title: Encephalitis of unclear origin diagnosed by brain biopsy: a diagnostic challenge.
abstract: OBJECTIVE
  Brain biopsy specimens that exhibit encephalitis without specific histopathologic features pose a diagnostic challenge to neuropathologists and neurologists. Such cases are generally referred to pathologically as encephalitis, not otherwise specified (ENOS). A systematic approach to diagnostic evaluation in such patients is challenging, and currently there is no generally accepted algorithm.
  
  
  OBJECTIVE
  To examine ultimate diagnostic outcomes in patients with ENOS diagnosed by brain biopsy.
  
  
  METHODS
  This retrospective case series at the University of California, San Francisco, Medical Center, a tertiary care urban neurosciences center, studied patients with encephalitis diagnosed by brain biopsy from January 1, 1983, through December 31, 2011.
  
  
  METHODS
  Brain biopsy.
  
  
  METHODS
  Clinical and neuropathologic diagnosis.
  
  
  RESULTS
  Among 58 patients who met the inclusion criteria for the study, the original pathologic diagnosis was ENOS in 49 patients (84%). The median age was 40 years (interquartile range, 27-53 years), 35 patients were male, and 13 had known human immunodeficiency virus or AIDS. Median time from onset of symptoms to brain biopsy was 66 days (interquartile range, 18-135 days). For the 29 patients in whom material for pathologic analysis was still available, additional neuropathologic review led to a more specific categorization in 10 (34%). Clinical detail and follow-up information was available for 42 patients, and a specific diagnosis was reached with the help of ancillary testing and/or clinical follow-up in 12 patients. Despite a comprehensive neuropathologic review with additional studies and information, 27 patients still had to be classified in the ENOS category at the end of the study.
  
  
  CONCLUSIONS
  ENOS is the most common initial type of encephalitis diagnosed by brain biopsy. In such patients, it may be worth having the biopsy materials reviewed again in a comprehensive fashion by a neuropathologist because additional review led to a more specific categorization in one-third of our cases. Ancillary testing, clinical correlation, and clinical follow-up establish more specific diagnoses in some patients. ENOS still remains a diagnostic challenge after all these efforts in many cases. Current algorithms are of limited value. More advanced methods and better diagnostic algorithms are needed to characterize these patients.
authors.affiliation: Multiple Sclerosis and Neuroinflammation Center, Department of Neurology, University of California, San Francisco.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gelfand
authors.affiliation: Department of Pathology, University of California, San Francisco.
authors.forename: Gillian
authors.initials: G
authors.lastname: Genrich
authors.affiliation: Multiple Sclerosis and Neuroinflammation Center, Department of Neurology, University of California, San Francisco.
authors.forename: Ari J
authors.initials: AJ
authors.lastname: Green
authors.affiliation: Department of Pathology, University of California, San Francisco.
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.affiliation: Multiple Sclerosis and Neuroinflammation Center, Department of Neurology, University of California, San Francisco.
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
mesh_terms: D000328:Adult; D000465:Algorithms; D001706:Biopsy / Q000379:methods*; D001921:Brain / Q000473:pathology*; D016009:Chi-Square Distribution; D004660:Encephalitis / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies