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Comment & Response
June 2015

Diagnosing Encephalitis, Not Otherwise Specified—Reply

Author Affiliations
  • 1Department of Neurology, University of California, San Francisco
  • 2Multiple Sclerosis Center, University of California, San Francisco
JAMA Neurol. 2015;72(6):726-727. doi:10.1001/jamaneurol.2015.0548

In Reply We agree with Wang and colleagues that clinical-pathological correlation is important in diagnosing the cause of encephalitis. It is possible that with contemporary technology more of these cases might have been confirmed as autoimmune or paraneoplastic based on advances in cerebrospinal fluid (CSF) or serum detection of antineuronal antibodies (banked CSF or serum was not available). Unbiased sequencing techniques pioneered at our institution using CSF and biopsy material are also beginning to provide significant and actionable findings.1 However, even today, there are many cases of encephalitis wherein the final diagnosis remains elusive despite extensive commercial- and research-grade testing for infectious, paraneoplastic, and autoimmune causes. There are also still cases of encephalitis, not otherwise specified (ENOS) that become apparent on brain biopsy when the preoperative diagnosis was not necessarily encephalitis. Completion of the pathology report and assessment of pathological findings are hardly ever performed without clinical and radiological correlation, and it is the rule rather than the exception that in these enigmatic cases, there is extensive discussion between the pathologist and clinical team to better understand the findings. Our results indicate that when the initial pathological diagnosis is ENOS, re-review of the pathological material, clinical reevaluation, and focused laboratory testing can have added diagnostic value.2

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