Guillain Barré syndrome

J B Winer

AbstractGuillain Barré syndrome is one of the bestexamples of a post infectious immune dis-ease and oVers insights into the mech-anism of tissue damage in other morecommon autoimmune diseases. Control-led epidemiological studies have linked itto infection with Campylobacter jejuni inaddition to other viruses including cy-tomegalovirus and Epstein Barr virus.The syndrome includes several pathologi-cal subtypes, of which the most common isa multifocal demyelinating disorder of theperipheral nerves in close association withmacrophages. Evidence from histologicalexamination of peripheral nerve biopsyand postmortem samples suggests thatboth cell mediated and humoral mecha-nisms are involved in the pathogenesis.Immunological studies suggest that atleast one third of patients have antibodiesagainst nerve gangliosides, which in somecases also react with constituents of theliposaccharide of C jejuni. In the MillerFisher variant of the disease, these anti-ganglioside antibodies have been shown toproduce neuromuscular block, and may inpart explain the clinical signs of thatdisorder. Treatment with both intra-venous immunoglobulin and plasma ex-change reduces the time taken forrecovery to occur, although mortalityremains around 8%, with about 20% ofpatients remaining disabled.(J Clin Pathol: Mol Pathol 2001;54:381–385)

Keywords: Guillain Barré syndrome; Campylobacterjejuni; antiganglioside antibodies; intravenous immu-noglobulin treatment; plasma exchange

Guillain Barré syndrome remains one of themost fascinating yet challenging conditionsdespite considerable advances in its under-standing and treatment over the past 10 years.

Described originally by French physiciansworking in the Sixth Army camp during theFirst World War,1 it has remained relativelyrare, but so striking in its presentation that fewdoctors will not remember the clinical features.Current epidemiological studies suggest anincidence of between 1 and 2/100 000 withslightly, more male individuals aVected thanfemales.2 The incidence rises with age, al-though there is a minor peak among youngadults.3 Its relation to infection and its place asan autoimmune disease have stimulated muchresearch over the years, which has beenrewarded by the discovery of antigangliosideantibodies in at least one third of patients.4

These antibodies appear to crossreact withantigens in the lipopolysaccharide of someantecedent infective agents, providing a possi-ble mechanism for the disease.5 Although the

clinical syndrome presents with a rapidlyprogressive neuropathy, it is now recognisedthat several pathologically and probably aetio-logically distinct subtypes exist (table 1).

It should also be remembered that GuillainBarré syndrome is but one of a spectrum ofdiseases, identified by its rapid presentation,but closely allied to more chronic diseases,such as subacute inflammatory demyelinatingpolyneuropathy and chronic inflammatorydemyelinating neuropathy (table 2). The diag-nostic criteria and treatment of these disordersdiVer, although there are many pathologicalsimilarities.

Clinical featuresCriteria for the diagnosis of Guillain Barrésyndrome were initially devised to investigatethe possible association of this disease withswine flu vaccination in the 1970s.6 These cri-teria have been redefined in the light ofadvances in the electrophysiology of GuillainBarré syndrome.7 Required criteria for thediagnosis include progressive weakness of morethan two limbs, areflexia, and progression forno more than four weeks. Other causes of anacute neuropathy such as lead poisoning,vasculitis, botulism, and porphyria requireexclusion. Supportive criteria include relativelymild sensory signs, raised protein in thecerebrospinal fluid (CSF), with a relativelynormal cell count, and neurophysiological evi-dence of conduction block. Weakness isfrequently proximal and distal, unlike dyingback axonopathies, and respiratory involve-ment occurs in about a quarter of cases. TheCSF protein may be normal in the first week ofthe illness8 but may then rise to several g/dl.The CSF cell count usually remains below 500cells/litre. Oligoclonal bands are sometimesfound in the CSF. Routine blood testssometimes reveal a raised sedimentation ratewith hyponatraemia from inappropriate anti-diuretic hormone release, and mild impairmentof liver function tests is not uncommon.

Antecedent eventsAlthough Guillain, Barré, and Strohl did notcomment on the association of this illness withinfection, extensive clinical observationssupported by epidemiological studies suggest

Table 1 Subtypes of Guillain Barré syndrome

Acute inflammatory demyelinating polyneuropathyAcute motor axonal neuropathyAcute motor and sensory axonal neuropathyMiller Fisher syndrome

Table 2 Spectrum of demyelinating neuropathies

Guillain Barré syndromeSubacute demyelinating polyneuropathyChronic inflammatory demyelinating polyneuropathy

J Clin Pathol: Mol Pathol 2001;54:381–385 381

Department ofNeurology, QueenElizabeth Hospital,Edgbaston,Birmingham B15 2TH,UKJ B Winer

Correspondence to:Dr Winerj.b.winer@bham.ac.uk

Accepted for publication8 March 2001

www.molpath.com

on 1 Septem

ber 2018 by guest. Protected by copyright.

http://mp.bm

j.com/

Mol P

ath: first published as 10.1136/mp.54.6.381 on 1 D

ecember 2001. D

ownloaded from

that about 75% of patients have a history of pre-ceding symptoms of infection.9 Serologicalstudies reveal evidence of antecedent infectionin about 30%9–11 to 50% of cases.12 These dataare supported by accounts of outbreaks of Guil-lain Barré syndrome and an association betweenclinical cases of food poisoning and GuillainBarré syndrome within communities. Case con-trolled studies confirm a significant associationwith C jejuni,13 cytomegalovirus,14 and probablyEpstein-Barr virus.14 Of these, the associationwith C jejuni remains the most highly studied.Numerous anecdotal reports of associationswith other infections exist in the literature. Someimmunisations also appear to be recognisedtriggers of the disease, including swine flu15 andrabies.16 Serological evidence of C jejuni infec-tion occurs in about 30% of patients with Guil-lain Barré syndrome and appears to be associ-ated with slightly more severe disease and withacute motor axonal neuropathy (AMAN) vari-ants.13 17 Many examples of persistent excretionof this organism in the stools of clinical cases ofGuillain Barré syndrome are described,strengthening the association.18

PathologyThe studies of Asbury and colleagues19 sug-gested that the earliest hall mark of GuillainBarré syndrome was the presence of perifas-cicular lymphocytic cuVs of small vessels in theendoneurium and perineurium. This appearsto be associated with demyelination, which istypically macrophage associated.20 In thisregard, the pathology has many similaritieswith the animal model, experimental allergicneuritis (EAN).21 More recent pathologicalstudies have shown that several pathologicalsubtypes of Guillain Barré syndrome exist,although the demyelinating form of the diseaseis the most common, and probably representsat least 75% of cases.22 Some cases of GuillainBarré syndrome are associated with a primarilyaxonal process, in which macrophages may befound in close proximity to the axon, withsparing of myelin.23 This histological findinghas been interpreted as indicating an immuno-logical attack on antigens of axonal origin,rather than a myelin antigen in demyelinatingforms of the disease.

Still other cases of the disease appear toinvolve both sensory and motor axons and suchcases are termed acute motor and sensoryaxonal neuropathy (AMSAN). This variant ofthe disease appears to be the most uncommonand perhaps accounts for only 5% of the clini-cal syndrome.

ElectrophysiologyEarly neurophysiological studies revealed that,despite the demyelinating pathology, manypatients retained normal conduction velocitiesuntil the disease was well established. The ear-liest changes appear to be a delay in F waves(implying root demyelination)24 and reductionin nerve motor action potentials. This lastabnormality may be diYcult to determine pre-cisely for technical reasons until the abnormal-ity is severe. Patients with early Guillain Barrésyndrome frequently have conduction block or

dispersion of the responses at sights of naturalnerve compression, such as carpal tunnel. Theextent of reduction in the motor nerve actionpotentials appears to correlate with prognosis.It is exceptional for extensive neurophysiologi-cal tests to be normal in Guillain Barrésyndrome, but this does sometimes occur,presumably because demyelinating lesionshave occurred in anatomical sites that areexclusively proximal and not amenable to easyneurophysiological study.

ImmunologyThe earliest immunological studies of GuillainBarré syndrome were limited to crude comple-ment fixation tests to nerve antigens. Suchstudies suggested minor abnormalities in only asmall proportion of cases.25 Nevertheless, thedramatic response of demyelinating cases ofGuillain Barré syndrome to treatment withplasma exchange strengthened the view that aplasma derived factor must have a role in theaetiology of the syndrome. In the mid-1980sKoski et al described a C1 esterase techniquethat appeared to detect subtle complementfixation in most patients with Guillain Barrésyndrome26 and, furthermore, the concentra-tions fell during the convalescent stage of thedisease. Unfortunately, this test proved diYcultto reproduce and few other laboratories coulddemonstrate such striking abnormalities. Thediscovery of antiganglioside antibodies in theserum of patients with Guillain Barré syn-drome has sparked of an enormous prolifera-tion of publications. The frequency of suchantibodies varies from as low as 29%27 up tonearly 70%,28 although the average figure isprobably around 30%. Patients with MillerFisher syndrome have detectable anti-GQ1bantibodies at a much higher frequency, prob-ably around 95%.29 30 Gangliosides are widelydistributed in the nervous system and may havea variety of functional roles. The structure ofgangliosides (fig 1) involves several repeatingsubunits, which can be antigenic. Thus,antiganglioside antibodies have diVerent spe-cificities and these may overlap. Antibodies thatrecognise the NeuACNeuAC epitope willcrossreact with several diVerent gangliosides,making the importance of antiganglioside anti-bodies more diYcult to interpret. The patternof reactivity of a particular patient’s serum withseveral diVerent gangliosides helps to definethe exact specificity of the antibody. This canbe seen most clearly when monoclonal anti-bodies against gangliosides are produced.32

The presence of antiganglioside antibody in aproportion of patients with Guillain Barré syn-drome does not imply that the antibodies arepathogenetic. However, there appears to be agrowing body of evidence in favour of thehypothesis that the fine specificity of theantiganglioside antibodies in at least a pro-portion of patients with Guillain Barré syn-drome determines the pattern of clinical andpathological involvement. In support of thishypothesis is the observation that patients withaxonal forms of Guillain Barré syndrome aremore likely to have antiganglioside antibodiesthat recognise the ganglioside GD1a.23

382 Winer

www.molpath.com

on 1 Septem

ber 2018 by guest. Protected by copyright.

http://mp.bm

j.com/

Mol P

ath: first published as 10.1136/mp.54.6.381 on 1 D

ecember 2001. D

ownloaded from

In Miller Fisher syndrome, the clinical symp-toms relate to dysfunction of the third, fourth,and sixth cranial nerves, similar to ocularmyasthenia. Biochemical studies suggest thatthese cranial nerves contain a considerableamount of GQ1b,33 and Miller Fisher serum aswell as monoclonal antibodies will immunos-tain these nerves in section.34 Serum frompatients with Miller Fisher syndrome contains ablocking factor, which will initially depolarisethe neuromuscular junction in a mouse hemidi-aphragm preparation and then completelyblock it in a mechanism that resembles that ofthe toxin Lathratoxin.34 The responsible factor

in the serum appears to be in the IgG fraction.Furthermore, monoclonal anti-GQ1b antibodywill immunostain the neuromuscular junctionof the mouse, and the pattern of staining exactlymimics that found with fluorescent labelledbungarotoxin, which is known to combine withthe á subunit of the acetyl choline receptor.34

This evidence strongly suggests that at least inMiller Fisher syndrome the ophthalmoparesisresults from a direct action of anti-GQ1bantibodies on the neuromuscular junctionbetween the cranial nerves and ocular muscles.

Complete proof of this hypothesis requiresproduction of ocular dysfunction by passive

Figure 1 The NeuAc motif is shared between gangliosides GD1b, GT1b, and GQ1b (shaded, not hatched). Other similarities include the Gal (â1-3)GAL/NAc epitope shared between GM1 and GD1b. SGPG, sulphate-3-glucuronyl paragloboside; Glc, glucose; Gal, galactose; GalNAc, N-acetylgalactosamine;GlcNAc, N-actylglucosamine; GlcUA, glucuronic acid; NeuAc, N-acetylneuramic acid (sialic acid). From Dalakas and Quarles.31

SGPG

Gal

GlcNAc

Gal

Glc

SO3GlcUA

GM1

Gal

NeuAc

GalNAc

Gal

Glc

GD1a

Gal

NeuAc

NeuAc

Gal

GalNAc

Glc

GD1b

Gal

GalNAc

Gal

Glc

NeuAc

NeuAc

GT1b

Gal

NeuAc

NeuAc

NeuAc

GalNAc

Gal

Glc

GQ1b

Gal

NeuAc

NeuAc

NeuAc

NeuAc

Gal

GalNAc

Glc

Guillain Barré syndrome 383

www.molpath.com

on 1 Septem

ber 2018 by guest. Protected by copyright.

http://mp.bm

j.com/

Mol P

ath: first published as 10.1136/mp.54.6.381 on 1 D

ecember 2001. D

ownloaded from

transfer of antibody, and this has not yet beenachieved, largely because of the lack of anappropriate animal model. In Guillain Barrésyndrome, the lack of antiganglioside antibod-ies in a large proportion of patients arguesagainst this mechanism in all cases, but it couldexplain a proportion of cases.

Another possible antibody that might be rel-evant is some of these patients is antibodydirected towards the myelin protein PMP 22.Genetic abnormalities of PMP 22 expressionunderlie the demyelinating form of CharcotMarie tooth disease and point mutations ofPMP 22 can produce the same phenotype. Theserum of patients with Guillain Barré syn-drome contains antibodies against PMP 22,35

and the protein can induce EAN in Lewis ratsin an experimental model. It is possible thatGuillain Barré syndrome may turn out to bethe result of a variety of diVerent antibodies, ofwhich antiganglioside antibodies are simply themost common.

The classic histological studies of GuillainBarré syndrome noted the presence of infil-trates of lymphocytes around small vessels,19

and the similarities of this finding with EANsuggested a role for T cells in the pathogenesisof Guillain Barré syndrome. Initial studies of Tcells in Guillain Barré syndrome were conflict-ing, but only a very small proportion of caseshad evidence of T cell proliferation to putativeprotein antigens.36 The peripheral blood ofpatients with inflammatory neuropathy con-tains activated T cells37 and peripheral nervecan be shown to express class II human majorhistocompatibility (HLA) antigens in appropri-ate circumstances.38 Adhesion molecules suchas intercellular cell adhesion molecule(ICAM)39 and vascular cell adhesion molecule(VCAM) (S Hughes, 2000, personal commu-nication) are expressed by endothelium in sec-tions of nerve biopsy material, pointing to arole for T cells. Furthermore, the antiganglio-side antibodies in serum from patients withGuillain Barré syndrome are usually of theIgG1 or IgG3 isotype, which is characteristic ofa T helper type 2 (Th2) dependent antibodyresponse.40

Non-classic T cell responses from ãä T cellsmay play a role because such cells have beenisolated from peripheral nerve in culture41 andcan be detected in nerve section in GuillainBarré syndrome by immunohistochemistry (JCooper et al, 2000, personal communication).Such T cells are restricted by CD1, which hasalso been detected in Guillain Barré syndromebiopsy samples.42 The role of T cell help inantibody production remains to be defined andis the subject of continued research interest.

TreatmentThe mainstay of treatment of Guillain Barrésyndrome remains good intensive care, withrespiratory support where required and earlyrecognition of respiratory failure. The routineuse of prophylaxis for deep venous thrombosisis generally accepted, although it has neverbeen subjected to controlled trial. Positivepressure ventilation with frequent turning toavoid atelectasis and frequent physiotherapy

are also useful. Passive limb movement helps toprevent contractures that hinder rehabilitation.

Several specific attempts at treatment havebeen tried. Unlike the more chronic disorder,chronic inflammatory demyelinating polyneu-ropathy, Guillain Barré syndrome has not beenshown to respond to treatment with oral orintravenous steroids.43 Several controlled clini-cal trials have shown that both plasmaexchange and intravenous immunoglobulinshorten the time to recovery when used in theearly stages of the neuropathy.44–47 In the largeststudy of plasma exchange carried out in NorthAmerica, this procedure improved the time toachieve walking unaided by 32 days.45 Whereasplasma exchange clearly removes a blood bornesubstance mediating the neuropathy, possiblyan antibody, the mechanism of action of intra-venous immunoglobulin administration ismore complicated. This probably includesblockage of Fc receptors, increased catabolismof autoimmune immunoglobulin, and possibleroles in providing anti-idiotypic antibodies andin promoting remyelination.

PrognosisStudies of outcome in Guillain Barré syndromesuggest that at the end of one year from onset ofthe neuropathy 65% of patients achieve analmost complete cure so that they regain theability to perform manual work.48 Of the 35%who do not, about 8% will die in the acutestage,48 usually from cardiac arrhythmias orpulmonary emboli.

Unfortunately, these figures of persistentdeficit have not been significantly altered by theadvent of plasma exchange and intravenousimmunoglobulin, which mainly reduce thetime taken to recover and not the percentage ofpatients making a good recovery. It seems likelythat the proportion of patients with extensiveaxonal damage following the acute phase of thedisease is not altered by present forms of treat-ment. Clearly, further and better treatments areneeded for this group. There is interest in theuse of nerve growth factors. Trials are underway to examine a combined role for steroidsand intravenous immunoglobulin, â-interferontreatment, and repeated courses of intravenousimmunoglobulin. There are also those whofavour immunoabsorption rather than simpleplasma exchange.49 At the moment all theseforms of treatment are experimental.

ConclusionMuch has been learned about the mechanismof neuropathy in Guillain Barré syndrome buttreatment remains disappointing after themajor advances that occurred in the 1980s.Better and more specific treatments are clearlyneeded. It is hoped that recent advances in ourunderstanding of pathogenesis may lead tobetter treatments in the next few years.

1 Guillain G, Barré J, Strohl A. Sur un syndrome de radiculo-nevrite avec hyperalbuminose du liquide cephalorachidiensans reaction cellulaire. Remarques sur les characteresclinique et graphique des reflexes tendinaux. Bulletins etMemories de la Societe Medicale des Hopitaux de Paris1916;40:1462–70.

2 Alter M. The epidemiology of Guillain-Barré syndrome.Ann Neurol 1990:27(suppl):S7–12.

384 Winer

www.molpath.com

on 1 Septem

ber 2018 by guest. Protected by copyright.

http://mp.bm

j.com/

Mol P

ath: first published as 10.1136/mp.54.6.381 on 1 D

ecember 2001. D

ownloaded from

3 Kaplan JE, Katona P, Hurwitz ES, et al. Guillain-Barré syn-drome in the United States, 1979–1980 and 1980–1981.Lack of an association with influenza vaccination. JAMA1982;248:698–700.

4 Carpo M, Pedotti R, Allaria S, et al. Clinical presentationand outcome of Guillain-Barré and related syndromes inrelation to anti-ganglioside antibodies. J Neurol Sci1999;168:78–84.

5 Yuki N. Molecular mimicry between gangliosides andlipopolysaccharides of Campylobacter jejuni isolated frompatients with Guillain-Barré syndrome and Miller Fishersyndrome. J Infect Dis 1997;176(suppl 2):S150–3.

6 Asbury AK, Arnason BG, Karp HR, et al. Criteria for thediagnosis of Guillain-Barré syndrome. Ann Neurol 1978;3:565–6.

7 Asbury AK, Cornblath DR. Assessment of current diagnos-tic criteria for Guillain-Barré syndrome [see comments].Ann Neurol 1990;27(suppl):S21–4.

8 Hughes R. Guillain-Barré syndrome. London: Springer-Verlag, 1990.

9 Winer JB, Hughes RA, Anderson MJ, et al. A prospectivestudy of acute idiopathic neuropathy. II. Antecedent events.J Neurol Neurosurg Psychiatry 1988;51:613–18.

10 Vriesendorp FJ, Mishu B, Blaser MJ, et al. Serum antibod-ies to GM1, GD1b, peripheral nerve myelin, andCampylobacter jejuni in patients with Guillain-Barrésyndrome and controls: correlation and prognosis [seecomments]. Ann Neurol 1993;34:130–5.

11 Mishu B, Ilyas AA, Koski CL, et al. Serologic evidence ofprevious Campylobacter jejuni infection in patients withthe Guillain-Barré syndrome. Ann Intern Med 1993;118:947–53.

12 Jacobs BC, Rothbarth PH, van der Meche FG, et al. Thespectrum of antecedent infections in Guillain-Barrésyndrome: a case–control study. Neurology 1998;51:1110–15.

13 Rees JH, Gregson NA, Hughes RA. Anti-ganglioside GM1antibodies in Guillain-Barré syndrome and their relation-ship to Campylobacter jejuni infection. Ann Neurol1995;38:809–16.

14 Dowling PC, Cook SD. Role of infection in Guillain-Barrésyndrome: laboratory confirmation of herpesviruses in 41cases. Ann Neurol 1981;9(suppl):44–55.

15 Langmuir AD, Bregman DJ, Kurland LT, et al. Anepidemiologic and clinical evaluation of Guillain-Barrésyndrome reported in association with the administrationof swine influenza vaccines. Am J Epidemiol 1984;119:841–79.

16 Toro G, Vergara I, Roman G. Neuroparalytic accidents ofantirabies vaccination with suckling mouse brain vaccine.Clinical and pathologic study of 21 cases. Arch Neurol1977;34:694–700.

17 Ho TW, Hsieh ST, Nachamkin I, et al. Motor nerve termi-nal degeneration provides a potential mechanism for rapidrecovery in acute motor axonal neuropathy after Campylo-bacter infection [see comments]. Neurology 1997;48:717–24.

18 Hariharan H, Naseema K, Kumaran C, et al. Detection ofCampylobacter jejuni/C.coli infection in patients withGuillain-Barré syndrome by serology and culture. NewMicrobiol 1996;19:267–71.

19 Asbury AK, Arnason BG, Adams RD. The inflammatorylesion in idiopathic polyneuritis. Its role in pathogenesis.Medicine 1969;48:173–215.

20 Prineas JW. Pathology of the Guillain-Barré syndrome. AnnNeurol 1981;9(suppl):6–19.

21 Lampert P. Mechanism of demyelination in experimentalallergic neuritis. Electron microscopic studies. Lab Invest1969;20:127–38.

22 Hadden RD, Comblath DR, Hughes RA, et al. Electrophysio-logical classification of Guillain-Barré syndrome: clinicalassociations and outcome. Plasma exchange/SandoglobulinGuillain-Barré syndrome trial group. Ann Neurol 1998;44:780–8.

23 Ho TW, Willison HJ, Nachamkin I, et al. Anti-GD1aantibody is associated with axonal but not demyelinatingforms of Guillain-Barré syndrome. Ann Neurol 1999;45:168–73.

24 Kimura J. Proximal versus distal slowing of motor nerveconduction velocity in the Guillain-Barré syndrome. AnnNeurol 1978;3:344–50.

25 Melnick S. 38 cases of the Guillain-Barré syndrome; animmunological study. BMJ 1963;1:368–73.

26 Koski CL, Humphrey R, Shin ML. Anti-peripheral myelinantibody in patients with demyelinating neuropathy: quan-titative and kinetic determination of serum antibody bycomplement component 1 fixation. Proc Natl Acad Sci U SA 1985;82:905–9.

27 Gregson NA, Koblar S, Hughes RS. Antibodies to ganglio-sides in Guillain-Barré syndrome: specificity and relation-ship to clinical features [see comments]. Q J Med 1993;86:111–17.

28 Kusunoki S. Antiganglioside antibodies in the pathogenesisof autoimmune neuropathies. Rinsho Shinkeigaku 1999;39:93–5.

29 Chiba A, Kusunoki S, Obata H, et al. Serum anti-GQ1b IgGantibody is associated with ophthalmoplegia in MillerFisher syndrome and Guillain-Barré syndrome: clinicaland immunohistochemical studies. Neurology 1993;43:1911–17.

30 Willison HJ, Veitch J, Paterson G, et al. Miller Fishersyndrome is associated with serum antibodies to GQ1bganglioside. J Neurol Neurosurg Psychiatry 1993;56:204–6.

31 Dalakas MC, Quarles RH. Autoimmune ataxic neuropa-thies (sensory ganglionopathies): are glycolipids theresponsible autoantigens. Ann Neurol 1996;39:419–22.

32 Goodyear CS, O’Hanlon GM, Plomp JJ, et al. Monoclonalantibodies raised against Guillain-Barré syndrome-associated Campylobacter jejuni lipopolysaccharides reactwith neuronal gangliosides and paralyze muscle-nervepreparations. J Clin Invest 1999;104:697–708.

33 Chiba A, Kusunoki S, Obata H, et al. Ganglioside composi-tion of the human cranial nerves, with special reference topathophysiology of Miller Fisher syndrome. Brain Res1997;745:32–6.

34 Plomp JJ, Molenaar PC, O’Hanlon GM, et al. Miller Fisheranti-GQ1b antibodies: alpha-latrotoxin-like eVects onmotor end plates [published erratum appears in Ann Neu-rol 1999;45:823]. Ann Neurol 1999;45:189–99.

35 Gabriel C, Gregson N, Hughes R. Anti-PMP22 antibodiesin patients with inflammatory neuropathy. J Neuroimmunol2000;104:139–46.

36 Hughes RA, Gray IA, Gregson NA, et al. Immune responsesto myelin antigens in Guillain-Barré syndrome. J Neuroim-munol 1984;6:303–12.

37 Hartung HP, Hughes RA, Taylor WA, et al. T cell activationin Guillain-Barré syndrome and in MS: elevated serumlevels of soluble IL-2 receptors. Neurology 1990;40:215–18.

38 Pollard JD, Baverstock J, McLeod JG. Class II antigenexpression and inflammatory cells in the Guillain-Barrésyndrome. Ann Neurol 1987;21:337–41.

39 Putzu G, Figarella-Branger D, Bouvier-Labit C, et al.Immunohistochemical localization of cytokines, C5b-9 andICAM-1 in peripheral nerve of Guillain-Barré syndrome. JNeurol Sci 2000;174:16–21.

40 Ogino M, Orazio N, Latov N. IgG anti-GM1 antibodiesfrom patients with acute motor neuropathy are predomi-nantly of the IgG1 and IgG3 subclasses. J Neuroimmunol1995;58:77–80.

41 Ben-Smith A, Gaston JS, Barber PC, et al. Isolation andcharacterisation of T lymphocytes from sural nervebiopsies in patients with Guillain-Barré syndrome andchronic inflammatory demyelinating polyneuropathy. JNeurol Neurosurg Psychiatry 1996;61:362–8.

42 Khalili-Shirazi A, Gregson N, Hughes R. CD1 expression inhuman peripheral nerve of GBS patients. Biochem Soc Trans1997;5:172S.

43 Hughes R, van der Meche FG. Corticosteroids for treatingGuillain-Barré syndrome. Cochrane Database Syst Rev2000;2:CD001446.

44 The Guillain-Barré Syndrome Study Group. Plasmapher-esis and acute Guillain-Barré syndrome. Neurology 1985;35:1096–104.

45 French Cooperative Group on Plasma Exchange inGuillain-Barré Syndrome. EYciency of plasma exchange inGuillain-Barré syndrome: role of replacement fluids. AnnNeurol 1987;22:753–61.

46 van der Meche FG, Schmitz PI. A randomized trialcomparing intravenous immune globulin and plasmaexchange in Guillain-Barré syndrome. Dutch Guillain-Barré study group [see comments]. N Engl J Med1992;326:1123–9.

47 Plasma Exchange/Sandoglobulin Guillain-Barré SyndromeTrial Group. Randomised trial of plasma exchange,intravenous immunoglobulin, and combined treatments inGuillain-Barré syndrome [see comments]. Lancet 1997;349:225–30.

48 Rees JH, Thompson RD, Smeeton NC, et al. Epidemiologi-cal study of Guillain-Barré syndrome in south east England[see comments]. J Neurol Neurosurg Psychiatry 1998;64:74–7.

49 Watanabe T, Matsuura O, Natsume J, et al. Dramaticimprovement with immunoabsorption therapy in a 7-year-old girl with severe Guillain-Barré syndrome after unsuc-cessful gammaglobulin therapy. No To Hattatsu 1998;30:255–60.

Guillain Barré syndrome 385

www.molpath.com

on 1 Septem

ber 2018 by guest. Protected by copyright.

http://mp.bm

j.com/

Mol P

ath: first published as 10.1136/mp.54.6.381 on 1 D

ecember 2001. D

ownloaded from