title: Substantia nigra depigmentation and exposure to encephalitis lethargica.
abstract: OBJECTIVE
  Parkinsonism has occasionally been reported as a consequence of infectious diseases. The present study examines the clinical and pathological correlates of parkinsonism across birth cohorts in relation to critical exposure to the encephalitis lethargica epidemic in the early 1900s.
  
  
  METHODS
  The study population consisted of 678 participants in the Nun Study, of whom 432 died and came to autopsy. Qualitative indices of substantia nigra (SN) depigmentation were verified in a subset of 40 randomly selected subjects using quantitative stereological techniques. SN depigmentation, detected neuropathologically, was correlated with clinical parameters of Parkinson disease, age, and birth cohort.
  
  
  RESULTS
  SN depigmentation was detected in 57 (13.2%) of the cohort. Although qualitative SN depigmentation correlated modestly with age (p = 0.02), it correlated best with birth cohort (p = 0.009) for women born in the years 1895-1899. Quantitative measures of SN depigmentation were increased in this birth cohort compared to age matched subjects from flanking birth cohorts 1890-1894 and 1900-1904 (p < 0.001). SN depigmentation correlated with speed of 6- and 50-foot walk (p < 0.0001), up and go test (p < 0.0001), and hand coordination (p < 0.0001).
  
  
  CONCLUSIONS
  Subjects in the birth cohort 1895-1899 would have been in their late teens and 20s at the onset and during the peak of the encephalitis lethargica epidemic. These were precisely the age ranges of persons who were most often affected by the illness. These data suggest the possibility that the coexistence of parkinsonism and SN depigmentation in this birth cohort may have resulted from the yet undetermined infectious agent responsible for encephalitis lethargica.
authors.affiliation: Department of Neurology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
authors.forename: Nawaz
authors.initials: N
authors.lastname: Hack
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.forename: Annalisa
authors.initials: A
authors.lastname: Abell
authors.forename: Dawson
authors.initials: D
authors.lastname: Dean
authors.forename: Jerrold L
authors.initials: JL
authors.lastname: Vitek
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Berger
mesh_terms: D000369:Aged, 80 and over; D015331:Cohort Studies; D004660:Encephalitis / Q000150:complications / Q000401:mortality / Q000473:pathology*; D005260:Female; D006225:Hand / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D053609:Lethargy / Q000150:complications / Q000401:mortality / Q000473:pathology*; D008124:Locomotion / Q000502:physiology; D008297:Male; D010300:Parkinson Disease / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D012189:Retrospective Studies; D013378:Substantia Nigra / Q000473:pathology*