IMPORTANCE Epstein-Barr virus and its acute manifestation, infectious mononucleosis (IM), are associated with an increased risk of multiple sclerosis (MS). Whether this association is confounded by susceptibility to infection is still debated.

The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively. However, whether this extends to infections in a broader sense is less clear and little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections, such as of the CNS. This study aims to assess if hospital-diagnosed infections by type and site before age 20 years are associated with risk of a subsequent multiple sclerosis diagnosis and whether this association is explained entirely by infectious mononucleosis, pneumonia, and CNS infections. Individuals born in Sweden between 1970–1994 were identified using the Swedish Total Population Register (n = 2,422,969). Multiple sclerosis diagnoses from age 20 years and hospital-diagnosed infections before age 20 years were identified using the Swedish National Patient Register. Risk of a multiple sclerosis diagnosis associated with various infections in adolescence (11–19 years) and earlier childhood (birth-10 years) was estimated using Cox regression, with adjustment for sex, parental socioeconomic position, and infection type. None of the infections by age 10 years were associated with risk of a multiple sclerosis diagnosis. Any infection in adolescence increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.33, 95% confidence interval 1.21–1.46) and remained statistically significant after exclusion of infectious mononucleosis, pneumonia, and CNS infection (hazard ratio 1.17, 95% confidence interval 1.06–1.30). CNS infection in adolescence (excluding encephalomyelitis to avoid including acute disseminated encephalitis) increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.85, 95% confidence interval 1.11–3.07). The increased risk of a multiple sclerosis diagnosis associated with viral infection in adolescence was largely explained by infectious mononucleosis. Bacterial infections in adolescence increased risk of a multiple sclerosis diagnosis, but the magnitude of risk reduced after excluding infectious mononucleosis, pneumonia and CNS infection (hazard ratio 1.31, 95% confidence interval 1.13–1.51). Respiratory infection in adolescence also increased risk of a multiple sclerosis diagnosis (hazard ratio 1.51, 95% confidence interval 1.30–1.75), but was not statistically significant after excluding infectious mononucleosis and pneumonia. These findings suggest that a variety of serious infections in adolescence, including novel evidence for CNS infections, are risk factors for a subsequent multiple sclerosis diagnosis, further demonstrating adolescence is a critical period of susceptibility to environmental exposures that raise the risk of a multiple sclerosis diagnosis. Importantly, this increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, or CNS infections.

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Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative neurological disease. 1 It is the most common form of motor neuron disease (MND), but still considered rare, with a global incidence of approximately 2/100,000 persons. 2 ALS onset typically occurs in later life, peaking between 50 and 75 years of age, affecting persons of both sexes and all ethnicities. 1 The consequences of ALS can be devastating for those affected and their families. Disease progression is rapid, with only half of patients living longer than three years following diagnosis. 3

Background: Evidence for the association between body mass index (BMI) and multiple sclerosis (MS) among men remains mixed. Objective and methods: Swedish military conscription and other registers identified MS after age of 20 years and BMI at ages 16–20 years ( N = 744,548). Results: Each unit (kg/m2) BMI increase was associated with greater MS risk (hazard ratio and 95% confidence interval = 1.034, 1.016–1.053), independent of physical fitness (1.021, 1.001–1.042). Categorised, overweight and obesity were associated with statistically significant raised MS risk compared to normal weight, but not after adjustment for physical fitness. Conclusion: MS risk rises with increasing BMI, across the entire BMI range.