SECTION EDITOR: CHRISTOPHER G. GOETZ, MD

Guillain-Barre SyndromeMichel Bonduelle, MD, Paris VI University, Paris, France

I n 1859, Landry1 described the clinical features of acute ascending weakness withoutamyotrophy. Other 19th-century clinical descriptions followed, but the full extent of themotor polyradiculoneuritis and the characteristic albuminocytologic dissociation in thecerebrospinal fluid was only described in 1916 by Guillain, Barre, and Strohl.2 Guillain

(1876-1961), who eventually held Charcot’s Professorial Chair at the Salpietriere in Paris,France, encountered the syndrome in soldiers while he was chief staff physician for the SixthArmy Neurological Center at the North front in France. Over the subsequent 20 years, morethan 30 such cases were documented in the international medical literature to which Guillain3

himself added 10 cases in his follow-up article of 1936. The condition became known interna-tionally under the rubric Guillain-Barre syndrome (GBS). Although the condition was originallysuspected to be infectious in nature, the distinctive pathological features led to hypotheses ofimmunological origin. This article cites seminal views on the syndrome and traces historicaldevelopments up to the time of Guillain’s death in 1961.

EARLY REFERENCES

In the “progressive diffuse” paralyses, the ini-tially restricted area of paralysis gradually en-larges from its origin. This proximal propaga-tion may be stepwise and orderly, as in theextensoprogressive ascending paralysis . . . or in-termittent and random. . . . In the former, whichis of some importance, the symptoms start in thedistal extremities,progressproximallyandcepha-lad and become more intense with each area af-fected. . . . Although almost always slowly evolv-ing, it may also progress with extreme rapidityand be serious or even fatal.

Landry, 18591

If we may draw any deductions from the ill-defined data which we at present possess con-cerning Landry’s paralysis, it may be distin-guished from acute myelitis by the slightdisturbances of sensation, the preservation of theelectrical excitability of muscles, the absence ofmotor irritation and of trophic disturbances.

Osler and Sidell, 19604

FULL CLINICAL DESCRIPTION

We call attention to a clinical syndrome whichwe have observed in 2 cases, a syndrome char-acterized by motor disturbances, loss of deeptendon reflexes, preservation of cutaneous re-flexes, paresthesias with slight disturbance ofobjective sensibility, tenderness on pressure of

the muscles, little change in the electrical re-actions of the nerves or muscles and notewor-thy hyperalbuminosis of the cerebrospinal fluidin the absence of cytologic reaction (albumino-cytologic dissociation). This syndrome seemsto us the result of a concomitant attack on thespinal roots, nerves and muscles, probably byan infectious or toxic agent. It must be differ-entiated from simple radiculitis, pure polyneu-ritities, and polymyositis. Graphic studies ofthe speed of the reflexes and their latent timeand of the character of the muscular contrac-tions demonstrate that the entire neuromus-cular apparatus participates in the syndrome.

Guillain et al, 19162

ADDITIONAL FEATURESAND CLINICAL VARIANTS

Ataxia

“In several instances . . . , I observed the pres-ence of ataxia which has been noted also byother authors. Some patients may present withpseudotabetic appearance like that associatedwith diphtheric neuritis.”

Guillain, 19537

Cranial Nerve Involvement

The facial nerve appears to be especially suscep-tible. The paralysis is of peripheral type and usu-

HISTORY OF NEUROLOGY: SEMINAL CITATIONS

ARCH NEUROL / VOL 55, NOV 19981483

©1998 American Medical Association. All rights reserved.Downloaded From: http://archneur.jamanetwork.com/ by a Queen Mary, University of London User on 06/05/2014

ally slight and transitory and disappearscompletely. . . . Diplopia due to paraly-sis of ocular muscles is relatively rare-. . . . Involvement of the trigeminal, glos-sopharyngeal, vagus, spinal accessory andhypoglossal nerves is uncommon.

Guillain, 19363

Three cases characterized by total exter-nal ophthalmoplegia, ataxia, and loss oftendon reflexes are presented. . . . The ce-rebrospinal fluid showed albuminocyto-logic dissociation. The syndrome provesto be a variant of acute inflammatory poly-neuritis (the Guillain-Barre type of poly-neuropathy) in which limb involvementwas minimal or absent.

Fisher, 19775

Autonomic Involvement

The major bulbar disturbances, withchanges in phonation, swallowing andrespiratory and cardiac rhythm are ex-ceptional; they are transitory and dis-appear completely.

Guillain, 19363

Natural History and Prognosis

Initially, Guillain felt that the dis-ease was benign but his later experi-ence and that of van Bogaert6 led himto appreciate fatal forms, especially ifdysautonomia was not controlled.

The prognosis does not appear to be ex-tremely serious, if we may judge fromthe course of the disease in our two pa-tients; the first had almost recovered andthe second was improving when theywere discharged from the army.

Guillain et al, 19162

[The disease] would probably have beenreversible and curable if we could havesustained the patient for a few hours ordays.

Guillain, 19537

Cytoalbuminic Dissociation

Guillaincontributed fundamentally tothe use of cerebrospinal fluid analy-sis in the diagnosis of GBS, demon-strating the importance of the find-ing in the proper clinical context, butalways conscious that the finding hadno specificity in isolation.

We place special emphasis on the acel-lular hyperalbuminosis of the cerebro-spinal fluid, an observation, as far as we

know, that has not previously been de-scribed in similar cases.

Guillain et al, 19162

Isolated cytoalbumic dissociation with-out the other clinical elements of the syn-drome has absolutely no diagnosticvalue.

Guillain, 19537

Etiologic and PathologicalFeatures and Pathogenesis

Guillain studied GBS throughout hiscareer and conducted a number oflaboratory studies aimed at definingan infectious cause. Although unsuc-cessful, he held to this hypothesiseven in his last treatise before retire-ment. Haymaker and Kernohan8 pro-vided a landmark pathological de-scription of GBS with their review of50 cases, some of them later con-tested by Guillain3 as leading to “to-tal nosographic confusion.” “They[Haymaker and Kernohan] empha-sized demyelination and edema butfelt that lymphocytosis and inflam-mation were late events.” After Guil-lain’s death, Asbury and colleagues9

described multifocal lymphocytic in-filtration at the radicular level andsuggested that lymphocytes had a pri-mary role in the syndrome pathogen-esis. Waksman and Adams10 empha-sized the similaritiesbetweenGBSandexperimental allergic neuritis, therebyproviding a working model of the ill-ness. Immunological hypotheses uni-fied idiopathic, postviral, postvac-cinial, and secondary Campylobacterjejuni forms of GBS.

In 1953 Guillain7 remarked thatGBS was a special infection, whichlike so many other, is of unknownorigin.

The most profound alterations were en-countered in the peripheral nervous sys-tem. The earliest change consisted of ede-ma. . . . At the 5-day stage, myelin sheathand axis cylinder changes were readily vis-ible. In none of the early cases was thereany local cellular reaction or inflamma-tory exudate. . . . Lymphocytes whichtended in some cases to increase in num-ber as time went on, were regarded as partof the reparative process.

Haymaker and Kernohan, 19498

[We] describe a disease in rabbits pro-duced by the inoculation of homolo-gous or heterologous sciatic nerve withthe usual adjuvant . . . called ... experi-mental allergic neuritis (EAN). The le-sions are confined to the nerve roots, spi-nal ganglia and peripheral nerves. Thereis characteristic change in the cerebro-spinal fluid consisting of an elevation ofprotein without pleocytosis (albumino-cytologic dissociation). We believe thisnew experimental disease to be ofimportance because it represents one ofthe first laboratory models of non-infectious inflammatory disease of pe-ripheral nerves. Moreover, it bears cer-tain resemblances to a group of humandiseases known by the terms “acute in-fectious polyneuritis,” “Guillain-Barresyndrome” and “Landry’s paralysis.”

Waksman and Adams, 19559

Accepted for publication November 26,1997.

Reprints: Michel Bonduelle, MD,15 Boulevard des Invalides, 75007Paris, France.

REFERENCES

1. Landry J-B. Note sur la paralysie ascendante aigue.Gaz Hebd Med Chir. 1859;6:472-474.

2. Guillain G, Barre JA, Strohl A. Sur un syndromede radiculo-nevrite avec hyperalbuminose du liq-uide cephalo-rachidien sans reaction cellulaire: re-marques sur les caracteres cliniques et graphiquesdes reflexes tendineux. In: Bulletins et Memoiresde la Societe Medicale des Hopitaux de Paris. Paris,France: Masson et Cie; 1916: 1462-1470.

3. Guillain G. Radiculoneuritis with acellular hyper-albuminosis of the cerebrospinal fluid. Arch Neu-rol Psychiatry. 1936;36:975-990.

4. Osler LD, Sidell AD. The Guillain-Barre syn-drome: the need for exact diagnostic criteria.N Engl J Med. 1960;262:964-969.

5. Fisher JR. Guillain-Barre syndrome following or-ganophosphate poisoning. JAMA. 1977;238:1950-1951.

6. van Bogaert L. Note preliminaire sur un groupede cas de poly-radiculo-nevrite avec dissociationalbumino-cytologique (type Guillain et Barre).J Belge Neurol Psych. 1937;37:718-720.

7. Guillain G. Considerations sur le syndrome de Guil-lain-Barre. Ann Med Interne. 1953;54:2, 81-149.

8. Haymaker W, Kernohan JW. The Landry-Guillain-Barre syndrome: clinicopathologic report of fiftyfatal cases and a critique of the literature. Medi-cine (Baltimore). 1949;28:59-141.

9. Asbury AK, Arnason BG, Adams RD. The inflam-matory lesions in idiopathic polyneuritis. Medi-cine. 1969;48:173-215.

10. Waksman BH, Adams RD. Allergic neuritis: an ex-perimental disease of rabbits induced by the in-jection of peripheral nervous tissue and adju-vants. J Exp Med. 1955;102:213-235.

ARCH NEUROL / VOL 55, NOV 19981484

©1998 American Medical Association. All rights reserved.Downloaded From: http://archneur.jamanetwork.com/ by a Queen Mary, University of London User on 06/05/2014