Current Management in Child Neurology, Third Edition© 2005 Bernard L. Maria, All Rights Reserved Guillain Barré SyndromeBC Decker Inc Pages 630–633

CHAPTER 94

GUILLAIN-BARRÉ SYNDROME

LESLIE A. MORRISON, MD

Since the eradication of poliovirus in the developed world,Guillain-Barré syndrome (GBS) is the most common causeof acute flaccid paralysis in childhood, affecting approxi-mately 1 in 100,000 children each year. The discovery ofseveral forms of similar but distinct immune-mediatedpolyneuropathies has expanded the term GBS to includeacute inflammatory demyelinating polyradiculoneuropa-thy (AIDP), Miller Fisher syndrome of ophthalmoparesis,areflexia and ataxia, acute motor axonal neuropathy(AMAN), acute motor and sensory axonal neuropathy(AMSAN), and acute sensory axonal neuropathy (ASAN).Nervous system involvement is peripheral, though cranialnerve involvement and myelopathy may coexist.

Fortunately, most children regain almost full motor func-tion. Even so, rapid pulmonary decline and complications ofintensive care result in mortality rates of 3 to 5%. Mechanicalventilation and prolonged hospitalization are noted inanother 20 to 25%, and relapse and residual disability areseen in approximately 5 to 20%. Axonal forms, more fre-quently seen in Asian and Latin American children, tend tohave more severe weakness and longer duration of illness.Beyond supportive care, treatment focused on modulation ofthe immune response can shorten the duration of disability,an important consideration in severely weak children.Deciding when and how to treat GBS depends on severity ofillness, availability of resources, and age of the child. Variousassessment scales have been used to determine severity and tomonitor improvements. Practice parameters are establishedin adults, but little class I evidence is available for children.

Clinical Course

An antecedent respiratory or gastrointestinal infection isreported in more than one-half of children, followed by

pain in the back or limbs, progressive symmetrical weak-ness, and areflexia. The degree of weakness varies widely,with some children showing only minor gait disturbanceand others developing complete paralysis requiring intu-bation within hours of presentation. Maximum weaknessis usually within 2 to 3 weeks of onset followed by a periodof stabilization and gradual improvement over days tomonths in a proximal to distal fashion. Relapsing orchronic forms lasting more than 2 months are termedchronic inflammatory demyelinating polyradiculoneu-ropathy (CIDP).

Pathogenesis

Evidence for an immune-mediated mechanism of injury tothe peripheral nervous system is mounting. There areknown antibodies to gangliosides and other proteins foundin peripheral nerve axons and myelin associated with GBS.Immunoglobulin G antibodies to GQ1b are found in a highpercentage of patients with Miller Fisher syndrome, andGD1a and GD1b in AMAN. In some regions, strong asso-ciations with Campylobacter jejuni infections are found inMiller Fisher syndrome and AMAN. Campylobacter has theability to stimulate the formation of antibodies to gan-gliosides found in GBS. These findings support the conceptof molecular mimicry after viral or bacterial infection andthe subsequent development of an immune-mediatedpostinfectious disease. A recent paper described a study ofhuman leukocyte antigens (HLA) class II antigens inChinese children; associations were found in those withAIDP but not in those with AMAN. This suggests differ-ent immune mechanisms in these two variants. In animalmodels, these and other antibodies seem to elicit a T-cellmediated response to peripheral myelin or axonal compo-

As the most common cause of acute flaccid paralysis, Guillain-Barré syndrome is important to recognize and diagnose. Propermonitoring and appropriate management can be lifesaving.

Guillain-Barré Syndrome / 631

nents. An immune attack is supported in pathologicalstudies of nerve fibers in humans and animals with specificregions on axons or myelin involved that correspond withelectrophysiologic findings. Increased relative risk of devel-opment of GBS after immunizations seems small, with theexception of the swine influenza vaccine given in1976/1977.

Diagnosis

Diagnosis can be confirmed through history, physicalexamination, electrodiagnostic studies, and lumbar punc-ture. Abnormalities on electrodiagnostic studies evolveover the first 2 weeks and differ between AIDP and AMAN(Table 94-1). After the first days, cerebrospinal fluid (CSF)typically shows albuminocytologic dissociation with fewerthan 10 to 50 leukocytes, along with an elevated protein.Stool can be cultured for Campylobacter, with highest asso-ciations in Miller Fisher syndrome and AMAN. The clin-ical utility of specific antibody tests is not yet established,but they may have prognostic significance. Magnetic res-onance imaging (MRI) of the spinal cord with gadoliniumshows anterior nerve root enhancement but is of little diag-nostic use unless other diagnostic studies are equivocal orwhen myelopathy is suspected.

Differential Diagnosis

West Nile virus infection can present with acute flaccidparalysis, a nonpoliovirus poliomyelitis. There is a well-documented report of inflammatory demyelinatingpolyneuropathy in an adult patient with West Nile infec-tion. Enterovirus 71 can cause brainstem encephalitis thatmay resemble Miller Fisher syndrome or an acute flaccidparalysis in infants and young children. Children are likelyto be febrile, and spinal fluid may show pleocytosis in bothconditions. Rapid onset of weakness in spinal muscularatrophy (SMA) may mimic GBS even in the neonatalperiod, and vice versa. In most cases, SMA can be excludedby electrophysiologic studies and deoxyribonucleic acid

(DNA) analysis. Treatable infections such as herpesvirusmyelitis or mycoplasma-associated weakness should not bemissed, and cases of human immunodeficiency virus(HIV)- and hepatitis-associated GBS have been reported.Botulism should be considered in infants, as botulismimmunoglobulin can reduce duration of critical care.Myasthenia should be considered when ophthalmoplegiaand bulbar signs are present. Acute transverse myelitis withacute areflexia and urinary retention mimics GBS, espe-cially in young children where a sensory level may be dif-ficult to discern. Toxic neuropathies should be excluded onthe basis of history, with specific inquiry with regard toexcessive intake of vitamins and food supplements.Metabolic diseases such as disorders of oxidative phos-phorylation and porphyria can mimic postinfectiouspolyneuropathy. Thorough examination, especially alongthe hairline, excludes tick paralysis. History and examina-tion can help exclude other envenomations.

In the critical care setting, paralysis after lightening ofsedation should raise the question of critical illness polyneu-ropathy or myopathy. Analysis of creatine kinase and elec-trophysiologic evaluation may be useful in cases with min-imal or no improvement. Children with hereditary motorand sensory neuropathy are at increased risk of developinga secondary immune-mediated acute worsening.

Treatment

Children should be hospitalized for observation with closemonitoring of respiratory, autonomic, and motor functionuntil they have stabilized. Declining respiratory functionand autonomic instability warrant intensive care admis-sion. Negative inspiratory force can be followed in olderchildren, but infants and young children require a morecreative approach, such as counting, blowing a pinwheel,or pretending to blow out a candle. Pulse oximetry is notalways a reliable predictor of impending respiratory failure.Autonomic instability, manifested by rapid swings in bloodpressure, pulse, cardiac arrhythmias, urinary retention,and pupillary abnormalities, must be closely monitored.Rapid treatment responses may be necessary to managepotential life-threatening fluctuations of blood pressure,pulse, and cardiac rhythms.

Specific treatment of GBS depends on respiratory andautonomic involvement and the degree of weakness. Mostclinicians would advise treatment in nonambulatory chil-dren and those with respiratory compromise and woulddefer specific treatment in cases where symptoms are mildand stable or improving (Table 94-2).

Corticosteroids are ineffective in GBS. Based on infer-ence from class I studies in adults and small pediatric caseseries, the safety and efficacy of intravenous immunoglob-ulin (IVIg) and plasma exchange (PE) are established. The

Current Management in Child Neurology, Third Edition© 2005 Bernard L. Maria, All Rights Reserved Guillain Barré SyndromeBC Decker Inc Pages 630–633

TABLE 94-1. Electrophysiologic Findings in Guillain-BarréSyndrome

AIDP AMAN

Reduced conduction velocities Diminished CMAP amplitudesProlonged distal and F-wave Preserved motor nerve conduction

latencies velocitiesAbnormal temporal dispersion Denervation on EMG

Normal sensory conduction studies

AIDP = acute inflammatory demyelinating polyradiculoneuropathy; AMAN =acute motor axonal neuropathy; CMAP = compound muscle action potential;EMG = electromyogram.

632 / The Hospitalized Child

duration of disability is shortened by either of these twotreatments in AIDP and AMAN but their effectiveness isless clear in AMSAN and often they are not necessary inASAN. Differences in overall outcome in subtypes withand without treatment have not been established. Thechild’s age and size are important factors, as PE requires asecure intravenous catheter of relatively large bore. Mostauthors recommend 5 to 7 treatments (measured inplasma volumes) given daily or every other day, depend-ing on severity of weakness and tolerance of the procedure.In patients with renal failure, PE may be preferable to IVIg.

In most cases, treatment with IVIg is selected on thebasis of equal efficacy, safety, and ease of administration.Early concerns over increased risk of relapse have largelyabated. Empiric dosage is a total of 2 g/kg given over 1 to5 days. No controlled studies prove superiority of a par-ticular dosing schedule in GBS, but most authorities rec-ommend that the infusion rate not exceed 0.08 mg/kg/min.Children appear to tolerate more rapid infusion rates thanadults, and many centers infuse over 1 or 2 days. Decisionsare often made on the basis of tolerance, monitoringrequirements, and clinical severity and stability.

IVIg is manufactured from pooled human plasma from3,000 to 10,000 donors that have been screened for HIV,human T-lymphotropic virus type I, and hepatitis A, B,and C. It is purified and mixed with stabilizer sugars oramino acids. CD4, CD8, human leukocyte antigens,cytokines, and coagulation factors may be present in thefinal product. IVIg has a half-life of 18 to 32 days, sorepeated treatment courses seem unnecessary unless thereis relapse. Side effects of IVIg treatment include infusion-related headache, fever, nausea, and rash. These are man-aged by slowing the infusion rate or by pretreatment withacetaminophen, antihistamines, or corticosteroids.Because the pooled product can contain up to 2.5%immunoglobulin A (IgA), there is risk of serious allergicreaction in IgA-deficient patients; therefore, animmunoglobulin panel is recommended before treatment.Renal failure may be averted through careful hydrationand by avoiding high-sucrose–containing preparations.

Concern over risk of hepatitis has diminished since theaddition of detergents that inactivate this and most otherinfectious particles, with the exception of prions, aboutwhich there is insufficient information.

Combined treatment with both IVIg and PE does notimprove outcome; however, when the first treatment failsto be effective in severe, refractory cases, the alternatetreatment might be offered. In this scenario, controversypersists as to which treatment to give first. CSF filtrationwas compared with PE in a small study of 37 adult subjects,showing equal efficacy. This treatment is not available inmost centers and is unlikely to become widely used becauseof potential serious infectious complications. A recentstudy of 19 patients treated with interferon IFNb-1a orplacebo in addition to IVIg showed no significant differ-ence in rate of improvement.

Pain management should be timed before physicalmaneuvers and therapy and may be severe enough towarrant narcotics. Dysesthesias are more likely torespond to gabapentin.

Finally, rehabilitation should begin very early.Prevention of deep venous thrombosis is aided by range ofmotion and intermittent compression devices. Heel cordcontractures can develop within days of onset, requiringrange of motion exercises, and splinting or casting.Supervised sitting and standing should begin once thechild is able to do so. Respiratory therapy is provided toreduce atelectasis and mobilize secretions. The illness mayhave long-lasting psychological effects on children, andattention to mental health is essential for good outcome.The child and family will need ongoing education andemotional support, particularly when the treatment doesnot appear effective and the child is on a ventilator. Ameans of communication with simple measures, such aschalkboard or paper, or with more highly technical devicesis important. Selection is made on the basis of duration ofventilation, degree of hand function, and age of the child.

Treatment of CIDP includes corticosteroids, PE, andIVIg, as well as continued supportive measures and reha-bilitation. Immunosuppressive therapies may be required.

Current Management in Child Neurology, Third Edition© 2005 Bernard L. Maria, All Rights Reserved Guillain Barré SyndromeBC Decker Inc Pages 630–633

TABLE 94-2. Treatment of Guillain-Barré Syndrome

Treatment Administration Mild Side Effects Serious Side Effects

IVIg: 2 g/kg total dose Single dose, slow IV infusion, or Headache, myalgia, fever, chills, rash; Congestive heart failure, thromboembolic divided over 2–5 d; start within may pretreat with acetaminophen, events, renal failure, anaphylaxis, and 2 wk of symptoms diphenhydramine, or corticosteroids; aseptic meningitis; prescreen for

slow infusion rate IgA deficiency and clotting disorders

PE: approximately one 5–7 separate exchanges over 1–2 wk; Less likely to complete course but may Hypotension, cardiac arrhythmias, sepsis, plasma volume per start within 4 wk of symptoms be preferable in renal failure thrombosis, hemorrhage, and increasedtreatment risk of IV infections

IgA = immunoglobulin A; IV = intravenous; IVIg = intravenous immunoglobulin; PE = plasma exchange.

Current Management in Child Neurology, Third Edition© 2005 Bernard L. Maria, All Rights Reserved Guillain Barré SyndromeBC Decker Inc Pages 630–633

Guillain-Barré Syndrome / 633

Griffin JW, Sheikh K, Li CY. Acute motor axonal neuropathy. In:Jones HR, DeVivo DC, Darras BT, editors. Neuromusculardisorders of infancy, childhood, and adolescence: a clinician’sapproach. Philadelphia (PA): Butterworth Heinemann; 2003.

Hughes RAC, Wijdicks EFM, Barohn R, et al. Practice parameter:immunotherapy for Guillain-Barré syndrome. Neurology2003;61:736–40.

Ropper AH. The Guillain-Barré syndrome. N Engl J Med1992;326:1130–6.

Sladky JT. Guillain-Barre syndrome. In: Jones HR, DeVivo DC,Darras BT, editors. Neuromuscular disorders of infancy,childhood, and adolescence: a clinician’s approach.Philadelphia (PA): Butterworth Heinemann; 2003.

van der Meché FGA, Schmitz PIM, Dutch Guillain-Barré StudyGroup. A randomized trial comparing intravenousimmunoglobulin and plasma exchange in Guillain-Barrésyndrome. N Engl J Med 1992;326:1123–8.

Practitioner and Patient Resources

Guillain-Barré Syndrome International http://www.guillain-barre.com Patient support in English and Spanish.

Outcome

Outcome is generally good in GBS. Most children withAIDP regain full function. Initially, children withAMAN were believed to have a worse prognosis, butnew information supports good recovery in these chil-dren as well. Risk factors for residual weakness includerapidity of onset, severity of paralysis, respiratory orinfectious complications, or diagnosis of AMSAN.Relapse occurs in a small percentage of children. Thereis a low risk of relapse or recurrence after immuniza-tions, but one author has advised waiting one yearbefore immunizations and avoiding any immunizationgiven within 12 weeks of onset.

Suggested Readings

Brannagan TH. Intravenous gammaglobulin (IVIg) for treat-ment of CIDP and related immune-mediated neuropathies.Neurology 2002;59:S33–40.

Griffin JW, Li CY, Ho TW. Guillain-Barré syndrome in northernChina. The spectrum of neuropathological changes in clin-ically defined cases. Brain 1995;118:577–95.