Influenza caused epidemic encephalitis (encephalitis lethargica): The circumstantial evidence and a challenge to the nonbelievers

Maurizi, C.P.

doi:10.1016/j.mehy.2009.12.012

Cited by 42 publications

(32 citation statements)

References 15 publications

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“…Because natural infections can trigger autoimmune disease through molecular mimicry (5) (for example, Sydenham chorea is the result of an immune response cross-reacting with similar proteins contained in the microbe, b-hemolytic streptococcus, and the human brain), we compared these three microbial sequence fragments from influenza for similarity to fragments contained in human HCRT ligand or the HCRT receptors (components of the neurotransmission pathway dysregulated in narcolepsy) using a Smith-Waterman alignment. From these three fragments, only the sequence of influenza NP 111-121 , "YDKEEIRRIWR," was found to be similar to (mimicked) a sequence from the first extracellular domain (N terminus) of HCRT receptor 2 [34][35][36][37][38][39][40][41][42][43][44][45] , "YDDEEFLRYLWR" (e value = 0.0061), and the corresponding domain of HCRT receptor 1 [27][28][29][30][31][32][33][34][35][36][37] , "YEDEFLRYLWR" (e value = 0.026) (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2

Ahmed

Volkmuth²,

Duca³

et al. 2015

Sci. Transl. Med.

222

195

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The sleep disorder narcolepsy is linked to the HLA-DQB1*0602 haplotype and dysregulation of the hypocretin ligand-hypocretin receptor pathway. Narcolepsy was associated with Pandemrix vaccination (an adjuvanted, influenza pandemic vaccine) and also with infection by influenza virus during the 2009 A(H1N1) influenza pandemic. In contrast, very few cases were reported after Focetria vaccination (a differently manufactured adjuvanted influenza pandemic vaccine). We hypothesized that differences between these vaccines (which are derived from inactivated influenza viral proteins) explain the association of narcolepsy with Pandemrix-vaccinated subjects. A mimic peptide was identified from a surface-exposed region of influenza nucleoprotein A that shared protein residues in common with a fragment of the first extracellular domain of hypocretin receptor 2. A significant proportion of sera from HLA-DQB1*0602 haplotype-positive narcoleptic Finnish patients with a history of Pandemrix vaccination (vaccine-associated narcolepsy) contained antibodies to hypocretin receptor 2 compared to sera from nonnarcoleptic individuals with either 2009 A(H1N1) pandemic influenza infection or history of Focetria vaccination. Antibodies from vaccine-associated narcolepsy sera cross-reacted with both influenza nucleoprotein and hypocretin receptor 2, which was demonstrated by competitive binding using 21-mer peptide (containing the identified nucleoprotein mimic) and 55-mer recombinant peptide (first extracellular domain of hypocretin receptor 2) on cell lines expressing human hypocretin receptor 2. Mass spectrometry indicated that relative to Pandemrix, Focetria contained 72.7% less influenza nucleoprotein. In accord, no durable antibody responses to nucleoprotein were detected in sera from Focetria-vaccinated nonnarcoleptic subjects. Thus, differences in vaccine nucleoprotein content and respective immune response may explain the narcolepsy association with Pandemrix.

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Section: Resultsmentioning

confidence: 99%

Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2

Ahmed

Volkmuth²,

Duca³

et al. 2015

Sci. Transl. Med.

222

195

View full text Add to dashboard Cite

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“…The lethargy lasted from several days to a few months, and frequently culminated in coma and death secondary to respiratory failure [4]. About 80% of the patients who recovered from EL went on to develop a Parkinson’s-like disease [4, 11]. The Parkinsonian features described included tremor, bradykinesia and masked facies [12].…”

Section: Resultsmentioning

confidence: 99%

Parkinsonism and neurological manifestations of influenza throughout the 20th and 21st centuries

Henry

Smeyne

Jang

et al. 2010

Parkinsonism & Related Disorders

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Purpose Given the recent paper by Jang et al. on “A Highly Pathogenic H5N1 Influenza Virus” which reported a novel animal model of parkinsonism, we aimed to perform a complete historical review of the 20th and 21st century literature on parkinsonism and neurological manifestations of influenza. Scope There were at least twelve major flu pandemics reported in the literature in the 20th and 21st century. Neurological manifestations most prevalent during the pandemics included delirium, encephalitis, ocular abnormalities, amyotrophy, myelopathy, radiculopathy, ataxia and seizures. Very little parkinsonism was reported with the exception of the 1917 cases originally described by von Economo. Conclusions To date there have been surprisingly few cases of neurological issues inclusive of parkinsonism associated with influenza pandemics. Given the recent animal model of H5N1 influenza associated parkinsonism, the medical establishment should be prepared to evaluate for the re-emergence of parkinsonism during future outbreaks.

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Section: Discussionmentioning

confidence: 99%

“…Others suggest that the association cannot be ruled out [7, 12, 58]. No gold standard titer testing was available at the time, making diagnosis of EL and influenza subjective and based on clinical findings alone [12, 58]. The supervisor of the vaccine trials for EL and a major contributor to the Matheson commissioned EL literature survey Josephine Neal in 1942 commented “the range of symptomatology in acute EL was so wide that often the diagnosis could be made only with difficulty and occasionally not with certainty” [12].…”

Section: Discussionmentioning

confidence: 99%

The Demise of Poskanzer and Schwab’s Influenza Theory on the Pathogenesis of Parkinson’s Disease

Estupinan

Nathoo

Okun

2013

Parkinson's Disease

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In 1961, David C. Poskanzer and Robert S. Schwab presented a paper, “Studies in the epidemiology of Parkinson's disease predicting its disappearance as a major clinical entity by 1980.” This paper introduced the hypothesis that Parkinson's disease was derived from a single aetiology, the influenza virus. We review the original Poskanzer and Schwab hypothesis that Parkinson's disease was based on the association between the 1918-19 influenza epidemic and the later observation of Parkinsonism in some influenza sufferers. We also further explore the prediction that Parkinson's disease would totally disappear as an entity once original influenza victims were all deceased. Current research has revealed that there are many potential causes and factors important in the occurrence of Parkinson's disease, postencephalitic Parkinsonism, and encephalitis lethargica. Poskanzer and Schwab presented a novel hypothesis; however, it was proven false by a combination of research and time.

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Influenza caused epidemic encephalitis (encephalitis lethargica): The circumstantial evidence and a challenge to the nonbelievers

Cited by 42 publications

References 15 publications

Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2

Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2

Parkinsonism and neurological manifestations of influenza throughout the 20th and 21st centuries

The Demise of Poskanzer and Schwab’s Influenza Theory on the Pathogenesis of Parkinson’s Disease

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