Introduction. Clinical manifestations. Overview

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1 Guillain-Barre syndrome in children David T Hsieh MD ( Dr. Hsieh of the Uniformed Services University of the Health Sciences and The University of Texas Health Science Center at San Antonio has no relevant financial relationships to disclose. ) Bernard L Maria MD, editor. ( Dr. Maria of Thomas Jefferson University has no relevant financial relationships to disclose.) Originally released November 15, 1999; last updated October 11, 2017; expires October 11, 2020 Introduction Overview Guillain-Barré syndrome is an acquired, autoimmune-mediated radiculopolyneuropathy characterized by an ascending progressive motor weakness and areflexia. Sensory, autonomic, and brainstem findings can also occur. In this article, the author provides updates on the association of mycoplasma pneumonia with Guillain-Barre syndrome. Key points Guillain-Barré syndrome is an acquired, autoimmune-mediated radiculopolyneuropathy characterized by an ascending progressive motor weakness and areflexia. Although weakness is the hallmark symptom, differing presentations in children, as opposed to adults, can include predominant symptoms of gait ataxia or pain, and a higher incidence of cranial nerve abnormalities. Regional differences in presentation are observed, with demyelinating subtypes more prevalent in Western countries, such as the United States, and axonal subtypes more prevalent in Asia and in Mexico. The most significant complication is the need for respiratory support, which is reported in 10% to 28% of children. Historical note and terminology Guillain-Barré syndrome is an acquired, autoimmune-mediated radiculopolyneuropathy characterized by an ascending progressive motor weakness and areflexia. Sensory, autonomic, and brainstem findings can also occur. This syndrome was first described by Landry in 1859, later by the French army neurologists Guillain and Barré in 1916 (Ropper 1992). The observation by Guillain and Barré that this weakness occurred with "albuminocytologic dissociation" (ie, an elevated CSF protein with a normal CSF cell count) allowed this entity to be distinguished from polio and other neuropathies. Clinical manifestations Presentation and course The clinical manifestations of Guillain-Barré syndrome in children are often anteceded within 2 to 4 weeks by recent illness or immunization. An antecedent infection is reported in 75% of children with Guillain-Barré (Delanoe et al 1998; Hicks et al 2010). The hallmark of Guillain-Barré syndrome is an ascending weakness. Older, more verbal children and adults will present with complaints of weakness and unsteadiness. The weakness typically starts in the lower extremities and ascends into the upper extremities. This progression may extend from hours to days to weeks. In younger, less verbal children, the symptom of gait unsteadiness may be the initial presenting symptom, and an apparent gait ataxia is a clinical presentation that is distinct to childhood Guillain-Barré syndrome. In preschool-aged children (younger than 6 years of age), refusal to walk, with or without leg pain, is the most frequent presenting symptom, occurring in 65% (Roodbol et al 2011). Although weakness is the most common clinical feature, the most frequent initial presenting complaint in children is pain. Pain was the initial presenting complaint in 47% in a series (Delanoe et al 1998), and is reported during the clinical course in 55% to 67% of cases in children (Bradshaw and Jones 1992; Sladky 2004). Pain complaints mainly consist of headaches or muscular pain of the back and legs and can sometimes be severe in nature. This accentuates a pertinent feature of childhood Guillain-Barré syndrome: when severe pain is manifested in younger children who are

2 unable to verbalize or tolerate the pain, it often confounds the underlying diagnosis (Jones 2000) and can result in unnecessary referrals to other subspecialists, such as orthopedic surgeons (Matsushita et al 2013). Specifically, in preschool-aged children, this prominent symptom of pain contributes to misdiagnosis. Misdiagnosis occurred in two thirds of preschool-aged children in a series, resulting in a delay until correct diagnosis of more than 1 week in one fourth (Roodbol et al 2011). Sensory symptoms and paresthesias have been noted in 18% to 54% of children (Bradshaw and Jones 1992; Sladky 2004); it should be noted, though, that sensory symptoms are often difficult to elicit from younger, less verbal children. These sensory symptoms occur most commonly in the distal extremities (Bradshaw and Jones 1992). On physical examination, an ascending motor weakness is noted with areflexia. This weakness tends to be symmetric and usually begins in the legs. Ataxia has been reported in almost half of the children with Guillain-Barré syndrome (Sladky 2004). Cranial neuropathies are also a common finding, seen in 15% to 69% of these children (Bradshaw and Jones 1992; Delanoe et al 1998; Sladky 2004; Hicks et al 2010). The most common cranial neuropathy is of the facial nerve, seen in 33%, but ophthalmoplegia (16% to 21%) is also frequently reported (Bradshaw and Jones 1992; Delanoe et al 1998). Although areflexia or significantly diminished deep tendon reflexes is nearly universally present, there are rare cases reported of hyperreflexia (Tosun et al 2015). An autonomic neuropathy involving both the sympathetic and parasympathetic systems is also frequently seen, reported in 18% to 46% of children with Guillain-Barré syndrome (Jones and Bradshaw 1992; Sladky 2004; Hicks et al 2010). Manifestations can include orthostatic hypotension, pupillary dysfunction, sweating abnormalities, and sinus tachycardia (England 1990). In addition, respiratory failure due to involvement of the muscles of respiration results in ventilator dependence in 16% to 28% of children (Korinthenberg and Monting 1996; Delanoe et al 1998). Laboratory evaluation reveals an elevated CSF protein out of proportion to CSF pleocytosis, although this may not be seen within the first 48 hours of symptom onset. In addition, the syndrome of inappropriate antidiuretic syndrome (SIADH) can also be associated with Guillain-Barré syndrome in adults (Saifudheen et al 2011), especially those requiring ventilator support, and should be monitored for and treated in patients of all ages. After several days, abnormalities in conduction velocities, F waves, and compound motor action potential can be seen in electrophysiologic studies. The lumbosacral MRI can demonstrate enhancement of the nerve roots. Although the term Guillain-Barré syndrome traditionally refers to the syndrome of acute inflammatory demyelinating polyneuropathy (AIDP), other variants exist to include: acute motor and sensory axonal neuropathy (AMSAN), acute motor axonal neuropathy (AMAN), Miller Fisher syndrome, and polyneuritis cranialis. Miller Fisher syndrome is a variant seen in children and is characterized by the triad of ophthalmoplegia, ataxia, and areflexia with relatively little weakness and is associated with serum anti-gq1b antibodies (Marks et al 1977; Ropper 1992). MRI neuroimaging of the brain in patients with Miller Fisher syndrome may also reveal nerve enhancement, specifically of the cranial nerves (Hsieh et al 2008). Prognosis and complications In general, most children (over 90%) with Guillain-Barré syndrome show a full recovery of motor function (Korinthenberg and Monting 1996; Kalra et al 2009). In a series, the median time from onset of symptoms to first recovery was 17 days, to walk unaided, 37 days, and to be symptom-free, 66 days (Korinthenberg and Monting 1996). Patients with the axonal form of Guillain-Barré syndrome have a poorer prognosis in adult series, with a median time to walk with assistance about 32 days (Ho et al 1997). The full recovery period is longer than the period of time the child was sick, often requiring weeks to months, with a median estimated time to maximum recovery of 7 months (Bradshaw and Jones 1992). Although the majority of patients achieve their maximum amount of functional improvement within the first 6 months, some recovery does continue to occur even after the first year (Kalra et al 2009). However, some children will have persistent symptoms of paresthesias, unsteadiness of gait in the dark, painful hands or feet, or fatigue (Roodbol et al 2014). The most serious complications occur with weakness of the respiratory muscles. Many seriously affected individuals will need respiratory support, from 16% to 28% (Korinthenberg and Monting 1996; Delanoe et al 1998; Kalra et al 2009). During the progression of the disease, attention should be paid to the child's respiratory status, and measurements such as vital capacity can provide objective data to follow. Although the overall outcome for childhood Guillain-Barré syndrome is favorable, the need for ventilation is a risk factor associated with those with a poor

3 functional outcome (Kalra et al 2009). In addition, residual fatigue can be reported after Guillain-Barre syndrome and may be related to more pronounced axonal loss (Drenthen et al 2013). Recurrences are uncommon but can occur in children. Some may have a chronic progressive course, whereas others may show recurrences or relapses. When this occurs, the possibility of chronic inflammatory demyelinating polyneuropathy (CIDP), should also be considered. Clinical vignette A 5-year-old girl presented with inability to walk for 2 days. She had an illness characterized by fever and runny nose but seemed to recover fully from these symptoms. On exam, she had weakness in her legs and arms. Sensory exam appeared normal. Reflexes were not elicitable. A lumbar puncture showed 5 white blood cells, 0 red blood cells, a protein of 160 mg/dl, and a normal glucose. After Guillain-Barré syndrome was suspected, the child was started on intravenous immunoglobulin. During the first 2 days of treatment, she showed progressive weakness. Daily pulmonary function testing showed progressive worsening. A nerve conduction velocity test at that time showed prolonged distal latencies and abnormal F waves. On the third treatment day, she stabilized, and by the fifth treatment day she had slightly improved from her nadir. One month later, follow-up showed continued improvement, but she was still weak and reflexes remained difficult to obtain. By 6 months, she was back to normal. Biological basis Etiology and pathogenesis Guillain-Barré syndrome is believed to be an autoimmune mediated process. A preliminary study indicates macrophage migration inhibitory factor may play a role (Nicoletti et al 2005). Several infections (Epstein-Barr virus, cytomegalovirus, mycoplasma, campylobacter), as well as immunizations, have been known to precede the illness (Stratton et al 1994). The role of mycoplasma pneumonia has been reported, occurring more frequently in children than adults, and it has been associated with IgG antibodies against galactocerebroside, a major glycolipid found in both the peripheral and central nervous system (Meyer Sauteur et al 2016). The immune-mediated targets in Guillain- Barré syndrome can include the myelin sheaths of the peripheral nerves or the axons themselves. Of note, although the incidence of Guillain-Barré after Meningococcal conjugate vaccine is currently under close surveillance, an increased risk has not been clearly defined (CDC 2006; De Wals et al 2008). Occasionally, surgery is noted to be a precipitating factor. In the demyelinating form of Guillain-Barré syndrome, demyelination and mononuclear infiltration are seen. Lymphocytes and macrophages surround endoneural vessels and cause an adjacent demyelination. These lesions can be discrete and are scattered through the peripheral nervous system although there may be a predilection for inflammation of the nerve roots (Ropper 1992). The conduction block and demyelination of the motor nerves results in the progressive weakness of this syndrome. Similarly, the involvement of the sensory nerves leads to pain and paresthesias. Many authors believe that the mechanism of disease involves an abnormal T-cell response, precipitated by a preceding infection (Ropper 1992). A variety of specific antigens may be involved in this response, including myelin P- 2, GM1, and GQ1 gangliosides (Rostami 1993). GD1b is a ganglioside associated with primary sensory neurons, and anti-gd1b antibodies are seen in a small percentage of patients (Miyazaki et al 2001). Although rare, other antiganglioside antibodies have been found in children with Guillain-Barré syndrome; the antibodies are seen most often in patients with a preceding Campylobacter jejuni infection (Schessl et al 2007). There does appear to be a regional geographic difference in the incidence of Guillain-Barré subtypes. The classic demyelinating subtype, AIDP, is the predominant subtype in most western countries to include the United States and Europe. In contrast, the axonal subtype of AMAN is the predominant subtype in Asia, to include China and Japan, and also in Mexico (Nachamkin et al 2007). In Mexican children, AMAN was often associated with Campylobacter infection, and many of these patients also had detectable serum antiglycolipid antibodies. In Northern China, epidemics of the

4 AMAN variant of Guillain-Barré syndrome, particularly during the summer months, have also been associated with Campylobacter jejuni infection, with many of these patients also having detectable antiglycolipid antibodies (Griffin et al 1995; Ho et al 1995). In this axonal form of Guillain-Barré syndrome, biopsy specimens reveal Wallerian-like degeneration of fibers in the ventral and dorsal nerve roots, with only minimal demyelination or lymphocytic infiltration (Griffin et al 1996). These axonal lesions affect both sensory and motor fibers. Although this form of Guillain-Barré syndrome has been associated with Campylobacter infection, it appears to be a rare complication of such infection (McCarthy et al 1999). Guillain-Barré syndrome is associated with the HS:19 serotype of Campylobacter jejuni, but it can be seen in other serotypes as well (Engberg et al 2001). Epidemiology" The age-specific incidence of Guillain-Barré syndrome is 1.5/100,000 in persons younger than 15 years of age (Prevots and Sutter 1997). Approximately one third of cases in children occur before the age of 3 years, with a mean age of 6 years, when defining children as younger than 15 years of age (Delanoe et al 1998). Prevention No specific methods of prevention are known. Over time, some vaccines have been modified to include less neural antigens in the hopes of reducing the incidence of Guillain-Barré syndrome. Differential diagnosis The differential diagnosis of Guillain-Barré syndrome in childhood is primarily that of a progressive, symmetric weakness. Myelopathy (eg, cord compression syndromes, transverse myelitis) can sometimes present with progressive weakness and is the most important etiology to rule out in a patient with acute or subacute weakness. The physical exam (or spinal MRI) should help differentiate a spinal cord syndrome from a diffuse neuropathy. Although the finding of upper motor neuron signs can point the examiner more toward a central process such as a myelopathy, it is especially important to note that a myelopathy can present initially with a flaccid paralysis with absent deep tendon reflexes in the acute stage of injury, thus, resembling the examination of the patient with Guillain-Barré syndrome. In infants particularly, botulism should be a consideration. In botulism there is early involvement of the extraocular muscles as well as constipation. Additionally, when ophthalmoplegia is present, myasthenia gravis is a consideration. Fatigueability on examination and nerve conduction velocity and EMG findings can help distinguish between these conditions. A presentation similar to Guillain-Barré syndrome can occur in certain infections such as poliomyelitis, Lyme disease, and HIV. In these latter cases, the lumbar puncture will typically show a CSF pleocytosis. Other acute neuropathies from lead, heavy metals, or vincristine also cause a predominantly motor neuropathy. Tick paralysis can also cause an ascending paralysis; all children with suspected Guillain Barré syndrome should have a complete examination of the skin for ticks. Often improvement is dramatic after the tick removal, especially in North America, as opposed to Australian cases. Occasional reports of organophosphate poisoning present with a Guillain-Barré syndromelike picture. Finally, when dealing with a population that is not completely immunized, diphtheria should also be in the differential diagnosis, especially in children with a recent history of pharyngitis. Diagnostic workup The diagnosis is made by the presence of a progressive ascending weakness with areflexia. A lumbar puncture, electrodiagnostic studies, or, occasionally, MRI findings can give support for this diagnosis. The lumbar puncture will be suggestive of a demyelination (increased protein) without evidence of active infection (lack of CSF pleocytosis). Guillain and Barré originally noted this. The spinal fluid findings may be normal within the first 48 hours of symptoms, and occasionally, the protein may not rise for a week (England 1990). Most patients will have less than 10 leukocytes per cubic mm, but occasionally, a mild elevation of between 10 and 50 cells is seen (England 1990; Delanoe et al 1998). Electrodiagnostic studies within the first week of the onset of symptoms reveal a prolonged or absent F response (88%), prolonged distal latencies (75%), conduction block (58%), and reduced conduction velocity (50%). By the second week of the illness, reduced compound muscle action potential (100%), prolonged distal latencies (92%), and reduced motor conduction velocities (84%) are seen (Delanoe et al 1998). The results on nerve conduction studies closely correlate with pathological changes seen by nerve biopsy (Lu et al 2000).

5 Spinal MRI looking at lumbosacral root enhancement appears to be a sensitive diagnostic test in children with Guillain- Barré and should be considered when there is clinical uncertainty, or at the preference of the clinician. In a study looking at MRI findings at a mean of 13 days after start of symptoms, enhancement of the cauda equina nerve roots with gadolinium on lumbosacral MRI was 83% sensitive of acute Guillain-Barré syndrome, and present in 95% of "typical" cases (Gorson et al 1996). Nerve root enhancement can be seen as early as 2 days after symptom onset, and a study reported that 100% of patients eventually had spinal nerve root enhancement on repeat imaging (Mulkey et al 2010). Anterior nerve root enhancement is usually the predominant pattern (Yikilmaz et al 2010). Management Multiple studies have used intravenous immunoglobulin to treat the symptoms of Guillain-Barré syndrome. Intravenous immunoglobulin seems most helpful in reducing the severity of the disease, as well as the duration of symptoms. Long-term outcome, however, may not be affected. Studies have demonstrated that an effect of the IVIG is to neutralize neuromuscular blocking antibodies (Buchwald et al 2002). Several IVIG regimens have been utilized. One regimen includes daily intravenous immunoglobulin for 5 days at a dose of 0.4 gm/kg per day (van der Meche and Schmitz 1992; Abd-Allah et al 1997; Korinthenberg 2005), which results in an improvement within a mean of 2 to 3 days after the start of therapy (Abd-Allah et al 1997). Other authors use 2 gm/kg of intravenous immunoglobulin given as a single dose or 1 gm/kg for 2 days (Zafeiriou et al 1997; Korinthenberg 2005). One study compared the outcome of 0.4 gm/kg per day given for 3 days versus 6 days (Raphael et al 2001a). In that study, the 6 days of IVIG was superior when time to walking was used as an endpoint. When comparing treatments of 1 gm/kg for 2 days versus 0.4 gm/kg over 5 days, no significant difference in the effectiveness was noted in the 2 treatment regimens. However, early relapses were more frequently observed in the shorter treatment group (Korinthenberg 2005). Plasmapheresis is also an option. Studies in children using both historical and case controls indicate that plasmapheresis may decrease the severity and shorten the duration of Guillain-Barré syndrome (Epstein and Sladky 1990; Lamont et al 1991; French Cooperative Group on Plasma Exchange in Guillain-Barré; Syndrome 1997). Plasma exchange was most beneficial when started within 7 days of the onset of symptoms but is still beneficial in patients treated up to 30 days after disease onset (Raphael et al 2001b). For most studies, the results of plasmapheresis and intravenous immunoglobulin seem similar, with possibly fewer side effects seen with intravenous immunoglobulin (van der Meche and Schmitz 1992; Bril et al 1996). However, in a prospective randomized study in children comparing plasma exchange and intravenous immunoglobulin, the group treated with plasma exchange had a shorter duration of mechanical ventilation (El-Bayoumi et al 2011). However, no significant differences in PICU stay or short term neurologic outcome were noted (El-Bayoumi et al 2011). Although steroids have been previously used to treat Guillain- Barré syndrome, current data suggest that these agent provide no benefit (Hughes 1991). If IVIG and plasmapheresis are unavailable, exchange transfusion as a low-cost alternative has been suggested but is not an accepted first-line therapy (Baranwal et al 2006). A practice parameter by the American Academy of Neurology states that both IVIG and plasmapheresis are treatment options for children with severe Guillain-Barré syndrome although there are no adequate randomized controlled trials specifically in children (Hughes et al 2003). Both IVIG and plasmapheresis are efficacious, and combining the treatments provides no significant benefit (Hughes et al 2004). Patients' vital signs and respiratory capacity should be monitored. When vital capacity falls below 15 ml/kg of body weight, arterial PO2 falls below 70 mm/hg, or there is significant fatigue, intubation and mechanical ventilation should be considered (Ropper and Kehne 1985). Orthostatic hypotension and urinary retention may also cause patients significant problems during the acute phase of the illness. Attention should also be paid to possible decubitus ulcers and contractures in patients who are severely ill or who have a particularly prolonged course. In addition, chronic pain should be addressed using standard medications for neuropathic pain, although corticosteroid therapy has also been reported to decrease pain in pediatric Guillain-Barre syndrome (Kajimoto et al 2015). Long-term physical therapy may provide a benefit to patients during the recovery phase of the illness. Acknowledgement

6 The views expressed are those of the author and do not reflect the official policy or position of the United States Air Force, United States Army, Department of Defense, or the United States Government. References cited Abd-Allah SA, Jansen PW, Ashwal S, Perkin RM. Intravenous immunoglobulin as therapy for pediatric Guillain-Barré syndrome. J Child Neurol 1997;12: PMID Baranwal AK, Ravi RN, Singh R. Exchange transfusion: a low-cost alternative for severe childhood Guillain-Barre syndrome. J Child Neurol 2006;21: PMID Bradshaw DY, Jones HR Jr. Guillain-Barré syndrome in children: clinical course, electrodiagnosis, and prognosis. Muscle Nerve 1992;15: PMID Bril V, Ilse WK, Pearce R, Dhanani A, Sutton D, Kong K. Pilot trial of immunoglobulin versus plasma exchange in patients with Guillain-Barré syndrome. Neurology 1996;46: PMID Buchwald B, Ahangari R, Weishaupt A, Toyka KV. Intravenous immunoglobulins neutralize blocking antibodies in Guillain-Barré syndrome. Ann Neurol 2002;51: PMID CDC. Update: Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine United States, June 2005-September MMWR Morb Mortal Wkly Rep 2006;55: PMID Delanoe C, Sebire G, Landrieu P, Huault G, Metral S. Acute inflammatory demyelinating polyradiculopathy in children: clinical and electrodiagnostic studies. Ann Neurol 1998;44: PMID De Wals P, Deceuninck G, Boucher RM, Ouakki M. Risk of Guillain-Barre syndrome following serogroup C meningococcal conjugate vaccine in Quebec, Canada. Clin Infect Dis 2008;46:e75-7. PMID Drenthen J, Jacobs BC, Maathius EM, van Doorn PA, Visser GH, Blok JH. Residual fatigue in Guillain-Barre syndrome is related to axonal loss. Neurology 2013;81(21): PMID El-Bayoumi MA, El-Refaey AM, Abdelkader AM, et al. Comparison of intravenous immunoglobulin and plasma exchange in treatment of mechanically ventilated children with Guillain Barre syndrome: a randomized study. Crit Care 2011;15:R PMID Engberg J, Nachamkin I, Fussing V, et al. Absence of clonality of Campylobacter jejuni in serotypes other than HS:19 associated with Guillain-Barré syndrome and gastroenteritis. J Infect Dis 2001;184: PMID England JD. Guillain-Barré syndrome. Ann Rev Med 1990;41:1-6. PMID Epstein MA, Sladky JT. The role of plasmapheresis in childhood Guillain-Barré syndrome. Ann Neurol 1990;28:65-9. PMID French Cooperative Group on Plasma Exchange in Guillain-Barré Syndrome. Appropriate number of plasma exchanges in Guillain-Barré syndrome. Ann of Neurology 1997;41: PMID Gorson KC, Ropper AH, Muriello MA, Blair R. Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barré syndrome. Neurology 1996;47: PMID Griffin JW, Li CY, Ho TW, et al. Guillain-Barré syndrome in northern China. The spectrum of neuropathological changes in clinically defined cases. Brain 1995;118: PMID Griffin JW, Li CY, Ho TW, et al. Pathology of the motor-sensory axonal Guillain-Barré syndrome. Ann Neurol 1996;39: PMID Hicks CW, Kay B, Worley SE, Moodley M. A clinical picture of Guillain-Barre syndrome in children in the United States. J Child Neurol 2010;25(12): PMID Ho TW, Li CY, Cornblath DR, Asbury AK, Griffin JW, McKhann GM. Patterns of recovery in the Guillain-Barré syndromes.

7 Neurology 1997;48: PMID Ho TW, Mishu B, Li CY, et al. Guillain-Barré syndrome in northern China. Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies. Brain 1995;118: PMID Hsieh DT, Singh R, Zecavati N, Emmanuel B. Teaching Video NeuroImage: Near complete ophthalmoplegia in GQ1b antibody-positive Miller Fisher: video and MRI correlation. Neurology 2008;71:e31. PMID Hughes RA. Ineffectiveness of high-dose intravenous methylprednisolone in Guillain-Barré syndrome. Lancet 1991;338(8775):1142. PMID Hughes RA, Raphael JC, Swan AV, Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev 2004;(1):CD PMID Hughes RA, Wijdicks EF, Barohn R, et al. Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003:61(6): PMID Jones HR. Guillain-Barré syndrome: perspectives with infants and children. Seminars in Pediatric Neurology 2000;7: PMID Kajimoto M, Koga M, Narumi H, Inoue H, Matsushige T, Ohga S. Successful control of radicular pain in a pediatric patient with Guillain-Barre syndrome. Brain Dev 2015;37(9): PMID Kalra V, Sankhyan N, Sharma S, Gulati S, Choudhry R, Dhawan B. Outcome in childhood Guillain-Barre syndrome. Indian J Pediatr 2009;76: PMID Korinthenberg R, Monting JS. Natural history and treatment effects in Guillain-Barré syndrome: a multicentre study. Arch Dis Child 1996;74: PMID Korinthenberg R, Schessl J, Kirschner J, Monting JS. Intravenously administered immunoglobulin in the treatment of childhood Guillain-Barré syndrome: a randomized trial. Pediatrics 2005;116(1):8-14. PMID Lamont PJ, Johnston HM, Berdoukas VA. Plasmapheresis in children with Guillain-Barré syndrome. Neurology 1991:41: PMID Lu JL, Sheikh KA, Wu HS, Zhang J, et al. Physiologic-pathologic correlation in Guillain-Barré syndrome in children. Neurology 2000;54:33-9. PMID Marks HG, Augustyn P, Allen RJ. Fisher's syndrome in children. Pediatrics 1977;60: PMID Matsushita M, Kitoh H, Itomi K, et al. Orthopedic manifestations and diagnostic clues in children with Guillain-Barre syndrome. J Child Orthop 2013;7(3): PMID McCarthy N, Andersson Y, Jormanainen V, Gustavsson O, Giesecke J. The risk of Guillain-Barré syndrome following infection with Campylobacter jejuni. Epidemiol Infect 1999;122:15-7. PMID Meyer Sauteur PM, Huizinga R, Tio-Gillen AP, et al. Mycoplasma pneumoniae triggering the Guillain-Barre syndrome: a case-controlled study. Ann Neurol 2016;80(4): PMID Miyazaki T, Kusunoki S, Kaida K, Shiina M, Kanazawa I. Guillain-Barré syndrome associated with IgG monospecific to ganglioside GD1b. Neurology 2001;56: PMID Mulkey SB, Glasier CM, El-Nabbout B, et al. Nerve root enhancement on spinal MRI in pediatric Guillain-Barre syndrome. Pediatr Neurol 2010;43(4): PMID Nachamkin I, Barbosa PA, Ung H, et al. Patterns of Guillain-Barré syndrome in children: results from a Mexican population. Neurology 2007;69: PMID Nicoletti F, Creange A, Orlikowski D, et al. Macrophage migration inhibitory factor (MIF) seems crucially involved in

8 Guillain-Barré syndrome and experimental allergic neuritis. J Neuroimmunol 2005;168(1-2): PMID Prevots DR, Sutter RW. Assessment of Guillain-Barré syndrome mortality and morbidity in the United States: implications for acute flaccid paralysis surveillance. J Infect Dis 1997;175:S PMID Raphael JC, Chevret S, Harboun M, Jars-Guincestre MC, The French Guillain-Barré Syndrome Cooperative Group. Intravenous immune globulins in patients with Guillain-Barré syndrome and contraindications to plasma exchange: 3 days versus 6 days. J Neurol Neurosurg Psychiatry 2001a;71: PMID Raphael JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev 2001b;2:CD PMID Roodbol J, de Wit MC, Aarsen FK, Catsman-Berrevoets CE, Jacobs BC. Long-term outcome of Guillain-Barre syndrome in children. J Peripher Nerv Syst 2014;19: PMID Roodbol J, De Wit MC, Walgaard C, et al. Recognizing Guillain-Barre syndrome in preschool children. Neurology 2011;76: PMID Ropper AH. The Guillain-Barré syndrome. N Engl J Med 1992;326: PMID Ropper AH, Kehne SM. Guillain-Barré syndrome: management of respiratory failure. Neurology 1985;35: PMID Rostami AM. Pathogenesis of immune-mediated neuropathies. Pediatr Res 1993;3:S90-4. PMID Saifudheen K, Jose J, Gafoor VA, Musthafa M. Guillain-Barre syndrome and SIADH. Neurology 2011;76: PMID Schessl J, Koga M, Funakoshi K, et al. Prospective study on anti-ganglioside antibodies in childhood Guillain-Barre syndrome. Arch Dis Child 2007;92: PMID Sladky JT. Guillain-Barre syndrome in children. J Child Neurol 2004;19: PMID Stratton KR, Howe CJ, Johnston RB Jr. Adverse events associated with childhood vaccines other than pertussis and rubella. Summary of a report from the Institute of Medicine. JAMA 1994;271: PMID Tosun A, Dursun S, Akyildiz UO, Oktay S, Tataroglu C. Acute motor-sensory axonal neuropathy with hyperreflexia in Guillain-Barre syndrome. J Child Neurol 2015;30(5): PMID van der Meche FG, Schmitz PI. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. Dutch Guillain Barré Study Group. N Engl J Med 1992;326: PMID Yikilmaz A, Doganay S, Gumus H, Per H, Kumandas S, Coskun A. Magnetic resonance imaging of childhood Guillain- Barre syndrome. Childs Nerv Syst 2010;26(8): PMID Zafeiriou DI, Kontopoulos EE, Katzos GS, Gombakis NP, Kanakoudi FG. Single dose immunoglobulin therapy for childhood Guillain-Barré syndrome. Brain Dev 1997;19: PMID **References especially recommended by the author or editor for general reading. Former authors Teng Ji MD, Kenneth J Mack MD PhD (original authors), and Christina D Casas MD ICD and OMIM codes ICD codes ICD-9: Guillain-Barré syndrome: 357.0

9 ICD-10: Guillain-Barré syndrome: G61.0 OMIM numbers Guillain-Barré syndrome, familial: # Profile Age range of presentation 0-01 month months years years years years years 65+ years Sex preponderance male>female, >2:1 male>female, >1:1 Family history none Heredity none Population groups selectively affected none selectively affected Occupation groups selectively affected none selectively affected Differential diagnosis list botulism myasthenia gravis myelopathies Lyme disease HIV neuropathies from lead, heavy metal, and vincristine tic paralysis organophosphate poisoning diphtheria polyneuropathy Associated disorders Acute inflammatory demyelinating polyneuropathy Acute inflammatory demyelinating polyradiculopathy Chronic inflammatory demyelinating polyneuropathy Fisher syndrome

10 Other topics to consider Chronic inflammatory demyelinating polyradiculoneuropathy Epstein-Barr virus infections of the nervous system Sensory neuropathies associated with anti-gd1b ganglioside antibodies Copyright MedLink Corporation. All rights reserved.