Purpose: To validate the diagnostic codes for Guillain-Barré syndrome (GBS) in the Danish National Patient Registry (DNPR). Secondly, to examine 30-year trends in the incidence of GBS in Denmark. Patients and methods: We used the DNPR to identify all patients aged 16 and above diagnosed with a primary GBS diagnosis at any Danish department of neurology between 1987 and 2016. Medical files were reviewed according to the clinical criteria of the National Institute of Neurological Disorders and Stroke Committee and classified according to the Brighton criteria. The incidence rate (IR) was calculated based on data from 1987 to 2016 and stratified by season, gender, and age. Results: Over 30 years, we identified 2,319 patients aged 16 and above in the DNPR. From a validation cohort of 573 patients, we were able to retrieve 425 (74.2%) medical files; 356 GBS diagnoses were confirmed. The overall positive predictive value was 83.8% (95% confidence interval (CI): 80.0–87.0). In 99% of the confirmed patients, the Brighton criteria level 1–3 for GBS were met. The IR was fairly stable over 30 years at 1.77 per 100,000 person years (95% CI: 1.70–1.84). The incidence was higher in the winter season (IR ratio compared with summer: 1.18 (95% CI: 1.09–1.29)), and was strongly associated with male gender (IR ratio vs females: 1.44 (95% CI: 1.33–1.57)). IRs rose with age at diagnosis, particularly after the age of 50 in both men and women and a minor peak was observed for total IR in young adults. Conclusion: Primary diagnostic codes for GBS at Danish departments of neurology have high validity. The DNPR is a well-suited data source for epidemiological research on GBS. The Danish nationwide 30-year GBS IR is stable over time and similar to GBS IRs reported in other European and North American populations.

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Objective:To determine whether hospital-diagnosed and community-treated infections are important Guillain-Barré syndrome (GBS) risk factors, we investigated the magnitude and duration of associated GBS risk.Methods:We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 1987 and 2016 and 10 matched population controls per case. Hospital-diagnosed infections were determined in the period 1987 to 2016, and community antibiotic prescriptions in the period 2004 to 2016. We used conditional logistic regression to examine the relative risk of GBS associated with having a recent infection.Results:Hospital-diagnosed infections within 60 days were observed in 4.3% of 2,414 GBS cases versus 0.3% of 23,909 controls, with a matched odds ratio (OR) of 13.7 (95% CI, 10.2-18.5). The strongest association with subsequent GBS was observed for lower respiratory tract infection, gastrointestinal tract infection, and septicemia. Community antibiotic prescriptions within 60 days were observed in 22.4% of 1,086 GBS cases and 7.8% of 10,747 controls, with a matched OR of 3.5 (95% CI, 3.0-4.1). The risk of GBS declined considerably with time since infection, with high ORs of 21.3 (95% CI, 14.5-31.2) and 4.7 (95% CI, 3.9-5.7) observed within the first month after a hospital-diagnosed infection and a community antibiotic prescription, respectively. However, GBS risk remained increased 2.4-fold (95% CI, 1.1-5.5) and 1.5-fold (95% CI, 1.2-2.0) even in the fifth month after infection.Conclusion:There is a strong, temporal association between community antibiotic use and especially infections necessitating hospitalization and risk of subsequent GBS.

Background and objectives:Cancer may increase the risk of developing Guillain-Barré syndrome (GBS) due to molecular mimicry or immunosuppression, but the exact relationship is unclear. We aimed to determine the association between incident cancer and the following risk of GBS development.Methods:We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 1987 and 2016 and 10 age, sex and index date-matched population controls per case. We identified incident cancer diagnoses between six months prior to and two months after the GBS index date. We used conditional logistic regression to compute ORs as a measure of relative risk and performed stratified analyses to assess the impact of cancer on GBS risk in strata of calendar-periods, sex and age. In sensitivity analyses, to assess any potential risk of survival bias induced by including cancer diagnoses potentially made after GBS diagnosis, we examined incident cancers in both a broader exposure window (one year before to three months after GBS index date) and a narrower window (six months to one month before the GBS index date).Results:Of the 2,414 patients with GBS and 23,909 controls included, 49 cases (2.0%) and 138 controls (0.6%) had a recent cancer diagnosis, respectively, yielding a matched odds ratio (OR) of 3.6 (95% confidence interval (CI), 2.6- 5.1) for GBS associated with cancer. Stratification by calendar time, gender and age showed robust results for the association between cancer and GBS, with no major variations. Broadening and narrowing the exposure window produced slightly weakened associations of OR, 2.4 (95% CI, 1.8-3.3) and OR, 2.5 (95% CI, 1.5-4.1), respectively. The GBS ORs were highest for cancers of the lymphatic and hematopoietic tissue (OR, 7.2; 95% CI, 2.9-18.0), respiratory tract (OR, 5.6; 95% CI, 2.7-11.9), prostate and other male genital organ (OR, 5.0; 95% CI, 2.1-11.6) and breast cancer (OR, 5.0; 95% CI, 1.7-14.5).Discussion:In this large nationwide epidemiologic study, incident cancer was associated with a markedly increased risk of subsequent GBS development. The results suggest that yet unidentified factors present in several types of cancer drive this association.