Encephalitis lethargica (EL) was a mysterious epidemic. temporally associated with the 1918 Spanish influenza pandemic. Numerous symptoms characterized this disease, including headache, diplopia, fever, fatal coma, delirium, oculogyric crisis, lethargy, catatonia, and psychiatric symptoms. Many patients who initially recovered subsequently developed profound, chronic parkinsonism. The etiologic association of influenza with EL is controversial. Five acute EL autopsies and more than 70 postencephalitic parkinsonian autopsies were available in the Armed Forces Institute of Pathology (AFIP) tissue repository. Two of these 5 acute EL cases had histopathologic changes consistent with that diagnosis. The remaining 3 cases were classified as possible acute EL cases as the autopsy material was insufficient for detailed histopathologic examination. RNA lysates were prepared from 29 CNS autopsy tissue blocks from the 5 acute cases and 9 lysates from blocks containing substantia nigra from 2 postencephalitic cases. RNA recovery was assessed by amplification of beta-2-microglobulin mRNA and 65% of the tissue blocks contained 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 directly responsible for the outbreak of EL.

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

Movement disorder emergencies in childhood

Parkinson's disease is not one disease.

The current pandemic of coronavirus disease 2019 (COVID-19) has gained increased attention in the neuroscience community, especially taking into account the neuroinvasive potential of its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of its infection on the structure and function of the brain. Apart from the neurotropic properties of SARS-CoV-2, it is likewise important the observation that virus infection may perturb specific cellular processes that are believed to play an important role in the pathogenesis of diverse neurological disorders, particularly in Parkinson's disease (PD). In this scenario, viral infection-induced colon inflammation, gut microbial imbalance, and α-synuclein upregulation are of particular interest with regard to the interplay between the gastrointestinal tract and the central nervous system (microbiome-gut-brain axis). In this Perspective, we present a critical view on the different hypotheses that are recently being raised by neuroscientists about the relationship between SARS-CoV-2 infection and long-lasting neurodegenerative disorders, opening the question of whether COVID-19 might represent a risk factor for the development of PD.

Viral Infection-Induced Gut Dysbiosis, Neuroinflammation, and α-Synuclein Aggregation: Updates and Perspectives on COVID-19 and Neurodegenerative Disorders

The accuracy of the clinical diagnosis of postencephalitic parkinsonism (PEP) is unknown. We determined the validity of the clinical diagnosis of PEP by presenting 105 records with neuropathologic diagnoses of PEP (n = 7), progressive supranuclear palsy (n = 24), Parkinson's disease (n = 15), dementia with Lewy bodies (n = 14), multiple system atrophy (n = 16), corticobasal degeneration (n = 10), Creutzfeldt-Jakob disease (n = 4), and other dementia disorders (n = 15), as clinical vignettes to six neurologists unaware of the autopsy findings. The neurologists' own clinical diagnoses were compared with neuropathologic diagnoses for measures of diagnostic accuracy, including reliability (kappa statistics), sensitivity and positive predictive values for the first and last visits. The group reliability for the diagnosis of PEP was almost perfect (kappa = 0.91, 0.9). The mean sensitivity at the first visit was 86% (range, 71-100%) with minimal change at the last visit (83%; range, 71-100%). Positive predictive values remained unchanged (100%). The high reliability, sensitivity and positive predictive values of the clinical diagnosis of PEP indicate that neurologists identify this disorder even when they report that they have never evaluated a case. In our data set, the best predictors for the diagnosis of PEP included onset below middle age; symptom duration lasting more than 10 years, and the presence of oculogyric crisis. History of encephalitis lethargica, present in most PEP cases, was an important individual diagnostic predictor. Copyright 1998 Lippincott Williams & Wilkins

Barden H

Papers

Influenza A virus as a possible cause of postencephalitic Parkinsonism.