Background

This is an inflammatory disorder of the peripheral nerves and is characterized by the rapid onset of weakness with paralysis of the legs, arms, breathing muscles and face. In severe cases, patients may be paralyzed, necessitating ventilatory assist. Most people recover but the length of the illness is unpredictable and may last months.

OUTLINE

Epidemiology
Disease Associations	Campylobacter infection Cytomegalovirus infection
Pathogenesis	Ganglioside antibodies
Gross Appearance and Clinical Variants	Acute motor neuropathy Fulminant disease Miller-Fisher Syndrome
Histopathological Features and Variants
Laboratory/Radiologic/Other Diagnostic Testing	Anti-ganglioside antibodies
Special Stains/ Immunohistochemistry /Electron Microscopy
Differential Diagnosis	Alcohol
Prognosis and Treatment	Gabapentin
Commonly Used Terms
Internet Links

 

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Acute inflammatory demyelinating polyneuropathy Landry's ascending paralysis
INCIDENCE	1-2/100,000 Most common cause of rapidly acquired paralysis
A prospective study on the incidence and prognosis of Guillain-Barre syndrome in Emilia-Romagna region, Italy (1992-1993). Emilia-Romagna Study Group on Clinical and Epidemiological Problems in Neurology.	Neurology 1997 Jan;48(1):214-21 Abstract quote We performed a multicenter prospective study on the incidence and prognosis of Guillain-Barre syndrome (GBS) in the Emilia-Romagna region (3,909,512 inhabitants), Italy, over a 2-year period (1992-1993). The case finding method was based on a surveillance system including neurologic departments, all private and public general hospitals, and all practicing neurologists. We also reviewed all the ICD codes of hospital discharges. Ninety-four patients with GBS were identified, giving a mean incidence rate of 1.20 per 100,000 per year. Men/women ratio was 1.94. Incidence rate increased with age for both sexes. There were no significant incidence variations among seasons or months. Antecedent infections were reported in 59% of the patients. There was an overall good prognosis. After 6 months, 64% of patients had recovered and only 4% was still severely disabled. Acute mortality was 3%. Older age was the strongest predictor of poor outcome.

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
CAMPYLOBACTER JEJUNITIS
Fulminant Guillain-Barre syndrome after Campylobacter jejuni enteritis and monospecific anti-GT1a IgG antibody. Okuda B, Koga M, Katsuta T, Okamoto K, Yuki N. Department of Neurology, Ehime Prefectural Central Hospital, Matsuyama.	Intern Med 2002 Oct;41(10):889-91 Abstract quote A 21-year-old man developed rapid progression of tetraplegia, bulbar palsy, and respiratory paralysis after Campylobacterjejuni enteritis. Based on the diagnosis of Guillain-Barre syndrome, he received plasmapheresis and intravenous immunoglobulin. Serum anti-GT1a IgG antibody which lacked cross-reactivity with GQ1b was detected. Four months after the onset, the patient still had severe muscle weakness of the lower limbs. This case suggests that anti-GT1a IgG antibody can be associated with severe paralysis in Guillain-Barre syndrome after C. jejuni enteritis.
Incidence of Guillain-Barre syndrome following infection with Campylobacter jejuni. McCarthy N, Giesecke J. Swedish Institute for Infectious Disease Control, SE-171 82, Solna, Sweden.	Am J Epidemiol 2001 Mar 15;153(6):610-4 Abstract quote Evidence of recent or ongoing Campylobacter jejuni infection has been found in approximately one out of every four cases of Guillain-Barre syndrome (GBS). It is increasingly accepted that C. jejuni infection is an important causal factor for GBS. However, the likelihood of GBS' occurring following an episode of C. jejuni gastroenteritis has not been measured. The authors measured the incidence of GBS in a large cohort of persons with laboratory-confirmed C. jejuni infection. Cases of C. jejuni infection were derived from the Swedish national laboratory reporting system for the years 1987--1995. Follow-up for GBS was carried out using the Swedish national hospital inpatient register. Nine cases of GBS were detected in the cohort, which comprised 29,563 cases of C. jejuni infection--a rate of 30.4 per 100,000 (95% confidence interval: 13.9, 57.8). This compares with an expected incidence of 0.3 per 100,000 in a 2-month period in the general population. GBS is an important but rare complication of C. jejuni infection. The risk of developing GBS during the 2 months following a symptomatic episode of C. jejuni infection is approximately 100 times higher than the risk in the general population.
CYTOMEGALOVIRUS
Cytomegalovirus infection and Guillain-Barre syndrome: the clinical, electrophysiologic, and prognostic features. Dutch Guillain-Barre Study Group. Visser LH, van der Meche FG, Meulstee J, Rothbarth PP, Jacobs BC, Schmitz PI, van Doorn PA. Department of Neurology, University Hospital Dijkzigt, Rotterdam, The Netherlands.	Neurology 1996 Sep;47(3):668-73 Abstract quote Guillain-Barre syndrome (GBS) is usually preceded by infections, in particular cytomegalovirus (CMV) and Campylobacter jejuni infection. We studied the clinical and electrophysiologic features of 20 CMV-associated GBS patients and compared the findings with earlier established data of C. jejuni-related GBS patients (n = 43) and of GBS patients without these infections (n = 71). The patients all participated in the Dutch GBS trial in which we compared the effect of intravenous immune globulins and plasma exchange. We demonstrate that CMV-related GBS patients have a different clinical pattern in comparison with the other two GBS groups. They are significantly younger, initially have a severe course indicated by a high frequency of respiratory insufficiency, and often develop cranial nerve involvement and severe sensory loss. This is in contrast to C. jejuni infection, which is associated with motor GBS. Both infections are associated with delayed recovery compared with the GBS patients without these infections.
INFLUENZA VACCINATION
Guillain-Barré syndrome following influenza vaccination. Haber P, DeStefano F, Angulo FJ, Iskander J, Shadomy SV, Weintraub E, Chen RT. Immunization Safety Branch, Epidemiology and Surveillance Division, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Ga 30333, USA.	JAMA. 2004 Nov 24;292(20):2478-81.Abstract quote   CONTEXT: An unexplained increase in the risk of Guillain-Barre syndrome (GBS) occurred among recipients of the swine influenza vaccine in 1976-1977. Guillain-Barre syndrome remains the most frequent neurological condition reported after influenza vaccination to the Vaccine Adverse Events Reporting System (VAERS) since its inception in 1990. OBJECTIVE: To evaluate trends of reports to VAERS of GBS following influenza vaccination in adults. DESIGN, SETTING, AND PARTICIPANTS: VAERS is the US national spontaneous reporting system for adverse events following vaccination. Reports of GBS in persons 18 years or older following influenza vaccination were evaluated for each influenza season from July 1, 1990, through June 30, 2003. The number of people vaccinated was estimated from the National Health Interview Survey and US census data. Beginning in 1994, active follow-up was conducted to verify GBS diagnosis and obtain other clinical details. MAIN OUTCOME MEASURE: Reporting rates of GBS following influenza vaccination over time. RESULTS: From July 1990 through June 2003, VAERS received 501 reports of GBS following influenza vaccination in adults. The median onset interval (13 days) was longer than that of non-GBS reports of adverse events after influenza vaccine (1 day) (P<.001). The annual reporting rate decreased 4-fold from a high of 0.17 per 100,000 vaccinees in 1993-1994 to 0.04 in 2002-2003 (P<.001). A GBS diagnosis was confirmed in 82% of reports. Preceding illness within 4 weeks of vaccination was identified in 24% of reported cases. CONCLUSIONS: From 1990 to 2003, VAERS reporting rates of GBS after influenza vaccination decreased. The long onset interval and low prevalence of other preexisting illnesses are consistent with a possible causal association between GBS and influenza vaccine. These findings require additional research, which can lead to a fuller understanding of the causes of GBS and its possible relationship with influenza vaccine.

 

PATHOGENESIS	CHARACTERIZATION
GANGLIOSIDE ANTIBODIES
Antibodies against gangliosides: a link between preceding infection and immunopathogenesis of Guillain-Barre syndrome. Schwerer B. Department of Neuroimmunology, Brain Research Institute, University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.	Microbes Infect 2002 Mar;4(3):373-84 Abstract quote Autoantibodies against gangliosides GM1 and GQ1b, characteristic cell surface glycolipids of the nervous system, are present in specific clinical types of GuillainBarre syndrome (GBS). Close associations of anti-GM1 with acute motor axonal neuropathy, and of anti-GQ1b with Miller Fisher syndrome, strongly suggest that these antibodies contribute to neuropathy pathogenesis. Immune responses against gangliosides are suspected to originate as a result of molecular mimicry between gangliosides and lipopolysaccharides of Campylobacter jejuni, the most frequent infectious trigger of GBS. Thus, antibodies against gangliosides may link C. jejuni infection with the precipitation of neurological disease.
Fine specificities of anti-LM1 IgG antibodies in Guillain-Barre syndrome. Susuki K, Yuki N, Hirata K, Kuwabara S. Department of Neurology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, 321-0293, Tochigi, Japan.	J Neurol Sci 2002 Mar 30;195(2):145-8 Abstract quote We investigated the prevalence of anti-LM1 IgG antibody and its fine specificity in Guillain-Barre syndrome (GBS). Anti-LM1 IgG and IgM antibodies from sera of 47 patients with GBS--19 with acute inflammatory demyelinating polyneuropathy (AIDP), 27 with acute motor axonal neuropathy (AMAN), and 1 with acute motor-sensory axonal neuropathy (AMSAN)--were tested. Anti-LM1 IgG antibody was detected in only one patient with AIDP, whereas it was present in seven with AMAN and in one with AMSAN. Sera from the eight IgG anti-LM1-positive patients with AMAN/AMSAN also had IgG activity against the gangliosides GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, or GQ1b. Anti-LM1 IgG antibodies from the AMAN/AMSAN patients cross-reacted with other gangliosides, whereas IgG antibody from the AIDP patient was monospecific against LM1. Anti-LM1 IgG antibody therefore, cannot be a marker of AIDP. In addition, whether monospecific anti-LM1 IgG antibody is associated with AIDP remains to be concluded. Larger studies are needed to verify whether monospecific anti-LM1 IgG antibody could be a marker of AIDP.
Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barre syndrome: clinical and immunohistochemical studies. Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Department of Neurology, School of Medicine, University of Tokyo, Japan.	Neurology 1993 Oct;43(10):1911-7 Abstract quote To determine the significance of serum anti-GQ1b IgG antibody, we studied the disease spectrum associated with this antibody and GQ1b epitope in the human nervous system. We examined sera from 19 patients with typical Miller Fisher syndrome (MFS), five patients with acute postinfectious ophthalmoplegia without ataxia (atypical MFS), six patients with Guillain-Barre syndrome (GBS) with ophthalmoplegia (GBS-OP[+]), and 23 patients with GBS without ophthalmoplegia (GBS-OP[-]). We also examined sera from 84 patients with other neurologic or non-neurologic disorders and from 16 normal control subjects. Eighteen of the 19 patients with typical MFS, all the patients with atypical MFS, and five of the six patients with GBS-OP(+) had increased anti-GQ1b IgG activity in ELISA, but none of the patients in the other groups, including GBS-OP(-), had it. All the patients' sera that had anti-GQ1b IgG antibody showed anti-GT1a IgG activity. Results of absorption studies suggested that the same antibody reacted with GQ1b and GT1a. An anti-GQ1b mouse monoclonal antibody immunostained the paranodal regions of the extramedullary portion of the human oculomotor, trochlear, and abducens nerves. Biochemical analysis showed that the human oculomotor nerve contained a larger amount of GQ1b than did the ventral and dorsal roots of the spinal cord. We conclude that serum IgG antibody against GQ1b is very closely associated with acute postinfectious ophthalmoplegia in MFS and GBS.

 

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
Guillain-Barre syndrome: MR imaging findings of the spine in eight patients. Byun WM, Park WK, Park BH, Ahn SH, Hwang MS, Chang JC. Department of Diagnostic Radiology, College of Medicine, Yeungnam University, Namku, Taegu, South Korea.	Radiology 1998 Jul;208(1):137-41 Abstract quote PURPOSE: To evaluate magnetic resonance (MR) imaging findings of the spine in patients with Guillain-Barre syndrome. MATERIALS AND METHODS: MR imaging findings in eight patients (three male, five female; age range, 2-47 years) with Guillain-Barre syndrome were retrospectively reviewed. Guillain-Barre syndrome was diagnosed mainly on the basis of symptoms and also on the basis of supportive ancillary data, such as the results cerebrospinal fluid analysis and electrophysiologic evaluation. In addition, follow-up MR imaging was performed in three patients, who had slight clinical improvement. RESULTS: All patients had thickening of the intrathecal spinal nerve roots and cauda equina, with varying degrees of enhancement on gadolinium-enhanced axial T1-weighted images. Two enhancement patterns were noted. One was enhancement of both the anterior and posterior spinal nerve roots (n = 2); the other was enhancement of the anterior spinal nerve roots only (n = 6). Follow-up MR imaging in the three patients with slight improvement of symptoms revealed that the thickening and the degree of enhancement of the spinal nerve roots were diminished. CONCLUSION: Although the enhancement of the intrathecal spinal nerve roots is not specific to Guillain-Barre syndrome and can be seen in neoplasia and other inflammatory processes, the enhancement of only the anterior spinal nerve roots is strongly suggestive of Guillain-Barre syndrome.
LABORATORY MARKERS
ANTI-GANGLIOSIDE ANTIBODIES
Detection of anti-ganglioside antibodies in Guillain-Barre syndrome and its variants by the agglutination assay. Alaedini A, Briani C, Wirguin I, Siciliano G, D'Avino C, Latov N. Department of Neurology and Neuroscience, Cornell University, 525 E. 68th St., Room LC 807, New York, NY 10021, USA.	J Neurol Sci 2002 Apr 15;196(1-2):41-4 Abstract quote Sera from 40 patients with Guillain-Barre syndrome (GBS), including the subtypes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS) were examined for the presence of anti-ganglioside antibodies using the ganglioside agglutination assay, and the enzyme-linked immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies to gangliosides were detected in 21 (53%) of the GBS patients by agglutination assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with more than one ganglioside. Antibodies were not found in the control sera that were studied. The agglutination assay may be useful for rapid screening of GBS sera for antibodies to multiple gangliosides.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
ACUTE MOTOR NEUROPATHY
Guillain-Barre syndrome without sensory loss (acute motor neuropathy). A subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barre Study Group. Visser LH, Van der Meche FG, Van Doorn PA, Meulstee J, Jacobs BC, Oomes PG, Kleyweg RP, Meulstee J. Department of Neurology, University Hospital Dijkzigt, The Netherlands.	Brain 1995 Aug;118 ( Pt 4):841-7 Abstract quote We analysed data obtained from 27 out of a group of 147 patients with Guillain-Barre syndrome, who did not have sensory loss during a follow-up period of 6 months (motor Guillain-Barre syndrome). These patients had a distinctive clinical pattern compared with the other 120 Guillain-Barre syndrome patients. The clinical course was marked by a more rapid onset of weakness (3.9 versus 6.1 days, P = 0.002), an earlier nadir (6.3 versus 9.1 days, P < 0.001), an initially predominant distal weakness (67% versus 27%, P < 0.001), sparing of the cranial nerves (26% versus 68%, P < 0.001) and the disease was more often preceded by a gastro-intestinal illness (41% versus 13%, P = 0.001) often caused by a Campylobacter jejuni infection (67% versus 28% in the other Guillain-Barre syndrome patients, P < 0.001). High titres of anti-GM1 antibodies were also significantly more common in motor Guillain-Barre syndrome patients (42% versus 5%, P < 0.001). Electromyographic data of the motor Guillain-Barre syndrome patients at nadir revealed little or no evidence for demyelination. Abundant denervation activity was present in half of the patients. The response to immune globulin treatment was good but with plasma exchange significantly fewer motor Guillain-Barre syndrome patients reached the stage of independent locomotion after a follow-up period of 6 months especially if the acute motor neuropathy occurred after a C.jejuni infection.
ACUTE SMALL FIBRE SENSORY NEUROPATHY
Acute small fibre sensory neuropathy: another variant of Guillain-Barre syndrome? Seneviratne U, Gunasekera S. Department of Neurology, Ratnapura General Hospital, Ratnapura, Sri Lanka Institute of Neurology, National Hospital of Sri Lanka, Colombo 8, Sri Lanka.	J Neurol Neurosurg Psychiatry 2002 Apr;72(4):540-2 Abstract quote Six patients who presented with acute sensory neuropathy were studied. All patients underwent detailed clinical assessment along with electrophysiological tests and relevant laboratory investigations. All patients had acute onset numbness, reaching the peak deficit within 4 weeks. Four of them had associated burning dysaesthesia. An antecedent illness was reported in four; diarrhoea in three, and urinary tract infection in one. The neurological examination disclosed normal muscle strength, symmetric glove and stocking type sensory loss for pain and temperature, normal proprioception, and vibration senses with normal or brisk tendon reflexes. Analysis of CSF demonstrated albuminocytological dissociation in all. Routine motor and sensory nerve conduction studies were normal. Sympathetic skin responses were also normal except for the lower limbs in one patient. Stool cultures for Campylobacter jejuni were negative. The outcome was favourable. Burning dysaesthesia disappeared within 4 months. Numbness and objective sensory loss tended to persist longer. The clinical features and normal routine nerve conduction studies, which assess large diameter nerve fibre function, indicate small sensory fibre dysfunction in the group. Their presentation and CSF findings would fit into the diagnosis of sensory Guillain-Barre syndrome. The current study suggests that acute small fibre sensory neuropathy (ASFSN) is another clinical entity which could perhaps be included in the heterogeneous range of Guillain-Barre syndrome.
FULMINANT DISEASE
Fulminant Guillain-Barre syndrome mimicking cerebral death: case report and literature review. Vargas F, Hilbert G, Gruson D, Valentino R, Gbikpi-Benissan G, Cardinaud JP. Medical Intensive Care Unit B, Pellegrin Hospital, Bordeaux, France.	Intensive Care Med 2000 May;26(5):623-7 Abstract quote A 45-year-old woman was admitted to the intensive care unit (ICU) for respiratory arrest. One day prior to admission, she had been nauseated and in a state of total exhaustion. On the night of admission she was unresponsive and developed gasping respiration. The patient was comatose with absent brainstem reflexes and appeared brain dead. Blood chemistry findings and brain magnetic resonance imaging were normal. Electroencephalogram revealed an alpha rhythmical activity unresponsive to painful or visual stimuli. The cerebrospinal fluid showed an albuminocytological dissociation. Guillain-Barre syndrome (GBS) was suspected. The electrophysiological evaluation revealed an inexcitability of all nerves. The pathological findings of the sural nerve biopsy indicated an axonal degeneration secondary to severe demyelination. GBS can very rarely present with coma and absent brainstem reflexes. This case illustrates the importance of electrophysiological tests and laboratory and imaging studies in patients with suspected brain death where a cause is not clearly determined.
MILLER-FISHER SYNDROME
Miller fisher syndrome: a hospital-based retrospective study. Yuan CL, Wang YJ, Tsai CP. Neurology, The Neurological Institute, Veterans General Hospital, Taipei, Taiwan, ROC.	Eur Neurol 2000;44(2):79-85 Abstract quote Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and ophthalmoplegia, is generally considered as a variant of Guillain-Barre syndrome (GBS). However, some investigators believed that the syndrome could be explained by a central origin. To obtain more information about MFS for comparison with GBS, we conducted a retrospective study by analyzing the clinical data of MFS patients admitted to our hospital over a period of 11 years. The calibrated male/female ratio was 1.65. A seasonal clustering in winter was noted. The percentage of MFS among GBS was especially high (18%, 11/60) in Taiwan when compared with other series. Involvement of limb muscle strength, autonomic function and cranial nerves, except ocular motor nerves, was rarely found in our patients. When MFS is accompanied by limb weakness, it might represent a transitional form between MFS and GBS. Bulbar palsy and dysautonomia might predict a relatively poor prognosis. To obtain more reliable information, lumbar puncture should be done 1 week after disease onset, and electrophysiological tests should be done serially in every MFS patient. Eighty percent (80%, 4/5) of our patients were positive for IgG anti-GQ(1b) antibody activity. In our study, there is more evidence indicating that MFS is a peripheral nervous system disorder; however, no definite conclusion could be made as to whether MFS is exclusively a peripheral or central nervous system disorder. We think MFS is an immune-mediated clinical entity which mainly involves the peripheral nervous system with rare involvement of other parts of the central nervous system.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
PERIPHERAL NERVE
Physiologic-pathologic correlation in Guillain-Barre syndrome in children. Lu JL, Sheikh KA, Wu HS, Zhang J, Jiang ZF, Cornblath DR, McKhann GM, Asbury AK, Griffin JW, Ho TW. Department of Neurology, Beijing Children's Hospital, PRC.	Neurology 2000 Jan 11;54(1):33-9 Abstract quote OBJECTIVE: To correlate electrophysiologic patterns with sural nerve pathology in children with Guillain-Barre syndrome (GBS). BACKGROUND: Based on electrophysiologic and pathologic observations, GBS has been divided into demyelinating and axonal subtypes. The acute motor axonal neuropathy (AMAN) involves predominantly motor nerve fibers with a physiologic pattern suggesting axonal damage, whereas the acute inflammatory demyelinating polyneuropathy (AIDP) involves both motor and sensory nerve fibers with a physiologic pattern suggesting demyelination. In this study, we sought to confirm these observations by correlating sural nerve pathology with electrophysiologic findings in GBS patients. METHODS: Biopsies of sural nerve from 29 of 50 prospectively studied GBS patients were obtained. Nerves were examined by light and electron microscopy, and with immunocytochemistry for macrophages, lymphocytes, and complement activation products. RESULTS: Sural nerves from AMAN patients were normal or had only a few (0.1% to 0.7%) degenerating fibers without lymphocytic infiltration or complement activation. One patient with reduced sural sensory nerve action potential classified as acute motor sensory axonal neuropathy (AMSAN) had many degenerating fibers (2.3%) in the sural nerve. All three AIDP patients displayed active demyelination, and in two patients, lymphocytic infiltration and complement activation products were observed on the abaxonal Schwann cell surface. CONCLUSION: Classification of Guillain-Barre syndrome subtypes based on motor conduction studies correlates closely with pathologic changes seen in sural nerve. In acute motor axonal neuropathy cases, the sural nerve is almost completely spared pathologically. In acute inflammatory demyelinating polyneuropathy cases, macrophage-mediated demyelination and lymphocytic infiltration are common in the biopsies of sural nerves.
Guillain-Barre syndrome: clinical analysis and pathological study on sural nerve biopsy of forty cases. Guo Y, Wang C, Gao S, Ren H. Department of Neurology, Peking Union Medical College Hospital, Beijing, China.	Chin Med J (Engl) 1997 Sep;110(9):690-3 Abstract quote OBJECTIVE: To make clinical analysis and pathological study on 40-case Gullain-Barre syndrome with sural nerve biopsy. METHODS: A total of 90 cases of GBS were retrospectively analyzed of which sural nerve biopsies were performed in 40 cases. The type of GBS was determined according to Asbury and Ropper criteria, and its correlation with pathological findings was studied. RESULTS: In the 40 biopsy cases, demyelination was the predominant pathological change in 38 cases. Mild axonal degeneration was also seen in 13 of the 38 cases. Prominent axonal degeneration was seen in only 2 of 13 cases. The increased monocyte infiltration and varied capillary permeability were observed in 19 of 25 cases. Onion-bulb like changes were seen in 6 cases. CONCLUSION: We studied the correlation between paresthesia and the pathological findings of sural nerve biopsy and concluded that sural nerve biopsy is very useful in the diagnosis of GBS and its variant.
Severe axonal degeneration in acute Guillain-Barre syndrome: evidence of two different mechanisms? Feasby TE, Hahn AF, Brown WF, Bolton CF, Gilbert JJ, Koopman WJ. Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.	J Neurol Sci 1993 Jun;116(2):185-92 Abstract quote Four cases of severe acute Guillain-Barre syndrome (GBS) characterized by severe axonal degeneration are presented. All had electrically inexcitable motor nerves as early as 4 days after onset. The disease was rapid in onset and the residual disability was severe. Two different types of pathology were seen. Nerve biopsies in 3 cases showed severe axonal degeneration without inflammation or demyelination. Autopsy in one of these cases showed that the dorsal and ventral roots were also significantly affected. These cases illustrate the primary axonal form of GBS. Nerve biopsy in the fourth case at day 15 showed marked inflammation and demyelination with axonal degeneration. Contralateral nerve biopsy at day 75 showed almost complete loss of axons. This case illustrates another type of axonal degeneration, that which occurs secondary to inflammation and demyelination.
Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome. Hughes R, Atkinson P, Coates P, Hall S, Leibowitz S. Department of Neurology, United Medical School, Guy's Hospital, London, United Kingdom.	Muscle Nerve 1992 May;15(5):568-75 Abstract quote T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barre syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases. Cytomegalovirus (CMV) genome was not detected with the polymerase chain reaction.
Pathology of the Guillain-Barre syndrome. Prineas JW.	Ann Neurol 1981;9 Suppl:6-19 Abstract quote The Guillain-Barre syndrome is a distinctive neuropathy characterized pathologically by the presence of inflammatory lesions which occur scattered throughout the peripheral nervous system. The lesions consist of circumscribed areas in which myelin is lost in the presence of lymphocytes and macrophages. Myelin damage of effected largely by macrophages, which penetrate the basement membrane around nerve fibers and strip what appears to be normal myelin away from the body of the Schwann cell and off the axon. While there is evidence that this activity is immune mediated, the precise mechanism that leads macrophages to seek out and amputate a specialized region of the Schwann cell plasma membrane remains unexplained.

 

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS	Luxol Fast blue stain will show loss due to demyelinization
IMMUNOPEROXIDASE
ELECTRON MICROSCOPY
Ultrastructural study of peripheral nerve in Guillain-Barre syndrome presence of mononuclear cells in axons. Brechenmacher C, Vital C, Laurentjoye L, Castaing Y.	Acta Neuropathol Suppl (Berl) 1981;7:249-51 Abstract quote As has been shown during the course of experimental allergic neuritis, in the Guillain-Barre syndrome there is an invasion of the myelin sheath in certain fibres by a mononuclear cell, with an intact axon. In a series of 45 cases we have been able to show this feature in 31 cases. In certain cases the cytoplasm prolongation of the invading cell was seen in the myelin sheath, forcing apart two neighbouring layers. In five cases we have furthermore observed the presence of mononuclear cells located either between the myelin and the axon which is deformed, or on the inside of the axon. Such an anomaly was frequent in one recent case and was occasionally found in four other cases.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
ALCOHOL POLYNEUROPATHY
Alcohol-related acute axonal polyneuropathy: a differential diagnosis of Guillain-Barre syndrome. Wohrle JC, Spengos K, Steinke W, Goebel HH, Hennerici M. Department of Neurology, Klinikum Mannheim of the University of Heidelberg, Germany.	Arch Neurol 1998 Oct;55(10):1329-34 Abstract quote BACKGROUND: Chronic axonal polyneuropathy is a well-known clinical sequela of excessive alcohol consumption; however, acute axonal polyneuropathy related to alcohol abuse is less well recognized. OBJECTIVE: To describe alcohol-related acute axonal polyneuropathy in 5 chronic alcoholics who developed ascending flaccid tetraparesis and areflexia within 14 days. METHODS: Case series with clinical, laboratory, electrophysiological, and, in 1 patient, biopsy data. RESULTS: All 5 patients consumed a daily average of 250 g of alcohol, and 4 had lost a substantial amount of weight recently. Additional clinical features included painful paresthesia, myalgia, and glove and stocking-type sensory loss. Repeated cerebrospinal fluid examinations failed to show the marked increase of protein concentration with normal cell count typical of Guillain-Barre syndrome, although the protein level was mildly elevated in 1 patient. Blood laboratory findings were consistent with longstanding alcohol abuse. Compound muscle and sensory nerve action potentials were absent or reduced, while conduction velocities were normal or mildly reduced. Three to 4 weeks after onset, needle electromyography displayed moderate to severe fibrillations and positive sharp waves in addition to normal motor unit potentials, indicating an acute axonal polyneuropathy; this was confirmed by sural nerve biopsy in 1 patient. CONCLUSIONS: Excluding other factors, we assume that in these patients the combination of alcohol abuse and malnutrition caused severe acute axonal polyneuropathy. Its distinction from Guillain-Barre syndrome is important because treatment requires balanced diet, vitamin supplementation, and abstinence from alcohol, while immunotherapy may not be indicated.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Prognostic factors of Guillain-Barre syndrome after intravenous immunoglobulin or plasma exchange. Dutch Guillain-Barre Study Group. Visser LH, Schmitz PI, Meulstee J, van Doorn PA, van der Meche FG. Department of Neurology, University Hospital Dijkzigt/Dr. Daniel den Hoed Cancer Center and Erasmus University, Rotterdam, The Netherlands.	Neurology 1999 Aug 11;53(3):598-604 Abstract quote OBJECTIVE: To determine the influence of clinical, laboratory, and electrodiagnostic factors on the prognosis of Guillain-Barre syndrome (GBS). BACKGROUND: Identification of prognostic factors may lead to better selection of patients with a poor prognosis for new therapeutic trials. METHODS: The authors studied 147 patients with GBS who participated in the Dutch GBS trial comparing the effect of IV immunoglobulins with plasma exchange (PE). Outcome was measured at 8 weeks because half of the patients had recovered independent locomotion by then and at 6 months, the endpoint of the study. RESULTS: Multivariate logistic regression revealed the following factors predicting outcome (inability to walk independently) at 8 weeks: a preceding gastrointestinal illness (yes, no), age (> or =50, <50 years), Medical Research Council sum score (<40, > or =40) at the start of treatment, and-described for the first time-a recent cytomegalovirus (CMV) infection (yes, no). At 6 months, the same clinical factors were found, but an initial rapid progression of weakness also appeared to be a prognostic factor. Analysis of treatment interactions revealed that the effect of diarrhea was more pronounced in the PE-treated group. CONCLUSIONS: The main predictors of outcome in GBS are clinical factors. Diarrhea is an important poor predictor of outcome, especially for the PE-treated group, and a recent CMV infection predicts delayed early recovery.
The prognosis and main prognostic indicators of Guillain-Barre syndrome. A multicentre prospective study of 297 patients. The Italian Guillain-Barre Study Group.	Brain 1996 Dec;119 ( Pt 6):2053-61 Abstract quote To assess the prognosis of the Guillain-Barre syndrome and identify the main prognostic indicators, 297 patients with Guillain-Barre syndrome recruited through a network of Italian centres were followed up for 24 months or until clinical recovery, whichever was earliest. For each patient the time to plateau, improvement, clinical recovery, or death was calculated, and prognostic indicators (age, sex, antecedent events, disability at admission and nadir, electrophysiological patterns) and treatments were noted. The mean duration of follow-up was 309 days. During this period, 212 patients (71%) recovered, 48 (16%) had residua and 33 (11%) died. The mean times to nadir, improvement and clinical recovery were 12, 28 and 200 days. Using life-tables and survival curves, the cumulative probability of achieving the plateau of symptoms was 73% by 1 week and 98% by 4 weeks. Improvement started during the first week in 36% of cases and within 4 weeks in 85%. The rates of clinical recovery at 1 and 4 weeks, 6, 12 and 24 months were 4, 24, 57, 70 and 82%, respectively. The chance of recovery was significantly affected by age, antecedent gastroenteritis, disability, electrophysiological signs of axonopathy, latency to nadir and duration of active disease. The main treatments did not seem to affect the chance of recovery.
RECURRENCE
Recurrent Guillain Barre' Syndrome: a clinical, electrophysiological and morphological study. Taly AB, Gupta SK, Anisya V, Shankar SK, Rao S, Das KB, Nagaraja D, Swamy HS.	J Assoc Physicians India 1995 Apr;43(4):249-52 Abstract quote Of the 220 patients of acute idiopathic demyelinating polyneuritis (AIDP/GBS) seen over a seven year period, 15 patients (M:F:11:4) had a relapsing course (6.8%). Their ages ranged from 8 yrs to 70 yrs. They had 36 episodes at a variable interval of 3 months to 25 yrs. Relapse rate varied from one to four. Antecedent events were noted during 16 episodes in 9 patients but the triggering factors were varied. Clinical features of individual episodes were similar to the acute monophasic illness, although they differed inseverity from one episode to the other. Autonomic disturbances were rare. Albuminocytological dissociation was observed during 19 of the 24 episodes. Electrophysiological abnormalities were observed during 19 of the 24 episodes. Electrophysiological abnormalities were present in all and were comparable with patients of non-recurrent illness. Sural nerve biopsy in 3 patients showed evidence of demyelination, remyelination, Wallerian degeneration and myelin breakdown but none had features of inflammation. With the exception of one death, functional recovery was complete in the majority of patients, irrespective of the type of therapeutic intervention. Acute onset, frequent facial involvement, brief clinical course, near complete recovery and very long asymptomatic periods may distinguish these patients of acute relapsing demyelinating polyneuropathy (ARDP) from chronic relapsing demyelinating polyneuropathy. Relapses in GBS are however unpredictable and recurrent GBS is indistinguishable clinically, electrophysiologically and morphologically from the more frequently seen non-recurrent form of monophasic GB Syndrome. A biochemical or immunological marker may help in this distinction.
Recurrent Guillain-Barre syndrome. Clinical and laboratory features. Grand'Maison F, Feasby TE, Hahn AF, Koopman WJ. Department of Clinical Neurological Sciences, Victoria Hospital, University of Western Ontario, London, Canada.	Brain 1992 Aug;115 ( Pt 4):1093-106 Abstract quote The clinical and laboratory features of recurrent Guillain-Barre syndrome (RGBS) were reviewed in 12 patients in whom a total of 32 episodes fulfilled accepted criteria for Guillain-Barre syndrome (GBS). All patients were asymptomatic or only mildly symptomatic between attacks. In a given patient, the time to reach peak deficit from the onset of symptoms, the functional grade at peak deficit and the duration of the intervals between episodes varied considerably and unpredictably from one episode to the next. Analysis of these parameters across the entire group revealed no significant change as the number of attacks increased. The distribution of weakness varied between episodes with the possible exception of features of the Miller Fisher variant which were more constant. Tremor was noted in two patients and enlarged nerves in one patient. There was no evident response to immunosuppressive therapy. Results of cerebrospinal fluid (CSF) analysis and nerve conduction studies during recurrences were those expected in typical monophasic GBS. On nerve biopsy, onion bulb formations were sometimes observed after several recurrences. The following characteristics of RGBS may be sufficiently distinctive from those of chronic relapsing polyneuropathy to justify their nosological separation: rapid onset of symptoms with subsequent complete or near complete recovery, high incidence of an antecedent illness, lack of an apparent response to immunosuppressive therapy and normal CSF protein levels at the onset of a recurrence.
Acute relapsing Guillain-Barre syndrome after long asymptomatic intervals. Wijdicks EF, Ropper AH. Neurological/Neurosurgical Intensive Care Unit, Massachusetts General Hospital, Boston 02114.	Arch Neurol 1990 Jan;47(1):82-4 Abstract quote Five patients who recovered from an initial episode of Guillain-Barre syndrome had acute relapses 4, 10, 15, 17, and 36 years later, respectively. Two patients had multiple subsequent relapses. The antecedent illnesses, distribution of weakness, and clinical courses of each relapse were similar for each patient, except that relapses in three patients were briefer than the initial episode. One patient had asymptomatic sarcoidosis. Pharyngeal, oculomotor, and diaphragmatic weakness requiring a ventilator were common. Complete recovery or mild residual deficits, return of reflexes, normal cerebrospinal fluid protein at the onset of recurrent episodes, and normal or virtually normal nerve conduction velocities at various times distinguished these patients from those with more typical chronic relapsing inflammatory polyneuropathy.
TREATMENT
COMBINED MODALITY
Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barre syndrome. Plasma Exchange/Sandoglobulin Guillain-Barre Syndrome Trial Group.	Lancet 1997 Jan 25;349(9047):225-30 Abstract quote BACKGROUND: The relative efficacy of plasma exchange (PE) and intravenous immunoglobulin (IVIg) for the treatment of Guillain-Barre syndrome has not been established. We compared PE with IVIg, and with a combined regimen of PE followed by IVIg, in an international, multicentre, randomised trial of 383 adult patients with Guillain-Barre syndrome. METHODS: The patients were randomly assigned PE (five 50 mL/kg exchanges over 8-13 days), IVIg (Sandoglobulin, 0.4 g/kg daily for 5 days), or the PE course immediately followed by the IVIg course. The inclusion criteria were severe disease (aid needed for walking) and onset of neuropathic symptoms within the previous 14 days. Patients were followed up for 48 weeks. FINDINGS: Four patients were excluded because they did not meet the randomisation criteria. All the remaining 379 patients were assessed for the major outcome criterion-change on a seven-point disability grade scale-by an observer unaware of treatment assignment, 4 weeks after randomisation. At that time, the mean improvement was 0.9 (SD 1.3) in the 121 PE-group patients, 0.8 (1.3) in the 130 IVIg-group patients, and 1.1 (1.4) in the 128 patients who received both treatments (intention-to-treat analysis). None of the differences between the groups for this major outcome criterion was significant. The difference between PE alone and IVIg alone was so small that a 0.5 grade difference was excluded at the 95% level of confidence. There was no significant difference between any of the treatment groups in the secondary outcome measures: time to recovery of unaided walking, time to discontinuation of ventilation, and trend describing the recovery from disability up to 48 weeks. There was a non-significant trend towards a more favourable outcome on some outcome measures with combined treatment. INTERPRETATION: In treatment of severe Guillain-Barre syndrome during the first 2 weeks after onset of neuropathic symptoms, PE and IVIg had equivalent efficacy. The combination of PE with IVIg did not confer a significant advantage.
Treatment of Guillain-Barre syndrome with high-dose immune globulins combined with methylprednisolone: a pilot study. The Dutch Guillain-Barre Study Group.	Ann Neurol 1994 Jun;35(6):749-52 Abstract quote In an open study 25 patients with Guillain-Barre syndrome were treated for 5 days with intravenous immune globulins in a dose of 0.4 gm/kg of body weight/day and 0.5 gm of methylprednisolone intravenously per day. The results of this combined treatment were compared with the results from a group of 74 patients who were treated with immune globulins only in a recent Dutch Guillain-Barre trial. In the methylprednisolone-immune globulin treatment group, 19 of 25 patients (76%) improved by one or more functional grades after 4 weeks, as compared with 39 (53%) of 74 patients treated with immune globulin alone (p = 0.04). Also the median time required to the stage of walking independently was reduced in the methylprednisolone-immune globulin treatment group. This pilot study suggests that combined treatment with methylprednisolone and immune globulins in patients with the Guillain-Barre syndrome is more effective than treatment with immune globulins alone; a randomized clinical trial might confirm this.
GABAPENTIN
Gabapentin for the treatment of pain in guillain-barre syndrome: a double-blinded, placebo-controlled, crossover study. Pandey CK, Bose N, Garg G, Singh N, Baronia A, Agarwal A, Singh PK, Singh U. Departments of Anaesthesiology and Critical Care Medicine and Bio-statistics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.	Anesth Analg 2002 Dec;95(6):1719-23 Abstract quote Pain syndromes of Guillain-Barre are neuropathic as well as nociceptive in origin. We aimed to evaluate the therapeutic efficacy of gabapentin in relieving the bimodal nature of pain in Guillain-Barre syndrome in a randomized, double-blinded, placebo-controlled, crossover study in 18 patients admitted to the intensive care unit for ventilatory support. Patients were assigned to receive either gabapentin (15 mg. kg(-1). d(-1) in 3 divided doses) or matching placebo as initial medication for 7 days. After a 2-day washout period, those who previously received gabapentin received placebo, and those previously receiving placebo received gabapentin as in the initial phase. Fentanyl 2 micro g/kg was used as a rescue analgesic on patient demand or when the pain score was >5 on a numeric rating scale of 0-10. The numeric rating score, sedation score, consumption of fentanyl, and adverse effects were noted, and these observed variables were compared. The numeric pain score decreased from 7.22 +/- 0.83 to 2.33 +/- 1.67 on the second day after initiation of gabapentin therapy and remained low during the period of gabapentin therapy (2.06 +/- 0.63) (P < 0.001). There was a significant decrease in the need for fentanyl from Day 1 to Day 7 during the gabapentin therapy period (211.11 +/- 21.39 to 65.53 +/- 16.17 [ micro g]) in comparison to the placebo therapy period (319.44 +/- 25.08 to 316.67 +/- 24.25 [ micro g]) (P < 0.001). IMPLICATIONS: Gabapentin, an antiepileptic drug, has been used effectively for different types of pain management. This study demonstrates that gabapentin has minimal side effects and is an alternative to opioids and nonsteroidal antiinflammatory drugs for management of the bimodal nature of pain of Guillain-Barre Syndrome patients.
Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Serpell MG. University Department of Anaesthesia and Pain Management, Gartnavel General Hospital, 30 Shelly Court, G12 0YN, Scotland, Glasgow, UK	Pain 2002 Oct;99(3):557-66 Abstract quote A double-blind, randomised, placebo-controlled 8-week study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain, using doses up to 2400mg/day. The study used a novel design that was symptom- rather than syndrome-based; an approach that aimed to reflect the realities of clinical practice. Participants had a wide range of neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. Patients were randomised to gabapentin (n=153) or placebo (n=152). Gabapentin was given in three divided doses, initially titrated to 900mg/day over 3 days, followed by two further increases, to a maximum of 2400mg/day if required by the end of week 5. The primary outcome measure was changed in average daily pain diary score (baseline versus final week). Over the 8 week study, this score decreased (i.e. improved) by 1.5 (21%) in gabapentin treated patients and by 1.0 (14%) in placebo treated patients (P=0.048, rank-based analysis of covariance). Significant differences were shown in favour of gabapentin (P<0.05) for the Clinician and Patient Global Impression of Change, and some domains of the Short Form-McGill Pain Questionnaire. Improvements were also shown in patient-reported outcomes in quality of life, as seen by significant differences in favour of gabapentin in several domains of the Short-Form-36 Health Survey. Gabapentin was well tolerated and the majority of patients completed the study (79 versus 73% for placebo). The most common adverse events were mild to moderate dizziness and somnolence, most of which were transient and occurred during the titration phase. This study shows that gabapentin reduces pain and improves some quality-of-life measures in patients with a wide range of neuropathic pain syndromes.
INTRAVENOUS IMMUNOGLOBULIN
A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barre syndrome. Dutch Guillain-Barre Study Group. van der Meche FG, Schmitz PI. Department of Neurology, Academic Hospital Rotterdam, The Netherlands.	N Engl J Med 1992 Apr 23;326(17):1123-9 Abstract quote BACKGROUND. The subacute demyelinating polyneuropathy known as Guillain-Barre syndrome improves more rapidly with plasma exchange than with supportive care alone. We conducted a multicenter trial to determine whether intravenous immune globulin is as effective as the more complicated treatment with plasma exchange. METHODS. To enter the study, patients had to have had Guillain-Barre syndrome for less than two weeks and had to be unable to walk independently. They were randomly assigned to receive either five plasma exchanges (each of 200 to 250 ml per kilogram of body weight) or five doses of a preparation of intravenous immune globulin (0.4 g per kilogram per day). The predefined outcome measure was improvement at four weeks by at least one grade on a seven-point scale of motor function. RESULTS. After 150 patients had been treated, strength had improved by one grade or more in 34 percent of those treated with plasma exchange, as compared with 53 percent of those treated with immune globulin (difference, 19 percent; 95 percent confidence interval, 3 percent to 34 percent; P = 0.024). The median time to improvement by one grade was 41 days with plasma exchange and 27 days with immune globulin therapy (P = 0.05). The immune globulin group had significantly fewer complications and less need for artificial ventilation. CONCLUSIONS. In the acute Guillain-Barre syndrome, treatment with intravenous immune globulin is at least as effective as plasma exchange and may be superior.

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