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Guillain-Barré syndromeGuillain-Barré syndrome is the most common cause ofacute flaccid paralysis. Its annual incidence is 1–2 per100 000 population and frequency rises with advancingage. Patients with this disorder present with rapidlyprogressive tingling, numbness, weakness, and sometimespain. Weakness can be distal, proximal, or both. Tendonreflexes are lost early. Patients can have facial and bulbarweakness and sometimes ophthalmoplegia. Theprogressive phase usually lasts about 2 weeks but can beas long as 4 weeks. Gradual recovery begins after a fewdays or weeks and continues over several months.

Diagnosis is usually clear from the clinical picture.Concentration of cerebrospinal fluid protein can benormal but it is usually raised after the first week. TheCSF cell count remains normal. Neurophysiological testsconfirm the presence of a peripheral neuropathy. Nerve

Lancet 2004; 363: 2186–88

Department of Clinical Neurosciences, Guy’s Hospital, Guy’s,King’s & St Thomas’ School of Medicine, London SE1 1UL, UK(J Pritchard BM BCh, Prof R Hughes MD)

Correspondence to: Jane Pritchard(e-mail: jane.pritchard@kcl.ac.uk)

conduction velocities are usually slowed and there ispartial conduction block indicating demyelination, so theunderlying substrate is judged an acute inflammatorydemyelinating polyradiculoneuropathy. In about 5% ofpatients in most European and North American series,action potentials are reduced but conduction velocities arenormal, suggesting an axonal neuropathy affecting purelymotor (acute motor axonal neuropathy) or motor andsensory (acute motor and sensory axonal neuropathy)nerves. When nerves are not excitable, to distinguishbetween acute inflammatory demyelinating polyradicu-loneuropathy and acute motor axonal neuropathy isimpossible without doing a nerve biopsy.

PathogenesisIn acute inflammatory demyelinating polyradiculo-neuropathy, the peripheral nerve and spinal roots areinitially infiltrated by T lymphocytes and macrophages.

Guillain-Barré syndrome

Jane Pritchard, Richard A C Hughes

Case reportA man aged 52 years had a short diarrhoeal illness followed6 days later by rapidly ascending paraesthesiae and limbweakness. His weakness worsened so that he neededassisted ventilation. He had normal cognition, extraocularmovements, and facial muscles, but pronounced weaknessof neck flexion and all four limbs. After 3 days he wasvirtually paralysed and needed ventilation. Tendon reflexeswere absent. Sensation was intact.

The cerebrospinal fluid protein was 500 mg/L and cellcount was normal on the first day of neurologicalsymptoms. On day 5, his nerves were not excitable. His serum contained IgG and IgM antibodies againstganglioside GM1. Nerve biopsy undertaken on day 10showed prominent axonal degeneration without demyelination, consistent with a diagnosis of the acutemotor and sensory axonal neuropathy form of Guillain-Barrésyndrome.

The patient was given intravenous immunoglobulin. Hereceived a percutaneous tracheostomy and was ventilatedfor 6 months. He was fed via a percutaneousgastroenterostomy and stayed in hospital for 12 months. 1 year after onset, he was still chair-bound, could only lifthis shoulders and flex his fingers slightly, and had severeweakness of his hips and knees and paralysed ankles. Hehas gradually improved, and 8 years later can walk 10 yardswith a frame. His hands remain weak, so activities of dailyliving such as doing buttons or holding a knife and forkremain difficult.

Figure 1: Jean-Baptiste Octave Landry de Thézillat(1826–1865)Reprinted from reference 4 with permission.

Eponym

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intensive care during the acute phase is essential. Despitemodern treatment and intensive care, Guillain-Barrésyndrome still carries 5% mortality, and 15% of patientsneed aid to walk after a year. Although substantialrecovery is the rule, continued fatigue can be a drawback.

Historical aspectsThe first description of Guillain-Barré syndrome hasbeen suggested to be by Jean Baptiste Octave Landry deThézillat (1826–65; figure 1) in 1859, under the titleacute ascending paralysis.3 However, Landry’s ascendingparalysis came to be regarded as a so-called dustbindiagnosis covering a range of entities, including acutemyelitis and peripheral neuritis.3 Landry was born inLimoges, studied in Paris, and published several articlesas a young neurologist. His seminal paper on ascendingparalysis3 was his last before he was overtaken by thetemptation of private practice at a spa in Auteuil. Heassisted with caring for patients with cholera but died ofthe disease himself at the age of 39 years, despite theattention of none less than Charcot.4

In October, 1916, Georges Guillain (figure 2), Jean-Alexandre Barré (figure 3), and André Strohl (figure 4)presented a paper to a meeting of the Paris hospitalsabout two soldiers who had recovered from an acuteparalysing illness.5 From graphical records showingreduced and delayed tendon reflexes, with a latency ofalmost twice normal, they deduced that nerveconduction or the central part of the reflex was impaired.They applied the technique of lumbar puncturedescribed 25 years previously and showed thatcerebrospinal fluid protein concentration was raised butcell count normal. This occurrence of albumino-cytological dissociation was then used to help distinguishGuillain-Barré syndrome from poliomyelitis and otherdisorders.

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Macrophages invade and strip off myelin sheaths. Inmild cases, axons are left intact and becomeremyelinated. In severe cases, axons degenerate as well.In acute motor axonal neuropathy, antibody toganglioside antigens and complement attach to theaxolemma, and macrophages invade the axon directly,initially leaving the myelin sheath intact.

Two-thirds of patients report symptoms of an infectionin the weeks preceding Guillain-Barré syndrome.Epidemiological evidence lends support to associationswith Campylobacter jejuni, Mycoplasma pneumoniae,cytomegalovirus, and Epstein-Barr virus, but otherinfections are probably also occasional precipitants.Despite the multiplicity of antecedent infections, thepopular hypothesis invokes crossreactivity betweenmicrobial and myelin antigens to account for the disease.The capsule of C jejuni contains lipopolysaccharide, withantigenic epitopes resembling those on gangliosides inperipheral nerve. 95% of patients with the Miller Fishervariant of Guillain-Barré syndrome (consisting ofophthalmoplegia, areflexia, and ataxia) have antibodiesdirected against ganglioside GQ1b. In acute motoraxonal neuropathy, many patients have antibodies togangliosides GD1a, GM1, and GalNacGD1a, which arepresent on the axolemma.1 However, acute inflammatorydemyelinating polyradiculoneuropathy does not have astrong association with antibodies to ganglioside.According to an alternative hypothesis, T-cell-mediatedimmunity against myelin antigens is the majormechanism, as in the animal model, experimentalautoimmune neuritis.2

TreatmentIntravenous immunoglobulin hastens recovery as muchas plasma exchange, the previous gold standard.Surprisingly, steroids are not effective. Excellent

Figure 2: Georges Guillain (1876–1961)Reprinted from reference 6 with permission.

Figure 3: Jean-Alexandre Barré (1880–1967)8

Reprinted with permission of F Rohmer.

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Georges Guillain (1876–1961)Guillain (figure 2) succeeded Pierre Marie as professor ofneurology at Salpêtrière Hospital in Paris in 1923, 7 yearsafter his description of Guillain-Barré syndrome. Hesubsequently noted that patients might have ataxia andcranial nerve involvement, heralding the later descriptionof the Miller Fisher syndrome.

Guillain published on a wide range of subjects and hasgiven his name to several eponymous syndromes, many ofwhich are not widely used in medical terminology today.6

He was succeeded by Alajouanine in 1947, with whom hedescribed the Guillain-Alajouanine-Garcin syndrome ofextensive unilateral cranial nerve palsies, usually due tomalignant disease in the nasopharynx or skull base.

Draganescu and Claudian introduced the termGuillain-Barré syndrome at a meeting of the Société deNeurologie de Paris, chaired by Barré in 1927.7 The nameof Strohl, who undertook electrical recordings, wasomitted from the title of the paper and, even moreunfairly, from the reference to the original work.

Jean-Alexandre Barré (1880–1967)Barré (figure 3) came from near Nantes in Brittany, wasintern to Babinski in Paris, and became professor ofneurology in Strasbourg from 1919 until 1950.8 Hepublished many papers on various subjects, including thesyndrome of neck pain and dizziness due to arthritic ortraumatic damage to the cervical spine, called Barré-Liéouor cervicosympathetic syndrome. Despite a cerebro-vascular accident 14 years before his death, he continuedto participate in neurological meetings.

André Strohl (1887–1977)Strohl (figure 4) came from Poitiers and initially studiedmedicine before changing to study maths, physics, andchemistry. He returned to medicine, obtained his doctoralthesis in medicine, and subsequently gained a seconddoctorate in physics. With hindsight, his recordings of thedelayed tendon reflexes foretold presence of demyelin-ation as the major neurophysiological abnormality in theacute inflammatory demyelinating polyradiculoneuro-pathy form of Guillain-Barré syndrome. He publishedextensively on reflexes and nerve conduction and wasprofessor of physical medicine in Paris from 1925 until heretired in 1957.9

Conflict of interest statementNone declared.

AcknowledgmentsWe thank our patient for allowing us to publish his history andProf Michel Bonduelle for reading the manuscript.

References1 Willison HJ, Yuki N. Peripheral neuropathies and anti-glycolipid

antibodies. Brain 2002; 125: 2591–25.2 Hughes RAC, Gregson NA, Hadden RDM, Smith KJ. Pathogenesis

of Guillain-Barré syndrome. J Neuroimmunol 1999; 100: 74–97.3 Landry O. Note sur la paralysie ascendante aiguë.

Gaz Hebdomadaire Méd Chir 1859; 6: 472–88.4 Haymaker WE. Jean-Baptiste Octave Landry de Thézillat. The

founders of neurology: 133 biographical sketches. Springfield:Charles C Thomas, 1953: 320–23.

5 Guillain G, Barré JA, Strohl A. Sur un syndrome de radiculo-névrite avec hyperalbuminose du liquide céphalo-rachidiensans réaction cellulaire: remarques sur les caractères cliniques etgraphiques des réflexes tendineux. Bull Soc Méd Hôp Paris 1916;40: 1462–70.

6 Bonduelle M. Georges Guillain. Revue Neurol (Paris) 1977; 133:661–66.

7 Draganescu S, Claudian J. Sur un cas de radiculo-névrite curable(syndrome de Guillain-Barré) apparue au cours d’une ostéomyelitedu bras. Revue Neurol (Paris) 1927; 2: 517–19.

8 Rohmer F. Jean-Alexandre Barré (1880–1967). L’homme, sa vie etson oeuvre. Conférences de l’Institut d’Histoire de la Médecine deLyon 1984. Cycle 1983–1984: 185–207.

9 Green D. Infectious polyneuritis and Professor André Strohl: a historical note. N Engl J Med 1962; 267: 821–22.

Figure 4: André Strohl (1887–1977)Reprinted from reference 9 with permission from Massachusetts MedicalSociety.

Rights were not granted to include thisimage in electronic media. Please refer

to the printed journal.

For personal use. Only reproduce with permission from The Lancet.