Influenza RNA not detected in archival brain tissues from acute encephalitis lethargica cases or in postencephalitic Parkinson cases

Encephalitis lethargica (EL) was a mysterious epidemic, temporally associat ed with the 1918 Spanish influenza pandemic. Numerous symptoms characterize d this disease, including headache, diplopia, fever, fatal coma, delirium, oculogyric crisis, lethargy, catatonia, and psychiatric symptoms. Many pati ents who initially recovered subsequently developed profound, chronic parki nsonism. The etiologic association of influenza with EL is controversial. F ive acute EL autopsies and more than 70 postencephalitic parkinsonian autop sies were available in the Armed Forces Institute of Pathology (AFIP) tissu e repository. Two of these 5 acute EL cases had histopathologic changes con sistent with that diagnosis. The remaining 3 cases were classified as possi ble acute EL cases as the autopsy material was insufficient for detailed hi stopathologic examination. RNA lysates were prepared from 29 CNS autopsy ti ssue blocks from the 5 acute cases and 9 lysates from blocks containing sub stantia nigra from 2 postencephalitic cases. RNA recovery was assessed by a mplification of beta-2-microglobulin mRNA and 65% of the tissue blocks cont ained amplifiable RNA. Reverse transcription-polymerase chain reaction (RT- PCR) for influenza matrix and nucleoprotein genes was negative in all cases . Thus, it is unlikely that the 1918 influenza virus was neurotropic and di rectly responsible for the outbreak of EL.