Onset Of Guillain-Barré Syndrome Research Articles

Temporal profile of anti-ganglioside antibodies and their relation to clinical parameters and treatment in Guillain–Barré syndrome

Elevated anti-ganglioside antibody levels mainly of anti-GM1 and anti-GD1a specificities have been reported in THE serum of patients with Guillain–Barré syndrome (GBS). The relevance of anti-ganglioside antibodies other than anti-GM1 and anti-GD1a IgG antibodies and the temporal profile of anti-ganglioside antibodies in GBS is less clear. We studied serum antibodies to GM1, GD1a, GD1b, GQ1b, sulfatide and cardiolipin of the IgM, IgG and IgA classes over the course of GBS in patients who were untreated or treated with highdose intravenous immunoglobulin (IvIg). Antibodies to GD1b, GQ1b, sulfatide and cardiolipin were not detected in the sera of the GBS patients examined in this study. Anti-GM1 IgG titers peaked around 40 days and anti-GD1a IgM around 90 days after GBS onset. Titers of anti-GM1 IgG antibodies decreased following IvIg treatment. Patients with antibody peaks, defined as fivefold or higher increase in antibody titer compared to the lowest antibody titer over the course of GBS, had higher disability scores during the first two weeks of GBS and a worse clinical outcome (anti-GM1 IgG and anti-GD1a IgM antibody peaks) and axonal damage (anti-GD1a IgM antibody peaks), compared to patients without peak antibody titers. Anti-GM1 IgG and anti-GD1a IgM antibodies are thus strongly associated with more severe- and predominantly axonal cases of GBS. The appearance of anti-GM1 IgG and anti-GD1a antibody peaks in the serum after the termination of the acute phase of GBS suggests that these antibodies are produced secondary to nerve damage in GBS. The data does not exclude the possibility that secondarily secreted anti-GM1 IgG and anti-GD1a IgM antibodies may themselves be biologically active and play a role in disease propagation and/or recovery from disease in some patients with GBS.

Guillain-Barr� syndrome accompanied by central nervous system lupus in a patient with juvenile rheumatoid arthritis

We describe a 17-year-old female with juvenile rheumatoid arthritis accompanied by Guillain-Barré syndrome (GBS) during the course of central nervous system (CNS) lupus. She initially developed CNS lupus, including headache and convulsion. A high-signal area in a magnetic resonance scan of her brain with T2-weighted images was noted, and her cerebrospinal fluid exhibited increased levels of IgG and interleukin-6. Eighteen days after the onset of CNS lupus, polyneuropathy in the lower extremities developed, and a diagnosis of GBS was made. No obvious preceding infections in the upper respiratory or gastrointestinal systems were noted before the onset of GBS, indicating that GBS might be part of the symptoms of CNS lupus.

Guillain-Barre syndrome and Campylobacter jejuni infection

Guillain-Barre syndrome (GBS) is the most common cause of acute neuromuscular paralysis, usually due to acute inflammatory demyelinating polyradiculoneuropathy. The presence of activated T lymphocytes and antibodies against peripheral nerve myelin suggests an autoimmune pathogenesis, although there is wide heterogeneity. Gangliosides are sialylated glycolipids widely distributed in nervous system membranes. GBS is usually preceded by an infection, most frequently Campylobacter jejuni enteritis, but also cytomegalovirus, Mycoplasma pneumoniae or Epstein-Barr virus. Patients with GBS and C. jejuni infection are more likely to have neurophysiological features of axonal neuropathy, antibodies to ganglioside GM1, pure motor GBS, a less elevated CSF protein concentration and a worse outcome than other GBS patients. Although molecular mimicry between peripheral nerve gangliosides and epitopes present on C. jejuni lipopolysaccharide could explain some of these associations, this hypothesis is inadequate to account for many aspects of the pathogenesis of GBS.

Risk of Guillain-Barré syndrome after measles-mumps-rubella vaccination

Objective: To assess the postulated causal association between measles-mumps-rubella (MMR) vaccination and Guillain-Barré syndrome (GBS). Study Design: Active retrospective study based on linkage of the nationwide hospital discharge register with individual vaccination records. All patients hospitalized for treatment of GBS in Finland between November 1982 and December 1986 were included in the study. Results: During the study period, 189 patients were hospitalized for treatment of GBS, and ~630,000 vaccine recipients received 900,000 doses of MMR vaccine; 24 of the 189 patients represented the prevailing target population for MMR vaccination, of whom 20 were vaccinated. MMR vaccination did not cause any increase over the background incidence of GBS, and no clustering of cases of GBS occurred at any time point after administration of MMR vaccine. The interval between vaccination and onset of symptoms of GBS exceeded the designated risk period of 6 weeks in all cases, varying from 80 days to years. MMR vaccination after recovery from GBS did not cause relapses of the illness. Respiratory or gastrointestinal tract infection predated the onset of GBS by 3 to 30 days in 20 (83%) of the 24 patients. Conclusions: No causal association seems to prevail between MMR vaccination and GBS. (J Pediatr 2001;138:250-4)

Risk factors for Guillain-Barré syndrome: a population-based case-control study. Emilia-Romagna Study Group on Clinical and Epidemiological Problems in Neurology.

We performed the first population-based case-control study on clinical risk factors and drug exposure in Guillain-Barré syndrome (GBS). Sixty patients with GBS were collected through an incidence survey performed in the Emilia-Romagna region of northern Italy. GBS patients were compared with 109 hospital controls (HC) and 59 population controls (PC) as for clinical events and drug exposure during the month preceding the study inclusion. Comparison of HC with PC showed no significant difference in the frequency of clinical events which occurred during the preceding month. This indicated that our HC were well representative of the general population for the risk factors investigated. GBS patients were compared with HC or both HC and PC using both univariate and multivariate analysis. Univariate analysis showed a significant association with fever and upper airway infection symptoms occurring in the preceding month. Furthermore, a significantly higher exposure to antibiotics, antipyretics/analgesics, and gangliosides was observed. However, multivariate analysis showed that only fever was significantly related to GBS onset (OR 28, 95% CI 5.2-313 for GBS vs. HC; OR 29, 95% CI 7.0-256 for GBS vs. HC and PC).

Guillain–Barré and Fisher's syndromes subsequent to Campylobacter jejuni enteritis are associated with HLA-B54 and Cw1 independent of anti-ganglioside antibodies

The frequencies of human leukocyte antigens (HLA)-class I (A, B and Cw) were determined serologically and those of HLA-class II (DRB1 and DQB1) at the genomic level in 35 Japanese patients with Guillain–Barré syndrome (GBS), 58 with Fisher's syndrome (FS), and 112 healthy controls. HLA-B54 and -Cw1 antigens were found in GBS and FS patients from whom Campylobacter jejuni had been isolated more often than found in the healthy controls. No HLA types were related to GBS or FS as a whole, except for the B54 antigen which often was significant in the entire GBS group. This relation, however, may depend on the high population of C. jejuni-isolate patients in our GBS group. There were no relationships between the frequencies of HLA types and the presence of serum IgG antibodies to GM1, GQ1b, GD1a, or GalNAc-GD1a. Our findings suggest that HLA types are associated with the onset of GBS and FS after C. jejuni enteritis and that the HLA types in distinct GBS and FS subgroups of a single etiological origin need to be examined.

Temporal association between the isolation of Sabin-related poliovirus vaccine strains and the Guillain-Barré syndrome

Thirty eight paralysis cases classified as Guillain-Barré syndrome (GBS) in Brazil were analysed. In all these cases Sabin-related poliovirus vaccine strains were isolated. In most of the cases the last vaccine dose was given months or years before the onset of GBS, suggesting a persistent infection or the transmission of the Sabin-related strains to the patients. The isolation of Sabin-related strains from GBS cases some days or weeks after the onset of the disease, demonstrated a temporal association between the isolation of the strains and the disease. Although the isolates from the GBS cases may not be the etiological agent of the disease, this study strongly indicates that infections caused by Sabin-related vaccine strains can trigger the GBS in certain cases.

N‐acetylgalactosaminyl GD1a is a target molecule for serum antibody in Guillain‐Barré syndrome

Serum antibodies against such major glycolipids as GM1, GD1b, and LM1 have been reported in patients in the acute phase of Guillain-Barré syndrome (GBS). Because minor unidentified glycolipids also may be targets of antibodies in GBS sera, we assayed serum antibody against a crude ganglioside fraction using thin-layer chromatogram immunostaining. Antibody activity was detected against a band that migrated just below GD1a in 6 of the 50 patients with GBS tested. Antibody titer, as determined by enzyme-linked immunosorbent assay, decreased during the course of the disease. All 6 patients had suffered gastrointestinal infection before the neurological onset of GBS and showed low amplitudes for the compound muscle action potentials and normal or only slightly decreased nerve conduction velocities. Thin-layer chromatogram immunostaining did not show this antibody activity in any of the 16 normal and 119 disease controls. The unidentified glycolipid was isolated by DEAE-Sephadex A-25 column chromatography, sialidase treatment, and Iatrobeads column chromatography. Fast atom bombardment-mass spectra showed it to be N-acetyl-galactosaminyl GD1a.

ROLE OF INFECTION DUE TO CAMPYLOBACTER JEJUNI IN THE INITIATION OF GUILLAIN-BARRE SYNDROME

Recent reports suggest that infection with Campylobacter jejuni, a common enteric pathogen, may cause Guillain-Barre syndrome (GBS) by triggering demyelination of peripheral nerves. GBS is preceded by an acute infectious illness (due to a variety of agents) in 50%-75% of cases; the onset of neurological symptoms is preceded by diarrhea in 10%-30% of cases. In the last decade, more than 20 published anecdotal reports and case series have described patients with C. jejuni infection documented 1-3 weeks before onset of GBS. Cultures of fecal samples obtained at the onset of neurological symptoms from patients with GBS have yielded C. jejuni in more than 25% of cases. A relatively rare serotype, Penner type O19, is overrepresented among isolates of C. jejuni from Japanese patients with GBS. Serological studies suggest that 20%-40% of patients with GBS have evidence of recent C. jejuni infection. In summary, infection with C. jejuni is a common antecedent to GBS and probably plays a role in initiating demyelination; although several pathogenic mechanisms are possible, none has been proven.

Role of Infection Due to Campylobacter jejuni in the Initiation of Guillain-Barre Syndrome

Recent reports suggest that infection with Campylobacter jejuni, a common enteric pathogen, may cause Guillain-Barré syndrome (GBS) by triggering demyelination of peripheral nerves. GBS is preceded by an acute infectious illness (due to a variety of agents) in 50%-75% of cases; the onset of neurological symptoms is preceded by diarrhea in 10%-30% of cases. In the last decade, more than 20 published anecdotal reports and case series have described patients with C. jejuni infection documented 1-3 weeks before onset of GBS. Cultures of fecal samples obtained at the onset of neurological symptoms from patients with GBS have yielded C. jejuni in more than 25% of cases. A relatively rare serotype, Penner type O19, is overrepresented among isolates of C. jejuni from Japanese patients with GBS. Serological studies suggest that 20%-40% of patients with GBS have evidence of recent C. jejuni infection. In summary, infection with C. jejuni is a common antecedent to GBS and probably plays a role in initiating demyelination; although several pathogenic mechanisms are possible, none has been proven.

Incidence of the Guillain-Barré Syndrome in Ferrara, Northern Italy, 1981–1987

The few incidence estimates on Guillain-Barré syndrome (GBS) in Italy indicate rates lower than the values provided by other previous non-Italian population-based studies. The latter range from 0.6 to 1.9 cases per 100,000 population per year. To verify whether Italy may be considered a low-risk area for GBS we studied the incidence of the disease in Local Health Unit No. 31 (USL 31) of Ferrara, Northern Italy (mean population 180,701 inhabitants) for the years 1981-1987. The annual incidence rates were stable during this period with an average incidence of 1.26 cases per 100,000 population per year. No significant difference was found for urban or rural residence and there was no significant seasonal clustering. In 37.5% of the series an antecedent infection was recorded within 4 weeks before GBS onset. The survey seems to support the hypothesis of a homogeneous distribution of GBS in space and time and does not support the notion that GBS is less common in Italy than elsewhere.

Guillain-Barré syndrome in Western Australia, 1980-1985.

A clinicoepidemiological study of 109 patients with Guillain-Barré syndrome who were admitted to the four major teaching hospitals in Perth between January 1, 1980 and December 31, 1985 was conducted through the Hospital Morbidity Data System. The annual incidence rate of Guillain-Barré syndrome was 1.35 cases per 100,000 population. The age-adjusted incidence rates were 1.49 cases per 100,000 men and 1.20 cases per 100,000 women. A minor peak in the sex-adjusted incidence rate was present in young adult life with a larger peak in later life. Twenty-two (20%) patients presented in the five-month period from July 1984 to November 1984 (P less than 0.05) but a common infectious agent or geographical area of residence was not discovered during this period. Immune function had been affected potentially before the onset of Guillain-Barré syndrome in 12 (11%) patients, which raises further speculation as to the role of immunological mechanisms in the pathogenesis of Guillain-Barré syndrome. In order to enhance our understanding of this disorder, it is recommended that an assessment of immune function be considered in cases of Guillain-Barré syndrome and also chronic inflammatory demyelinating polyneuropathy.

National surveillance for Guillain-Barré syndrome: January 1978-March 1979.

Between January 1, 1978, and March 31, 1979, 1,034 cases of Guillain-Barré syndrome (GBS) were reported to the Centers for Disease Control by the 1,813 American Academy of Neurology sentinel physicians who participated in the national GBS surveillance program. A direct correlation was observed between increasing age and the age-specific attack (incidence) rates. Based on the cases observed and the total US population, age-adjusted attack rates were statistically higher in males (0.52 per 100,000) than in females (0.40). Rates for whites were 0.44 and those for blacks 0.28 per 100,000; although the difference is statistically significant, uncertainties as to the true denominators by race preclude acceptance of these differences as valid. Sixty-seven percent, or 682 of the patients, reported that they had had an antecedent illness within 8 weeks before onset of GBS, and among them the peak period of onset of GBS was in the second week after the onset of the prior illness. There were also 52 patients (5%) who had undergone surgery and 45 (4.5%) who had received vaccinations, both within the 8 weeks before onset of GBS. However, the high proportions of antecedent illness in these groups (45% of those operated and 53% of those vaccinated) made attribution of GBS to the procedures tenuous. Risk of GBS in patients who reported receiving a swine influenza vaccination in 1976 was no greater than in those who reported that they did not receive this vaccine.

Guillain-Barré syndrome and the 1978-1979 influenza vaccine.

An ongoing surveillance program was intensified to determine whether an increased risk of acquiring vaccine-related Guillain-Barré syndrome (GBS) (similar to that observed after vaccination with the A/New Jersey swine-influenza vaccine in 1976) existed for the approximately 12.5 million adults (greater than or equal to 18 years old) vaccinated in the 1978-1979 influenza campaign. In the contiguous United States (excluding Maryland) 544 cases of GBS with onset between September 1, 1978, and March 31, 1979, were reported, including 12 adults who had been vaccinated within eight weeks before the onset of GBS and 393 who had not. The relative risk of vaccine-associated GBS for adults reported in this surveillance was 1.4 (95% confidence limits, 0.7 to 2.7)--significantly below the risk (6.2) associated with A/New Jersey vaccine for the equivalent eight-week period. In contrast to the A/New Jersey vaccine, the 1978-1979 influenza vaccine was not associated with a statistically significant excess risk of GBS.