Could Parkinson's disease follow intra-uterine influenza?: a speculative hypothesis

Patients with idiopathic Parkinson's disease do not appear to be distributed smoothly with respect to year of birth. Individuals born within the years 1892, 1904, 1909, 1918, 1919 and 1929 appear to have had an increased risk of developing idiopathic Parkinson's disease in later life. These years are close to those of the influenza pandemics of the period 1890-1930. The estimated risk of an individual developing idiopathic Parkinson's disease shows a significant correlation with the crude influenza mortality for the year of his birth, within the range 1900 to 1930. It is suggested that intra-uterine influenza may be cytotoxic to the developing foetal substantia nigra, and that an affected individual may be born without evident disability but with limited striatal neurochemical reserves and a reduced nigral cell count. In later life normal cellular involution with ageing or exposure to environmental neurotoxic factors may further erode these reserves to a level where the substantia nigra fails and idiopathic Parkinson's disease becomes clinically apparent.