Author response: Miller Fisher Syndrome and polyneuritis cranialis in COVID-19

We thank Dr. Vavougios and Vaira et al. for their letters on our study,¹ which reported two patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) who acutely presented with Miller Fisher syndrome and polyneuritis cranialis, respectively. We agree with Dr. Vavougios that indolent self-limiting neuroinvasion could manifest as self-limiting anosmia, whereas the ganglioside-virus interaction would offer a prominent target for an antiganglioside antibody response as in our patient with Miller Fisher syndrome. In addition, we also agree with Dr. Vaira et al. regarding anosmia in coronavirus disease 2019 (COVID-19). Indeed, SARS-CoV-2 could negatively influence the activity of olfactory neurons through inflammatory mechanisms. Further study is needed regarding if ageusia could instead be caused by the direct action of the SARS-CoV-2 on the ACE-2 receptors of the taste buds.

However, the exact pathogenesis of COVID-19-induced neurologic manifestations largely remains unknown. Miller Fisher syndrome and polyneuritis cranialis may have occurred because of an aberrant immunologic response to COVID-19. Notwithstanding, we recognize that other neurologic pictures associated with COVID-19 could be caused by alternative mechanisms. Coronaviruses share a similar viral structure, and the pathogenic mechanisms of other coronavirus may also be applicable for SARS-CoV-2.¹ It is known that SARS-COV,² as H1N1 influenza virus,^3,4 when inoculated intranasally, could spread transneuronally to first- and second-order structures connected with the olfactory bulb. SARS-CoV-2 could affect different structures—olfactory bulb and brainstem—sequentially by means of a transneuronal spread and cause specific pictures, such as brainstem myoclonus.⁵

Further investigation is required to clarify the pathogenesis of neurologic manifestations in COVID-19 and its optimal treatment.

Authors: Julián Benito-León, MD, PhD^{1, 2, 3} Antonio Méndez-Guerrero, MD;¹ Consuelo Gutiérrez-Ortiz, MD, PhD;^{4, 5} Sara Rodrigo-Rey, MD;⁴ Eduardo San Pedro-Murillo, MD;¹ Laura Bermejo-Guerrero, MD;¹ Ricardo Gordo-Mañas, MD;⁶

Department of Neurology,¹ University Hospital “12 de Octubre”, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED),² Madrid, Spain; Department of Medicine,³ Universidad Complutense, Madrid, Spain; Department of Glaucoma and Neuro-Ophthalmology,⁴ University Hospital “Príncipe de Asturias”, Alcalá de Henares, Madrid, Spain; Department of Glaucoma,⁵ ”Martínez de Carneros” Clinic, Madrid, Spain; and Department of Neurology,⁶ University Hospital “Príncipe de Asturias”, Alcalá de Henares, Madrid, Spain

References

1. Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology 2020 Epub Apr 17.
2. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 2008;82:7264–7275.
3. de Wit E, Siegers JY, Cronin JM, et al. 1918 H1N1 Influenza Virus Replicates and Induces Proinflammatory Cytokine Responses in Extrarespiratory Tissues of Ferrets. J Infect Dis 2018;217:1237–1246.
4. Tesoriero C, Codita A, Zhang MD, et al. H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice. Proc Natl Acad Sci U S A 2016;113:E368–377.
5. Rábano-Suárez P, Bermejo-Guerrero L, Méndez-Guerrero A. et al. Generalized myoclonus in COVID-19. Neurology 2020 [submitted].