Skip Navigation

Guillain-Barré Syndrome and Influenza Virus Infection

  1. Valérie Sivadon-Tardy1,2,
  2. David Orlikowski2,3,
  3. Raphaël Porcher5,6,
  4. Tarek Sharshar2,3,
  5. Marie-Christine Durand2,4,
  6. Vincent Enouf7,8,
  7. Flore Rozenberg9,10,
  8. Christiane Caudie11,
  9. Djillali Annane2,3,
  10. Sylvie van der Werf7,8,
  11. Pierre Lebon8,9,
  12. Jean-Claude Raphaël2,3,
  13. Jean-Louis Gaillard1,2, and
  14. Elyanne Gault1,2,7,8
  1. 1Laboratoire de Microbiologie, Hôpital Ambroise Paré, Assistance Publique—Hôpitaux de Paris (AP-HP), Boulogne-Billancourt
  2. 2Université de Versailles—St. Quentin, Faculté de Médecine Paris-Ile-de-France-Ouest, Garches
  3. 3Service de Réanimation, Garches
  4. 4Physiologie et Explorations Fonctionnelles, Hôpital Raymond Poincaré (AP-HP), Garches
  5. 5Département de Biostatistique et Informatique Médicale, Hôpital St.-Louis (AP-HP), Paris
  6. 6Université, Paris
  7. 7Inserm U717, Paris
  8. 8Unité de Génétique Moléculaire des Virus Respiratoires, URA CNRS 3015, EA302 Université Paris 7, Paris
  9. 9Centre National de Référence du Virus Influenza (Région Nord), Institut Pasteur, Paris
  10. 10Laboratoire de Virologie, Hôpital Cochin—St. Vincent-de-Paul (AP-HP), Paris
  11. 11Université Paris Descartes, Faculté de Médecine, Paris
  12. 12Fédération de Biologie, Service d'Immunologie, Hôpital Neurologique, Lyon, France
  1. Reprints or correspondence: Dr. Elyanne Gault, Laboratoire de Microbiologie, Hôpital Ambroise Paré, 9, ave. Charles de Gaulle, 92100 Boulogne-Billancourt, France (elyanne.gault{at}apr.aphp.fr)
 
Next Section

Abstract

Background. In Western countries, the cause of 60% of all Guillain-Barré syndrome (GBS) cases remains unidentified. The number of cases of unidentified cause peaks in winter, and these cases are commonly preceded by respiratory tract infection or influenza-like illness. We investigated the triggering role of influenza virus infection.

Methods. Of 405 patients with GBS who were admitted to a French reference center during 1996–2004, 234 had cases caused by an unidentified agent. We used time-series methods to study the correlation between the monthly incidence of such cases and influenza-like illnesses reported by the Sentinelles surveillance network. We analyzed anti-influenza antibodies using complement fixation testing and hemagglutination-inhibition assays. We studied etiological subgroups using Wilcoxon and Fisher's exact tests.

Results. We found a positive association between the monthly incidence of GBS caused by an unidentified agent and reported influenza-like illnesses. Of 73 patients whose cases occurred during periods in which there was a possible link to influenza, 10 (13.7%) had serological evidence of recent influenza A, and 4 (5.5%) had serological evidence of influenza B. Eight of 10 influenza A—related cases occurred during “major” influenza seasons, and antibodies specific to the current epidemic strain were found in 9 cases. Most patients with influenza A—related cases were aged <65 years, and none had antiganglioside antibodies. Influenza-related cases differed both from Campylobacter jejuni—related cases, with regard to the lack of need for mechanical ventilation (P=.014), and from the cases caused by an unidentified agent, with regard to the presence of preceding influenza-like illness or respiratory tract infection (P=.015) and longer time from the infectious event to GBS onset (P=.04).

Conclusions. Influenza viruses are infrequent triggering agents of GBS but may play a significant role during major influenza outbreaks. Influenza-related GBS displays specific features and is not associated with antiganglioside antibody response, which suggests the presence of underlying immune mechanisms.

Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in poliomyelitis-free regions [1]; the estimated incidence of GBS is 0.4–4.0 cases per 100,000 population per year [2]. Most cases are thought to result from an aberrant immune response triggered by a recent infectious disease or vaccination. GBS occurs after acute infectious disease (usually respiratory tract infection [RTI] or gastrointestinal illness [GI]) in 60%–70% of patients [3]. Campylobacter jejuni and cytomegalovirus are the most commonly identified infectious causes in Western countries, accounting for 13%–39% and 10%–15% of GBS cases, respectively [1, 4, 5]. Other possible infectious causes include Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae [1, 4, 5]. Vaccinations have also been implicated in GBS; an example is the influenza vaccine used during the mass vaccination campaign against swine influenza in the United States from 1976 through 1977 [6]. However, 60%–70% of GBS cases in Western countries remain without any identified cause.

We recently reported that, in the greater Paris area, GBS caused by an unidentified agent (i.e., not related to the aforementioned agents) occurred more frequently during the winter season and was commonly preceded by RTI or influenza-like syndrome (ILS) [5]. These results were recently supported by Tam et al. [7], who demonstrated a significant association between the weekly number of GBS-related hospitalizations in England and the weekly number of laboratory reports of influenza cases. However, the cases in those studies were not virologically documented, and no information was provided about either the characteristics of the cases that were possibly linked to influenza or the virus types involved.

Here, we demonstrate a direct link between GBS and recent influenza virus infection. However, we show that influenza-related cases are uncommon and, in France, are mainly observed during major outbreaks of influenza. We also show that influenza-related cases constitute a distinctive entity and that they are not associated with the generation of antiganglioside antibodies; these findings suggest that a specific pathological mechanism may be involved in influenza-related GBS.

Previous SectionNext Section

Patients and Methods

Background information. The medical intensive care unit at the Raymond Poincaré Hospital (Garches, France) is a regional reference center for the management of adult patients with GBS. All patients with GBS who are admitted to the hospital are asked to participate in current therapeutic protocols. Participating patients are observed prospectively for 12 months, as described elsewhere [5, 8–11]. Clinical data collection, serum antibody detection, and electrophysiological testing are part of current treatment of patients admitted to our health care center to treat GBS. Study of anti-influenza antibodies was performed using a declared serum collection, according to the French legislation. No further ethical approval was required for this study.

Study population. Four-hundred five patients with clinically defined GBS (according to the criteria of Asbury and Cornblath [12]), were admitted consecutively during 1996–2004. At hospital admission, pretreatment serum samples were obtained and clinical data were collected—namely on infectious events (GI, RTI, ILS, and other), vaccinations within the 2 previous months, and time from the onset of the infectious event to the onset of neurological signs [5, 11]. Serum antibody titers against C. jejuni, M. pneumoniae, cytomegalovirus, and Epstein-Barr virus were determined, as described elsewhere [5]. Antigangliosides IgM and IgG were detected by immunodot blot and enzymatic immunoassay (GanglioCombi; Bühlmann Laboratories) [13]. Electrophysiological testing was performed using a Neuropack SIGMA EMG device (MESA Nihon Kohden), as described elsewhere [9].

Data from surveillance networks. We used data provided by 2 independent surveillance networks: Sentinelles and Groupes Régionaux d'Observation de la Grippe (Regional Influenza Surveillance Group). Sentinelles is a national network that collects clinical reports of illnesses, such as influenza-like illness (ILI; defined as sudden fever [temperature, >39°C], myalgia, and respiratory signs) and acute GI, from general practitioners. The number of cases is reported weekly at the Sentinelles Web site [14]. Groupes Régionaux d'Observation de la Grippe is an influenza-monitoring network; it collects clinical reports of acute RTI from general practitioners and pediatricians and virological data from the same community. Data on past and current epidemics are available at the Groupes Régionaux d'Observation de la Grippe Web site [15].

Time-series methods. The analysis of the relationship between the incidence of GBS caused by an unknown agent and the incidence of ILI or GI was performed using the time-series methods, after some seasonal adjustment to avoid the detection of spurious associations that reflect only a similar seasonality [16]. As described elsewhere [17], we tested the link between the patterns of GBS and ILI cases that were not explained by usual seasonal variation, which is more easily interpreted in terms of a possible direct influence of ILI on GBS. This interpretation can be strengthened by evidence of the unidirectionality of the association of one series toward the other, which is tested by lagged correlation or regression. First, the expected seasonal variations in the numbers of cases of GBS(t) (i.e., the number of cases of GBS caused by an unknown agent that were observed during month t) and ILI(t) (i.e., the number of cases of ILI during month t) were estimated using usual periodic modeling of time series. Because the number of cases of GBS was low, all data were analyzed on a monthly rather than weekly periodicity; a Poisson model was used for GBS(t), as proposed by Jones et al. [18]. This model supposes that GBS(t) is a Poisson variable of mean µ(t), with Because we have already revealed a yearly seasonality with regard to the number of cases of GBS caused by unknown agents [5], no higher-order harmonics were added to this model. We subsequently defined the residual variation in the number of GBS cases by the difference between the numbers of observed and expected cases, as follows: A similar methodology was used for ILI(t), but higher numbers of cases allowed a direct periodic model, as follows: Rf t is the residual variation in the number of ILI cases. After Rgb t and Rf t were obtained, cross-correlation plots of both series at different time lags were computed to detect association between both series. As proposed by Hubert et al. [17], lagged regression with autocorrelated errors was also used, with the model The hypothesis tested is the existence of an association between residual variation in the number of GBS cases during month t and residual variation in the number of cases of ILI during month (t-k). Lags k were between −6 and 6; negative lags allowed verification if the association was directional. To show a potential causal relationship between ILI and GBS, we would expect that some of the backward-lagged (k>0) regression coefficients or cross-correlation coefficients would be statistically significant and that none of the forward-lagged (k<0) coefficients would be statistically significant. Because of high serial correlation, the models for each value of k were fit separately, and an autoregressive structure for the residual errors e t was allowed in the model. Similar methodology was used for analysis of GBS and GI cases.

Other statistical methods. Characteristics of patient subgroups were compared using the Fisher's exact test and the Wilcoxon rank-sum test. To account for multiplicity, P values were adjusted by Hochberg's method [19]. All tests were 2 tailed, and statistical significance was set at P=.05; analyses were performed using R software, version 2.4.0 (The R Foundation for Statistical Computing).

Influenza serology. Antibodies to influenza A and B were assayed by complement fixation tests (CFT; Virion/Serion), and recent infection was defined by titers ⩾64. Anti—influenza A antibodies directed against vaccine and circulating strains were measured by hemagglutination-inhibition (HAI) assays, as described elsewhere [20]. Corresponding postinfectious ferret serum samples were tested as control samples. Serum samples were independently tested against 4 hemagglutinin units of each virus, and HAI assays were performed with 0.5% guinea pig erythrocytes. Nonspecific erythrocyte agglutination was ruled out by mock HAI.

Previous SectionNext Section

Results

The occurrence of cases of GBS caused by unidentified agents correlates with peaks in the incidence of ILI. Of the 405 patients, 171 patients (42%) had serological evidence of recent infection due to a known causative agent (103 patients had infection due to C. jejuni, 56 had infection due to cytomegalovirus, 10 had infection due to M. pneumoniae, and 4 had infection due to Epstein-Barr virus), and 234 patients (58%) had GBS caused by an unidentified agent (figure 1). The dates of GBS onset in the 234 patients with GBS caused by an unidentified agent were compared with the monthly incidence of both acute ILI and GI (provided by the Sentinelles network). Cross-correlation plots and lagged regression with auto-correlated errors—combining series of cases of ILI and cases of GBS caused by an unidentified agent—revealed a positive association between the 2 disorders, with a significantly elevated ILI incidence both 1 and 2 months before GBS onset ( P=.004 and P=.044, respectively) (figure 2). No statistically significant associations were found for backward lag times (i.e., no correlation was found for GBS caused by an unidentified agent before the occurrence of ILI). This directionality of the association supports a causal link between GBS caused by an unidentified agent and ILI. The specificity of this link was also supported by the lack of any statistically significant association between GBS caused by an unidentified agent and reported cases of GI or between GBS caused by an identified agent and reported cases of ILI (data not shown).

Figure 1
View larger version:
Figure 1

Flow of cases through the study. aOne hundred three cases (60%) due to Campylobacter jejuni, 56 (32%) due to cytomegalovirus, 10 (6%) due to Mycobacterium pneumoniae, and 4 (2%) due to Epstein Barr virus. bBy cross-correlation plots and lagged regression with autocorrelated errors. cBy complement fixation testing. dNine of 10 patients presented with significant hemagglutination-inhibition titers against the current epidemic strain. GBS, Guillain-Barré syndrome; ILI, influenza-like illness.

Figure 2
View larger version:
Figure 2

A, Monthly incidence of influenza-like illness (ILI; solid line) and Guillain-Barré syndrome (GBS; dashed line) caused by an unidentified agent. B, t Ratios of lagged-regression coefficients between residual cases of GBS caused by an unidentified agent at month t and ILI at month t−, for lags of −3 to 3. Horizontal dashed lines indicate 5% significance level of a 2-sided test of association.

Influenza-related cases of GBS mainly occur during major influenza seasons and involve current epidemic strains. Among the study population, 73 patients were selected because their neurological defects had started during periods of positive association with epidemic ILI (during the 2 months after and the 2 weeks before peaks in the number of cases of ILI, to reduce the risk of omitting cases) (table 1) [21, 22].

The 10 cases of GBS in patients with serological evidence of recent influenza A were not evenly distributed from 1996 through 2004 (figure 3). Eight cases occurred during 2 seasons that were considered to be “major” in terms of influenza activity: 1996–1997 (4 cases) and 1999–2000 (4 cases) [23]. In addition, season 1996–1997 was characterized by the circulation of the A/Nanchang/933/95(H3N2) virus, which accounted for an unusually high morbidity rate. The 2 remaining cases occurred during “moderate” seasons (1997–1998 and 1998–1999), and no case was detected from 2000 through 2004, when influenza activity was “mild” [23].

Figure 3
View larger version:
Figure 3

Distribution of the 73 Guillain-Barré syndrome (GBS) cases that occurred during epidemic seasons 1996–2004 by incidence of influenza-like illness and involved influenza strains in the greater Paris area. Weekly incidence of influenza-like illness, as provided by the Sentinelles surveillance network, is represented by black lines. Gray areas indicate periods of influenza virus circulation at epidemic rates, as provided by the National Influenza Centre (northern France). The circulating strains and their respective prevalence are indicated for each season. Boxes indicate the number of GBS cases during each studied season. Black boxes indicate cases related to influenza A, dashed boxes indicate cases related to influenza B, and white boxes indicate cases unrelated to influenza. Bay95, A/Bayern/7/95(H1N1); Bei93, B/Beijing/184/93; HK02, B/HongKong/1343/02; Nan95, A/Nanshang/933/95(H3N2); NC99, A/NewCaledonia/20/99(H1N1); Mos99, A/Moscow/10/99(H3N2); Pan99, A/Panama/2007/99(H3N2); Par99, B/Paris/1264/99 (antigenically related to BEI93); Sic99, B/Sichuan/379/99; Syd97, A/Sydney/5/97(H3N2); Wyo03, A/Wyoming/3/03(H3N2); Yam98, B/Yamanashi/166/98.

For each influenza A—related case, we used HAI to study the specific reactivity of influenza A antibodies against each viral strain circulating from 1995 (1 year before the study period) through 2000 and against the corresponding vaccine strains (figure 4). All patients but 1 (no specific HAI activity against tested strains) presented with significant HAI titers against the epidemic strain from the season of their GBS onset. One patient, who had been vaccinated 15 days before the onset of neurological symptoms, presented with high titers of reactivity (<1280) against both vaccine and circulating strains. These results suggested that the patient might have developed influenza shortly after (and despite) vaccination and then developed influenza-related GBS.

Figure 4
View larger version:
Figure 4

Hemagglutination-inhibition (HAI) reactivity against epidemic and influenza A vaccine strains for each influenza A—related case. Serum samples were tested against each prevalent strain from the period 1995–2004, as well as against vaccine strains when they were different from the epidemic strain. Reference serum samples from ferrets infected by each tested strain were included as control samples. Nonspecific erythrocyte agglutination was ruled out by mock infection. Strain A/Johanesburg/33/94(H3N2) (JHB94) was prevalent in 1995, one year before the study period; A/Singapore/6/86(H1N1) (SIN86) was included in the 1996–1997 and 1998–1999 vaccines, and A/Beijing/262/95(H1N1) (BEI95) was included in the 1999–2000 vaccines. Gray areas delimit relevant epidemic or vaccine strains for each considered season. Except for patient A5, high HAI titers were observed against the most prevalent strain for each season (boldface type). Note that this also applies to patient A3, who received influenza vaccine 15 days before developing neurological signs. Patient A6 presented with a serological profile suggestive of recent infection due to A/Sydney/5/97(H3N2) (SYD97) and with reactivity to JHB94 and A/Nanshang/933/95(H3N2) (NAN95), probably reflective of past infection or vaccination. Patient A10's profile suggests either a mixed infection due to A/NewCaledonia/20/99(H1N1) (NC99) and SYD97 (or A/Moscow/10/99(H3N2) [MOS99]) or a single current infection due to NC99; antibodies to SYD97 and MOS99 (H3N2 strains) reflected past infection or vaccination. *Cross-reactivity between strains A/Bayern/7/95(H1N1) (BAY95) and BEI95. **Cross-reactivity between strains SYD97 and MOS99, as evidenced after testing of serum samples from infected ferrets (results not shown).

Characteristics of GBS associated with recent influenza virus infection. The 14 patients with serological evidence of recent influenza virus infection comprised 8 male and 6 female patients (table 1). Nine of the 14 patients were aged <60 years, and 12 had ILS or RTI before GBS onset (time from ILS or RTI to GBS onset, 3–30 days). Only 1 patient had been vaccinated against influenza (15 days before GBS onset) (table 1). Thirteen patients presented with both sensory and motor defects. One patient developed bulbar dysfunction, and 5 developed facial palsy. Electrophysiological testing was performed for 9 patients, and testing revealed either demyelinating (4 patients) or equivocal (3 patients) profiles for most patients. None of the 14 patients had detectable antiganglioside antibodies. Seven patients were treated with plasma exchange, and the other 7 were treated with intravenous IgG. Only 2 patients, both with influenza B infection, received mechanical ventilation. One patient, with influenza A—related GBS, died, and 4 of 10 patients with available data had sequelae at a 1 year follow-up examination.

Table 1
View larger version:
Table 1

Characteristics of patients with Guillain-Barré syndrome (GBS) associated with recent influenza virus infection.

Influenza A—related GBS cases were compared with C. jejuni—related cases and with GBS cases due to an unidentified agent for which influenza CFT results were negative (table 2). Because of the small number of cases, the influenza B subgroup was not included in the analysis. Patients with influenza A—related GBS were less likely to receive mechanical ventilation than were patients with C. jejuni—related GBS (0 of 9 patients vs. 7 of 12 patients; P=.014). Furthermore, patients with influenza A—related GBS were more likely to have preceding ILS and/or RTI (8 of 9 vs. 15 of 41; P=.015) and had a significantly longer duration between the infectious event and GBS onset (median, 15 days vs. 6.5 days; P=.040), compared with patients with GBS due to an unidentified agent who had negative influenza CFT results.

Table 2
View larger version:
Table 2

Analysis of influenza A—related Guillain-Barré syndrome (GBS), compared with GBS caused by Campylobacter jejuni and with GBS caused by an unidentified agent.

Previous SectionNext Section

Discussion

To our knowledge, this study is the first to provide evidence that influenza viruses are triggering agents of GBS. This was determined in 2 stages. First, we established a statistical link between cases of GBS unrelated to usual etiologies (i.e., C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae) and cases of ILI in the French population; the incidence of ILI was notably high during the month before the peak number of admissions to our health care center for GBS caused by an unidentified agent. Second, we sought virological evidence of recent infection due to influenza A or B viruses in patients with GBS that had occurred within periods of positive association with epidemic ILI. Indeed, although ILI may be caused by numerous infectious agents, epidemics of influenza represent the most common etiology. Although it is time consuming, CFT was chosen to screen patients' samples for recent influenza. Indeed, CFT preferentially detects IgM and provides a particularly reliable means to detect recent viral infection [24–27]. This screening approach was then confirmed by strain-specific HIAs for cases related to influenza A virus.

The role of influenza viruses as triggering agents of GBS in our study is consistent with that in a recent nested case-control study, based on data from the United Kingdom General Practice Research Database during 1991–2001, which found a positive association between GBS and a number of infectious events (including Campylobacter infection, Epstein-Barr virus infection, and ILI) during the 2 months preceding GBS onset [28]. This is also consistent with some anecdotal cases of GBS or GBS-related diseases that occurred after influenza, although these cases were mainly reported in pediatric patients [29, 30]. However, our data reveal that cases of influenza-related GBS occur relatively infrequently, and this may explain why no previous study has yet proved a direct link between influenza and GBS. In our study, of 405 patients with GBS who were hospitalized from 1996 through 2004, only 14 (3.5%) had evidence of recent influenza. Moreover, most cases were grouped within seasons of high influenza activity. Eight of 10 influenza A—related cases were detected during only 2 of the 8 influenza seasons covered by the study.

With consideration that the number of cases of clinical influenza per year in the greater Paris area was ∼300,000 during seasons 1996–1997 and 1999–2000 and that our health care center handles 20%–30% of GBS cases per year in the same area [5], it can be estimated that the incidence of influenza-related GBS relative to the number of cases of influenza is 4–7 cases of GBS per 100,000 cases of influenza. In comparison, the risk of developing GBS after C. jejuni infection has been estimated to be 1 case of GBS per 1000 cases of C. jejuni infection [31], which suggests that influenza viruses may either be poorly powerful GBS triggers or require specific host-susceptibility to trigger GBS.

Cases of GBS associated with influenza—more specifically, those involving influenza A viruses—appear to constitute a specific entity. Indeed, influenza A—related cases differed from other cases in our study: they involved a longer duration from the infectious event (most frequently ILS or RTI) to GBS onset (median, 15 days) and an absence of antiganglioside antibody response. None of these patients required mechanical ventilation, most had demyelinating or equivocal electrophysiological profiles, and none had an axonal profile. Our results are consistent with previous studies that revealed a longer time before GBS onset when it was preceded by acute respiratory infection than when it was preceded by GI and a less frequent requirement for mechanical ventilation in cases unrelated to C. jejuni, cytomegalovirus, Epstein-Barr virus, or M. pneumoniae [31, 32]. This suggests that there are specific immunopathological events leading from influenza A to GBS, possibly involving an autoimmune response to viral peptides, as has been suggested for cytomegalovirus [4].

Whether certain viral strains or subtypes have a greater ability than others to induce GBS remains an unanswered question. Most influenza A—related cases identified in our study involved H3N2 viruses, which were the prevalent subtypes involved in the 2 major influenza seasons of the study period (A/Nanchang/933/95 during 1996–1997 and A/Sydney/5/97 during 1999–2000). Thus, most influenza virus infections were caused by H3N2 viruses; this may explain the proportionally high number of GBS cases related to H3N2 virus in our study. The proportion of cases found to be related to influenza A virus (10 cases) or to influenza B virus (4 cases), consistent with the respective prevalence of the 2 viruses in the studied influenza seasons, also argues for similar propensities of different influenza viruses to induce GBS. However, this does not preclude strain-specific traits possibly implicated in the genesis of GBS. Recent studies seem to indicate that the immune response triggered by influenza A virus is strain dependent [33].

The link between GBS and influenza has long been viewed as a link between GBS and influenza vaccination on the basis of the report of an abnormally high number of GBS cases during the mass vaccination campaign against swine influenza in the United States during 1976–1977 [6]. Our study demonstrates that there is also a risk of GBS after influenza virus infection in adults, with an expected frequency much higher than that after influenza vaccination using either inactivated vaccines (1 GBS case per 1,000,000 vaccinated persons [34–36]) or live attenuated vaccines (2 GBS cases per 2,500,000 vaccinated persons [37]). Tam et al. [28] recently provided evidence that influenza vaccination might actually protect against GBS. These authors pointed out that this finding was not inconsistent with an absolute increase in GBS risk after vaccination but that it indicated a smaller risk than that after influenza. Influenza vaccination is highly recommended and freely administered in France to individuals aged >65 years. In our study, most of the patients with influenza-related GBS were aged <65 years, and this might be related to a protective effect of influenza vaccination. In addition to allowing avoidance of severe complications associated with influenza, influenza vaccination may thus protect against GBS and its long-term sequelae.

Previous SectionNext Section

Acknowledgments

We thank Isabelle Senegas and Vanessa Roca, for assistance, and Antoine Flahaut, for helpful discussion.

Financial support. Laboratoire Français du Fractionnement et des Biotechnologies.

Potential conflicts of interest. All authors: no conflicts.

  • Received June 3, 2009.
  • Revision received August 24, 2009.
Previous Section
 

References

  1. ↵
    1. Hadden RD,
    2. Karch H,
    3. Hartung HP,
    4. et al
    . Preceding infections, immune factors, and outcome in Guillain-Barré syndrome. Neurology 2001;56:758-65.
    Abstract/FREE Full Text
  2. ↵
    1. Hughes RA,
    2. Cornblath DR
    . Guillain-Barré syndrome. Lancet 2005;366:1653-66.
    CrossRefMedlineWeb of Science
  3. ↵
    1. Kuwabara S
    . Guillain-Barré syndrome: epidemiology, pathophysiology and management. Drugs 2004;64:597-610.
    CrossRefMedlineWeb of Science
  4. ↵
    1. Hughes RA,
    2. Hadden RD,
    3. Gregson NA,
    4. Smith KJ
    . Pathogenesis of Guillain-Barré syndrome. J Neuroimmunol 1999;100:74-97.
    CrossRefMedlineWeb of Science
  5. ↵
    1. Sivadon-Tardy V,
    2. Orlikowski D,
    3. Rozenberg F,
    4. et al
    . Guillain-Barré syndrome, greater Paris area. Emerg Infect Dis 2006;12:990-3.
    MedlineWeb of Science
  6. ↵
    1. Langmuir AD,
    2. Bregman DJ,
    3. Kurland LT,
    4. Nathanson N,
    5. Victor M
    . An epidemiologic and clinical evaluation of Guillain-Barré syndrome reported in association with the administration of swine influenza vaccines. Am J Epidemiol 1984;119:841-79.
    Abstract/FREE Full Text
  7. ↵
    1. Tam CC
    . Influenza, Campylobacter and Mycoplasma infections, and hospital admissions for Guillain-Barré syndrome, England. Emerg Infect Dis 2006;12:1880-7.
    MedlineWeb of Science
  8. ↵
    1. Durand MC,
    2. Lofaso F,
    3. Lefaucheur JP,
    4. et al
    . Electrophysiology to predict mechanical ventilation in Guillain-Barré syndrome. Eur J Neurol 2003;10:39-44.
    CrossRefMedlineWeb of Science
  9. ↵
    1. Durand MC,
    2. Prigent H,
    3. Sivadon-Tardy V,
    4. et al
    . Significance of phrenic nerve electrophysiological abnormalities in Guillain-Barré syndrome. Neurology 2005;65:1646-9.
    Abstract/FREE Full Text
    1. Durand MC,
    2. Porcher R,
    3. Orlikowski D,
    4. et al
    . Clinical and electrophysiological predictors of respiratory failure in Guillain-Barré syndrome: a prospective study. Lancet Neurol 2006;5:1021-8.
    CrossRefMedlineWeb of Science
  11. ↵
    1. Orlikowski D,
    2. Sharshar T,
    3. Porcher R,
    4. Annane D,
    5. Raphael JC,
    6. Clair B
    . Prognosis and risk factors of early onset pneumonia in ventilated patients with Guillain-Barré syndrome. Intensive Care Med 2006;32:1962-9.
    CrossRefMedlineWeb of Science
  12. ↵
    1. Asbury AK,
    2. Cornblath DR
    . Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol 1990;27(Suppl):21-4.
    CrossRef
  13. ↵
    1. Chabraoui F,
    2. Derrington EA,
    3. Mallie-Didier F,
    4. Confavreux C,
    5. Quincy C,
    6. Caudie C
    . Dot-blot immunodetection of antibodies against GM1 and other gangliosides on PVDF-P membranes. J Immunol Methods 1993;165:225-30.
    CrossRefMedlineWeb of Science
  14. ↵
    Sentinelle. Available at: http://websenti.b3e.jussieu.fr/sentiweb/?lang=en. Accessed 14 November 2008.
  15. ↵
    Groupes Régionaux d'Observation de la Grippe. Available at: http://www.grog.org. Accessed 14 November 2008.
  16. ↵
    1. Altman DG
    . Practical statistics for medical research. London: Chapman and Hall/CRC Press; 1991. p. 283. 433-5.
  17. ↵
    1. Hubert B,
    2. Watier L,
    3. Garnerin P,
    4. Richardson S
    . Meningococcal disease and influenza-like syndrome: a new approach to an old question. J Infect Dis 1992;166:542-5.
    Abstract/FREE Full Text
  18. ↵
    1. Jones RH,
    2. Ford PM,
    3. Hamman RF
    . Seasonality comparisons among groups using incidence data. Biometrics 1988;44:1131-44.
    CrossRefMedlineWeb of Science
  19. ↵
    1. Hochberg Y
    . A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988;75:800-3.
    Abstract/FREE Full Text
  20. ↵
    1. Kendal AP,
    2. Joseph JM,
    3. Kobayashi G,
    4. et al
    . Laboratory-based surveillance of influenza virus in the United States during the winter of 1977–1978. I. Periods of prevalence of H1N1 and H3N2 influenza A strains, their relative rates of isolation in different age groups, and detection of antigenic variants. Am J Epidemiol 1979;110:449-61.
    Abstract/FREE Full Text
  21. ↵
    1. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group
    . Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Lancet 1997;349:225-30.
    CrossRefMedlineWeb of Science
  22. ↵
    1. Hadden RD,
    2. Cornblath DR,
    3. Hughes RA,
    4. et al
    . Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Ann Neurol 1998;44:780-8.
    CrossRefMedlineWeb of Science
  23. ↵
    1. Manuguerra JC,
    2. Mosnier A
    . Surveillance of influenza in Europe from October 1999 to February 2000. Euro Surveill 2000;5:63-8.
    Medline
  24. ↵
    1. Buchner YI,
    2. Heath RB,
    3. Collins JV,
    4. Pattison JR
    . Serum IgM antibody and influenza A infection. J Clin Pathol 1977;30:723-7.
    Abstract/FREE Full Text
    1. Oswald NC,
    2. Jones MC,
    3. Yealland SJ
    . A review of routine tests for respiratory viruses in hospital inpatients. Thorax 1975;30:361-6.
    Abstract/FREE Full Text
    1. Playford EG,
    2. Dwyer DE
    . Laboratory diagnosis of influenza virus infection. Pathology 2002;34:115-25.
    CrossRefMedlineWeb of Science
  27. ↵
    1. van Wissen M,
    2. Keller TT,
    3. Ronkes B,
    4. et al
    . Influenza infection and risk of acute pulmonary embolism. Thrombosis J 2007;5:16.
    CrossRef
  28. ↵
    1. Tam CC,
    2. O'Brien SJ,
    3. Petersen I,
    4. Islam A,
    5. Hayward A,
    6. Rodrigues LC
    . Guillain-Barré syndrome and preceding infection with Campylobacter, influenza and Epstein-Barr virus in the general practice research database. PLoS ONE 2007;2:e344.
    CrossRefMedline
  29. ↵
    1. Matsumoto H,
    2. Kobayashi O,
    3. Tamura K,
    4. Ohkawa T,
    5. Sekine I
    . Miller Fisher syndrome with transient coma: comparison with Bickerstaff brainstem encephalitis. Brain Dev 2002;24:98-101.
    CrossRefMedlineWeb of Science
  30. ↵
    1. Migita M,
    2. Matsumoto T,
    3. Fujino O,
    4. Takaishi Y,
    5. Yuki N,
    6. Fukunaga Y
    . Two cases of influenza with impaired ocular movement. Eur J Paediatr Neurol 2001;5:83-5.
    CrossRefMedline
  31. ↵
    1. Yuki N
    . Infectious origins of, and molecular mimicry in, Guillain-Barré and Fisher syndromes. Lancet Infect Dis 2001;1:29-37.
    CrossRefMedline
  32. ↵
    1. Van Koningsveld R,
    2. Van Doorn PA,
    3. Schmitz PI,
    4. Ang CW,
    5. Van der Meche FG
    . Mild forms of Guillain-Barré syndrome in an epidemiologic survey in The Netherlands. Neurology 2000;54:620-5.
    Abstract/FREE Full Text
  33. ↵
    1. Hayman A,
    2. Comely S,
    3. Lackenby A,
    4. et al
    . Variation in the ability of human influenza A viruses to induce and inhibit the IFN-β pathway. Virology 2006;347:52-64.
    CrossRefMedlineWeb of Science
  34. ↵
    1. Haber P,
    2. DeStefano F,
    3. Angulo FJ,
    4. et al
    . Guillain-Barré syndrome following influenza vaccination. JAMA 2004;292:2478-81.
    Abstract/FREE Full Text
    1. Juurlink DN,
    2. Stukel TA,
    3. Kwong J,
    4. et al
    . Guillain-Barré syndrome after influenza vaccination in adults: a population-based study. Arch Intern Med 2006;166:2217-21.
    Abstract/FREE Full Text
  36. ↵
    1. Lasky T,
    2. Terracciano GJ,
    3. Magder L,
    4. et al
    . The Guillain-Barré syndrome and the 1992–1993 and 1993–1994 influenza vaccines. N Engl J Med 1998;339:1797-802.
    CrossRefMedlineWeb of Science
  37. ↵
    1. Izurieta HS,
    2. Haber P,
    3. Wise RP,
    4. et al
    . Adverse events reported following live, cold-adapted, intranasal influenza vaccine. JAMA 2005;294:2720-5.
    Abstract/FREE Full Text
| Table of Contents

This Article

  1. Clin Infect Dis. (2009) 48 (1): 48-56. doi: 10.1086/594124
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most