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

  • George D. Vavougios, Neurology Resident, Postdoctoral Research Fellow, Department of Neurology, Athens Naval Hospital
Submitted May 03, 2020

In their study, Gutiérrez-Ortiz et al.1 presented the first cases of COVID-19-associated Miller Fisher syndrome (MFS). The authors provided a concise clinical definition of MFS in their patient, along with ganglioside serology, which was positive for anti-GD1b immunoglobulin G (IgG). Based on the recent discovery of SARS-CoV-2 interaction with host cell gangliosides, Gutiérrez-Ortiz et al’s care report may not only provide insight into the “NeuroCovid-19” spectrum but to MFS’s pathophysiology as well.

Specifically, SARS-CoV-2’s spike protein has been shown to interact with the sialic acids linked to the host’s gangliosides—effectively employing them as attachment factors—prior to its association with the ACE-2 receptor.2 The olfactory nerves—a site of primary if not self-limiting viral inoculation in the setting of COVID-193—express gangliosides—including GD1b— in abundance.4 Based on our knowledge of previous neurotropic coronaviruses, the interaction between host proteases and SARS-CoV-2 furin-like-cleavage spike on the S protein determines subsequent entry, as well as whether neuroinflammation is indolent or fulminant.5 Indolent, self-limiting neuroinvasion—further supported by the lack of SARS-CoV-2 RNA detection—could manifest as self-limiting anosmia, whereas the ganglioside-virus interaction would offer a prominent target for an antiganglioside antibody response.

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. Fantini J, Scala CD, Chahinian H, Yahi N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob Agents 2020:105960.
  3. Vavougios GD. Potentially irreversible olfactory and gustatory impairments in COVID-19: indolent vs. fulminant SARS-CoV-2 neuroinfection. Brain Behav Immun 2020;S0889-1591:30674-30677.
  4. Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Ganglioside composition of the human cranial nerves, with special reference to pathophysiology of Miller Fisher syndrome. Brain Res 1997;745:32–36.
  5. Vavougios GD. Host proteases as determinants of Coronaviral neurotropism and virulence. Brain Behav Immun 2020;S0889-1591:30464–30465.

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