal values for age. It is typically prudent to wait at least 7-10 days for electrical studies to be informative. If electrical studies are performed too early, normal results can be falsely reassuring.

By the second week of illness, reduced compound muscle action potential (CMAP, 100%), prolonged distal latencies (92%), and reduced motor conduction velocities (84%) are prominent.

In adults with GBS, serum ganglioside antibodies directed against GM1, GM1b, GD1a, and GalNAc-GDIa have been associated with Campylobacter jejuni infection, acute motor axonal neuropathy, a more severe course, and more residual neurologic deficits. The value of these studies as a prognostic marker in children is still under evaluation.

A study of 32 Japanese children diagnosed with GBS identified one or more of these antibodies in 44% and in 64% of those who met the electrodiagnostic criteria for acute motor axonal neuropathy. Those with positive antibodies had a more prolonged recovery with more residual symptoms at the end of the study.[36] However, another study in Western Europe did not find any difference in clinical course or outcome in the 4 patients with positive antibodies out of 63 total children with GBS.[37]

Other antibodies are associated with specific forms of GBS, such as GQ1b with Miller-Fisher syndrome, GD1b with acute sensory neuronopathy, and GT1a with pharyngeal-cervical-brachial variant. Assays for these antibodies may be useful in the diagnostic workup of variant clinical presentations.

Although not typically part of routine GBS diagnostic evaluation in pediatric or adult patients, the following are expected findings in GBS:

• In the demyelinating form, demyelination and mononuclear infiltration by lymphocytes and macrophages are seen in peripheral nerves

• Lymphocytes and macrophages surround endoneural vessels and cause an adjacent demyelination

• These lesions can be discrete and are scattered throughout the peripheral nervous system, although they may have a predilection for inflammation of the nerve roots.

• The conduction block and demyelination of the motor nerves result in the progressive weakness that is characteristic of this syndrome. Similarly, the involvement of the sensory nerves leads to pain and paresthesias

Many authors believe that the mechanism of the disease involves an abnormal T-cell response precipitated by a preceding infection. This is thought to give rise to an abnormal immune stimulation. A variety of specific endogenous antigens may be involved in this response, including myelin P-2 and ganglioside GM1, GQ1b, and GT1a.

In this axonal form of GBS, biopsy specimens reveal wallerian like degeneration of fibers in the ventral and dorsal nerve roots, with only minimal demyelination or lymphocytic infiltration. These axonal lesions affect both the sensory fibers and the motor fibers.

Although this form of GBS has been associated with Campylobacter infection, it appears to be a rare complication of such infection.

To date, treatment for Guillain-Barré syndrome (GBS) has been aimed primarily at immunomodulation.[38]

In pediatrics, the most effective form of therapy is intravenous immunoglobulin (IVIG). Each batch of IVIG is made of human plasma derived from pools of 3,000–10,000 donors. Plasmapheresis may also be used.

Corticosteroids were previously used to treat GBS, but current data indicate they provide little benefit.

Go to Guillain-Barre Syndrome and Emergent Management of Guillain-Barre Syndrome for complete information on these topics.

IVIG has been shown to be safe and effective in the treatment of pediatric Guillain-Barré syndrome (GBS).[39, 40] Although only one prospective, randomized treatment trial in childhood GBS has been published,[41] multiple studies have shown that IVIG seems helpful in reducing the severity of the disease as well as the duration of symptoms. However, the long-term outcome may not be affected.

Several regimens have been used. The optimal dose and dosage schedules for IVIG have not been rigorously determined in childhood GBS. One possible regimen includes daily administration of IVIG for 5 days at a dose of 0.4 g/kg/d, which can lead to improvements 2-3 days after the start of therapy. IVIG can be given by way of a peripheral intravenous route.

Some authors use 2 g/kg of IVIG given as a single dose or 1 g/kg/d over 2 days in children who are showing rapid signs of deterioration. Although, in a small, randomized trial, the outcomes between the 2 treatment regimens were equivalent, treatment-related fluctuation (deterioration after receiving IVIG) occurred more often in children who received the 2-day course of IVIG.[41]

Studies in children using both historical and case controls indicate that plasmapheresis may decrease the severity and shorten the duration of Guillain-Barré syndrome (GBS). Between 4 and 5 plasmapheresis treatments may be performed over 7–10 days, as described in standard protocols. Potential complications include autonomic instability, hypercalcemia, and bleeding due to depletion of clotting factors.

Results of plasmapheresis and IVIG are similar, with possibly fewer side effects seen with IVIG. It stands to reason that plasmapheresis should not typically follow IVIG administration.

The availability of plasmapheresis is generally limited to major referral centers that have the requisite equipment and trained personnel. Central line vascular access dictates intensive care hospitalization. In addition, plasmapheresis is limited to larger children; in most institutions, children weighing less than 10–15 kg may not be considered for volume exchange therapy. These features distinguish plasmapheresis from IVIG, which can be given to smaller children and can be administered via peripheral IV in specialized ambulatory clinic settings, advanced home nursing programs, and at ward level hospital settings.

When high cost limits the use of IVIG or unavailability limits the use of plasmapheresis, exchange transfusion can be used as an alternative therapy for severe Guillain-Barré syndrome disease in children.

Careful attention should be paid to multiple issues that may require intervention and specialist consultation. Temperature, blood pressure, heart rate, respiratory capacity, and urine output of the patient should be monitored. In pediatric patients, monitoring for dysautonomia is paramount.

Among the concerns of Guillain-Barré syndrome (GBS) comorbidities are cardiorespiratory function, nutrition, urinary retention, decubitus ulcers, constipation, gastritis, dysesthesias/pain, mood and anxiety issues, iatrogenic infectious complications, and contractures in patients who are severely ill or who have a particularly prolonged course.

During the acute phase of the illness, orthostatic hypotension and urinary retention also may cause significant problems. In addition to the weakness, autonomic symptoms (eg, orthostatic hypotension) may also restrict activity and should be monitored.

Respiratory status and signs of dysautonomia

During the acute phase of the disease, close attention should be paid to respiratory status and signs of dysautonomia. Intubation and mechanical ventilation should be considered when vital capacity falls below 15 mL/kg body weight or arterial pressure of oxygen falls below 70 mm Hg (or the patient has significant fatigue).

In cooperative children older than 5 years, respiratory function measurements, such as vital capacity or maximal inspiratory force (MIF), can be valuable. MIFs are also known as negative inspiratory force (NIF). MIFs are normally greater than -40 mL water pressure; thus, the more negative, the better MIF. MIFs less than -20 mL water pressure can be an indication of poor inspiratory ability and respiratory distress.

MIFs provide objective data to follow and compare. This measure is unfortunately difficult to monitor in young children (< 5 y) and in uncooperative children. Experienced pediatric respiratory therapists can be very valuable in these measures.

Experienced pulmonary care is vital if neuromuscular weakness is affecting pulmonary function. Possible interventions include continuous positive airway pressure (CPAP), bilateral positive airway pressure (BiPAP), mechanical ventilation, or cough-assist devices.

Blood gases are not helpful in assessing neuromuscular respiratory failure, as they do not become abnormal until there is no longer any respiratory reserve. Other means of assessing respiratory function, such as respiratory rate and dyspnea on lying supine, are far more valuable early indictors of respiratory dysfunction.

Chest radiographs can be obtained to look for signs of infection. Cardiac monitoring is essential to detect any signs of cardiovascular instability and treat any arrhythmia.

Consultation with a pediatric neurologist should be considered to confirm the diagnosis of Guillain-Barré syndrome. Intensivists may need to be involved quickly if critical care (cardiorespiratory) issues are suspected.

Once the patient’s condition has stabilized, patients should benefit from consultation with a rehabilitation medicine specialist, especially if it appears that recovery will be prolonged. Physical therapy, occupational therapy, and orthotics are also helpful.

Currently, management of Guillain-Barré syndrome (GBS) is not dependent on preceding infection. Some preceding infections are related to specific clinical variants or subtypes. These could be important factors in management, prediction of clinical course, and treatment in the future.

There have been trials to evaluate safety and efficacy of eculizumab-complement 5 factor inhibitor in adults, but none that studied effects in children.

In a Japanese study of eligible GBS patients who were unable to walk independently, patients were assigned to receive 4 weeks IVIG plus either eculizumab 900 mg or placebo. At 4 weeks, 61% of patients in the eculizumab group were able to walk compared with 45% in the placebo group. Two patients in the eculizumab group experienced adverse effects (intracranial hemorrhage and abscess).

This was a very small study without any statistical comparison with illicit drug growth. The efficacy and safety of eculizumab should continue to be investigated in larger randomized controlled trials.[42]

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Intravenous immunoglobulin (IVIG) is the predominant choice in childhood Guillain-Barré syndrome (GBS). DVT prophylaxis should be initiated and stress gastritis prophylaxis with H2 blockers (eg, ranitidine) may be beneficial. A bowel routine should also be instituted, as gastroparesis secondary to autonomic dysfunction and/or extended bed rest is not uncommon.

Class Summary

IVIG is an effective treatment of autoimmune neuropathies in general. It can reduce duration of hospitalization as well as need or duration for mechanical ventilation.

IVIG (Gammagard, Gamimune)

Features relevant to efficacy may include neutralization of circulating myelin antibodies through anti-idiotypic antibodies; down-regulation of proinflammatory cytokines, including interferon-gamma; blockade of Fc receptors on macrophages; suppression of inducer T and B cells and augmentation of suppressor T cells; blockade of complement cascade; promotion of remyelination; and a 10% increase in CSF IgG.

Class Summary

H2-receptor antagonists are reversible competitive blockers of histamines at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.

Cimetidine (Tagamet)

Cimetidine inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Ranitidine (Zantac)

Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Famotidine (Pepcid)

Famotidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Nizatidine (Axid)

Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.