key: cord-0917499-258hysrf
authors: Giordano, Antonino; Schwarz, Ghil; Cacciaguerra, Laura; Esposito, Federica; Filippi, Massimo
title: COVID-19: can we learn from encephalitis lethargica?
date: 2020-06-17
journal: Lancet Neurol
DOI: 10.1016/s1474-4422(20)30189-7
sha: a8e94b656562a02f5b755bd0af0fff37ba1ae7e4
doc_id: 917499
cord_uid: 258hysrf

nan

In 1918, influenza caused one of the most severe pandemics in history. Encephalitis lethargica emerged at around the same time and affected more than one million individuals. It had a nonspecific prodromal phase, with influenza-like symptoms, and an acute phase, characterised by fever, sleepiness, ocular motility disturbances, and movement disorders. Months to years later, patients experienced subtle chronic neurological manifestations, mainly postencephalitic parkinsonism. 1 Whether 1918 influenza caused encephalitis lethargica is unclear. Von Economo, who first described encephalitis lethargica, proposed a viral cause, and spreading through nasal membranes. 1 Damage of the upper midbrain and substantia nigra has been reported in encephalitis lethargica, and brain atrophy and neurofibrillary tangles have been reported in postencephalitic parkinsonisms, suggesting a shared neurodegenerative component. 1 Up to 85% of patients with SARS-CoV-2 have minor neurological symptoms such as anosmia. 2 Translational models suggest coronaviruses can be neuroinvasive, with an olfactory route into the CNS, 3 transport along axons, 3 and neuron-to-neuron pro pagation towards the brainstem. 4 Such transmission would fit with Von Economo's hypothesis and is reminiscent of spreading via neural connections in neurodegenerative conditions. 5 

Encephalitis lethargica: 100 years after the epidemic

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study

The olfactory bulb: an immunosensory effector organ during neurotropic viral infections

Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43

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We should take advantage of both historical and novel evidence. The prevalence of anosmia, combined with the neuroinvasive properties of coronaviruses, might support neuroinvasion by SARS-CoV-2. Whether the infection might trigger neurodegeneration, starting in the olfactory bulb, in predisposed patients is unknown. We should not underestimate the potential long-term neurological sequelae of this novel coronavirus.