Exogenous gangliosides and Guillain-Barré syndrome. An observational study in the local health district of Ferrara, Italy

A retrospective study was carried out in the Ferrara Local Health District, Italy, for the period 1981-1993 (average resident population: 177,235 inhabitants) to establish whether people exposed to exogenous gangliosides had a higher risk of Guillain-Barré syndrome. The incidence of Guillain-Barré syndrome of 1.9/100,000 population/year [95% confidence interval (CI): 1.3-2.5] reported in Ferrara Local Health District in the same period was used as a reference for comparison. The data bank of Ferrara Local Health District made it possible, first to estimate the number of individuals exposed to gangliosides in the resident population of Ferrara Local Health District (3.7%), the number of ganglioside prescriptions and the number of cases of Guillain-Barré syndrome who had treatment with gangliosides (nine patients, 20.9%), and, secondly, to verify the sequence of events between the ganglioside injection and the onset of the disease. Seven of the nine patients (77.8%) received gangliosides as treatment for peripheral neuropathy (Guillain-Barré syndrome onset before gangliosides were prescribed). For the other two patients (22.2%) a possible appropriate temporal sequence between ganglioside injection and onset of Guillain-Barré syndrome was found. Based on two possible ganglioside-related cases, the risk of Guillain-Barré syndrome was higher in the exposed (0.53/100,000 population/month following ganglioside injection; 95% CI: 0.06-1.91) compared with the unexposed population, but the difference was not significant. When only individuals prescribed with mixed gangliosides were considered (both possible ganglioside-related Guillain-Barré syndrome cases received mixed gangliosides), the risk of Guillain-Barré syndrome was higher (0.64/100,000 population/month following ganglioside injection; 95% CI: 0.08-2.31) but the difference from the risk in unexposed individuals was not statistically significant. The relative risk for the exposure to mixed gangliosides was borderline (relative risk = 4.3; 95% CI: 1.0-17.8). The wide 95% confidence intervals were a consequence of sample size limitations. Considering also that the exposed and unexposed groups differed in age (those exposed were older than those unexposed and the age-specific incidence of Guillain-Barré syndrome in the study population increased with increasing age), the present findings question either a strong increased risk of Guillain-Barré syndrome in people exposed to exogenous gangliosides or an immunogenic role of these agents in humans. However, because of the limited sample size, the results are not conclusive.