title: West Nile virus neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes.
abstract: BACKGROUND
  West Nile Virus (WNV) is a mosquito-borne flavivirus that has caused ongoing seasonal epidemics in the United States since 1999. It is estimated that ≤1% of WNV-infected patients will develop neuroinvasive disease (West Nile encephalitis and/or myelitis) that can result in debilitating morbidities and long-term sequelae. It is essential to collect longitudinal information about the recovery process and to characterize predicative factors that may assist in therapeutic decision-making in the future.
  
  
  METHODS
  We report a longitudinal study of the neurological outcomes (as measured by neurological examination, Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7, at discharge, and on days 14, 30, and 90. The neurological outcome measures were coma (presence and degree), global cognitive status, presence of cranial neuropathy, tremors and/or weakness.
  
  
  RESULTS
  At initial clinical presentation 93% presented with a significant neurological deficit (49% with weakness, 35% with tremor, and 16% with cranial neuropathy). The number of patients with a cognitive deficit fell from 25 at initial evaluation to 9 at their last evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients at study conclusion. Of the 19 patients who had a tremor at enrollment, 11 continued to exhibit a tremor at follow-up. Seven patients died after initial enrollment in the study, with 5 of those having presented in a coma. The factors that predict either severity or long-term recovery of neurological function include age (older individuals were weaker at follow-up examination), gender (males recovered better from coma), and presentation in a coma with cranial nerve deficits (had a poorer recovery particularly with regard to cognition).
  
  
  CONCLUSIONS
  This study represents one of the largest clinical investigations providing prospectively-acquired neurological outcomes data among American patients with WNV central nervous system disease. The findings show that the factors that influence prognosis from the initial presentation include age, gender, and specific neurological deficits at onset.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00138463 and NCT00069316.
authors.affiliation: Center for BrainHealth, University of Texas at Dallas, Dallas, TX, USA. jhart@utdallas.edu.
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.forename: Gail
authors.initials: G
authors.lastname: Tillman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kraut
authors.forename: Hsueh-Sheng
authors.initials: HS
authors.lastname: Chiang
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Strain
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.forename: Amy G
authors.initials: AG
authors.lastname: Agrawal
authors.forename: Penny
authors.initials: P
authors.lastname: Jester
authors.forename: John W
authors.initials: JW
authors.lastname: Gnann
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitley
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000401:mortality / Q000821:virology*; D011379:Prognosis; D011446:Prospective Studies; D012044:Regression Analysis; D014481:United States / Q000453:epidemiology; D014901:West Nile Fever / Q000150:complications* / Q000401:mortality; D014902:West Nile virus