The 1918 Influenza Pandemic: Back to the Future?

<b><i>Background:</i></b> It is just over a century since the 1918 flu pandemic, sometimes referred to as the “mother” of pandemics. This brief retrospective of the 1918 pandemic is taken from the viewpoint of the current SARS-CoV-2/COVID-19 pandemic and is based on a short lecture given during the 2021 Virtual Congress of the ERA-EDTA. <b><i>Summary:</i></b> This review summarizes and highlights some of the earlier pandemic’s salient features, some parallels with today, and some potential learnings, bearing in mind that the flu pandemic occurred over 100 years ago at a time of major turmoil during the climax to WWl, and with limited medical expertise and knowledge, research facilities, or well-structured and resourced healthcare services. While there is little or no information on renal complications at the time, or an effective treatment, some observations in relation to COVID-19 and vaccination are included. <b><i>Key Messages:</i></b> Lessons are difficult to draw from 1918 other than the importance and value of non-pharmaceutical measures to limit viral transmission. While the economic impact of the 1918 pandemic was significant, as it is now with COVID-19, subsequent economic analysis has shown that protecting public health and preserving economic activity are not mutually exclusive. Both H1N1 and SARS-CoV-2 viruses are neurotropic and may cause chronically debilitating neurological diseases, including conditions such as encephalitis lethargica (still debated) and myalgic encephalomyelitis (chronic fatigue syndrome), respectively. Although coronavirus and influenza viral infections have some similarities, they are certainly not the same, as we are realising, and future infectious pandemics may still surprise us, but being “forewarned is forearmed.”

Epidemic hiccups. Aronovich, Vereshchagin (Kozlov) (Vrach. Gaz., 1923 No. 3-4)

Observing the recent cases of hiccups in Petrograd, Aronovich, based on the clinical course of this disease, the only symptom of which is extremely distressing hiccups, appearing quite suddenly in healthy people, sometimes at night, not treatable and just as suddenly disappearing in 3-4 days, believes that these cases can be attributed to the epidemic of encephalitis lethargica.

No Metagenomic Evidence of Causative Viral Pathogens in Postencephalitic Parkinsonism Following Encephalitis Lethargica

Postencephalitic parkinsonism (PEP) is a disease of unknown etiology and pathophysiology following encephalitis lethargica (EL), an acute-onset polioencephalitis of cryptic cause in the 1920s. PEP is a tauopathy with multisystem neuronal loss and gliosis, clinically characterized by bradykinesia, rigidity, rest tremor, and oculogyric crises. Though a viral cause of EL is likely, past polymerase chain reaction-based investigations in the etiology of both PEP and EL were negative. PEP might be caused directly by an unknown viral pathogen or the consequence of a post-infectious immunopathology. The development of metagenomic next-generation sequencing in conjunction with bioinformatic techniques has generated a broad-range tool for the detection of unknown pathogens in the recent past. Retrospective identification and characterization of pathogens responsible for past infectious diseases can be successfully performed with formalin-fixed paraffin-embedded (FFPE) tissue samples. In this study, we analyzed 24 FFPE brain samples from six patients with PEP by unbiased metagenomic next-generation sequencing. Our results show that no evidence for the presence of a specific or putative (novel) viral pathogen was found, suggesting a likely post-infectious immune-mediated etiology of PEP.

“You Are Older, although You Do Not Know That”: Time, Consciousness, and Memory in “A Kind of Alaska” by Harold Pinter (1930–2008)

<i>“A Kind of Alaska”</i> is a one-act play by the British playwright and Nobel Prize winner Harold Pinter (1930–2008), based on the book <i>Awakenings</i> by the neurologist Oliver Sacks (1933–2015). This play, first performed in 1982, is centered around the character of Deborah, a middle-aged woman, struck by <i>encephalitis lethargica</i> (“sleeping sickness”) at the age of 16, who wakes up after 29 years of apparent sleep following the injection of an unnamed drug. This article analyzes how Pinter’s drama investigated the mysterious and fascinating relationship between time, memory, and consciousness. The term “awakenings,” chosen by Sacks himself, clearly refers to the restoration of voluntary motor function in patients with postencephalitic parkinsonism who responded to levodopa. However, it also suggests that these patients had an impairment of awareness. Actually, beyond the acute phase, subjects with postencephalitic parkinsonism were not sleeping but severely akinetic and therefore probably aware of the passage of time. Oliver Sacks probably did not entirely recognize the intrinsic contradiction between prolonged sleep (with consequent impairment of awareness and subjective “time gap”) of the acute lethargic phase and the severe akinesia with preserved awareness of the time-passing characteristic of postencephalitic parkinsonism. This confusion was further compounded by Harold Pinter in his play.

Tics in patients with encephalitis

Background Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies. Objective This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis. Methods We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-d-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed. Discussion The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.