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.