Miller Fisher syndrome and polyneuritis cranialis in COVID-19
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- COVID-19 Clinical Manifestation Including Long COVID, Encyclopedia of Forensic and Legal Medicine, (791-797), (2025).https://doi.org/10.1016/B978-0-443-21441-7.00267-3
- Bilateral Sequential Abducens Nerve Palsy After Pfizer-BioNTech COVID-19 Vaccine (BNT162b2): A Case Report and Literature Review, Cureus, (2024).https://doi.org/10.7759/cureus.51682
- Perspective Chapter: Respiratory Disorders and Brain Damage in Long COVID, Current Topics in Post-COVID Syndromes [Working Title], (2024).https://doi.org/10.5772/intechopen.1006968
- Posterior Segment Ocular Findings in Critically Ill Patients with COVID, New COVID-19 Variants - Diagnosis and Management in the Post-Pandemic Era, (2024).https://doi.org/10.5772/intechopen.1004050
- Meningoencefalitis asociada a Parálisis del III Nervio Craneal por SARS-CoV-2: Reporte de un caso, Revista Mexicana de Oftalmología, 97, 5S, (130-133), (2024).https://doi.org/10.5005/rmo-11013-0064
- Meningoencephalitis associated with Third Cranial Nerve Palsy by SARS-CoV-2: Report of a Case, Revista Mexicana de Oftalmología, 97, 5E, (130-133), (2024).https://doi.org/10.5005/rmo-11013-0063
- COVID-19 AS A TRIGGER FOR THE ONSET AND PROGRESSION OF NEURODEGENERATIVE PATHOLOGY PREDOMINANTLY IN ELDERLY AND SENILE POPULATION, Успехи геронтологии, 36, 6, (810-817), (2024).https://doi.org/10.34922/AE.2023.36.6.006
- The involvement of the dysfunctional insulin receptor signaling system in long COVID patients with diabetes and chronic pain and its implications for the clinical management using taVNS, Frontiers in Pain Research, 5, (2024).https://doi.org/10.3389/fpain.2024.1486851
- Identification of key genes as potential diagnostic and therapeutic targets for comorbidity of myasthenia gravis and COVID-19, Frontiers in Neurology, 14, (2024).https://doi.org/10.3389/fneur.2023.1334131
- Case report: Rare Guillain-Barré syndrome variants and mild encephalitis/encephalopathy with a reversible splenial lesion as the para-infectious manifestations of SARS-CoV-2 infection, Frontiers in Immunology, 15, (2024).https://doi.org/10.3389/fimmu.2024.1458231
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We thank Drs. Ni and Xu for their letter on our study.1 We think that our two patients developed Miller Fisher syndrome and polyneuritis cranialis due to an aberrant immunologic response to COVID-19. As we previously commented in the article, oropharyngeal swab test for SARS-CoV-2 by qualitative real-time reverse-transcriptase–polymerase-chain-reaction (PCR) assay was positive in both patients and negative in the cerebrospinal fluid (CSF). We did not examine the presence of antibodies for SARS-CoV-2 in CSF because that technique had not been validated. In the patient who acutely presented with Miller Fisher syndrome, CSF PCR for enterovirus, herpes simplex virus type 1 and 2, and varicella zoster virus were negative as well as CSF-VDRL test. On the other hand, in the patient with polyneuritis cranialis, these tests could not performed because of the extreme circumstances of the University Hospital “Príncipe de Asturias”, Alcala de Henares, Madrid, at the peak of this pandemic. Notwithstanding, considering the temporal relationship, we feel that SARS-CoV-2 infection was responsible for the development of these two neurological pictures.
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The authors report no relevant disclosures. Contact [email protected] for full disclosures.
Reference
We read with great interest the case reports about COVID-19 patients with Miller Fisher Syndrome and polyneuritis cranialis by Gutiérrez-Ortiz et al,1 which provided a link between these diseases and the symptom spectrum of SARS-CoV-2 infection. As we know, Miller Fisher Syndrome and polyneuritis cranialis are an autoimmune neuropathy triggered by autoantibodies specific for the polysialogangliosides GQ1b and GT1a in axonal terminals and causes the inflammation and demyelination of the peripheral and cranial nerves.2 A recent article also proposed that autoimmune injury may be involved in the mechanisms of nervous system symptoms of COVID-19.3 In addition, Zika virus—another coronavirus—is also associated with autoimmune peripheral neuropathy.4,5 These thus support the connection of Miller Fisher Syndrome and polyneuritis cranialis with SARS-CoV-2 infection. We wonder whether the authors examined the presence of SARS-CoV-2 RNA and antibodies for SARS-CoV-2 in cerebrospinal fluid (CSF) and ruled out the infection by other common viruses in two COVID-19 patients? This will provide more convincing evidence to support SARS-CoV-2 infection-induced autoimmune injury on peripheral nerves and immunoglobulin therapy may be considered for some COVID-19 patients.
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The authors report no relevant disclosures. Contact [email protected] for full disclosures.
References
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, PhD1, 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
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
We read with interest the report by Gutiérrez-Ortiz et al.1 Starting from the analysis of two cases of Miller Fisher Syndrome and cranial polyneuritis, the authors propose some hypotheses regarding the pathogenesis of neurologic manifestations during COVID-19. They affirm that there may be a common pathogenesis among all neurologic clinical features of COVID-19, including chemosensitive disorders, which appear frequently in these patients in Europe.
In recent weeks, we have gained a great deal of experience with these types of dysfunctions, which appear to affect more than 70% of COVID-19 cases.2,3 Based on the clinical evaluation of these patients, we also asked ourselves what the pathogenesis of these disorders could be.4 Anosmia and ageusia during COVID-19 generally regress within 1–2 weeks. Moreover, their frequency seems to be much higher than any manifestation linked to a central nervous system involvement. For these reasons, neurologic manifestations are more likely to be linked to inflammatory phenomena than to invasion of the central nervous system with neuronal damage. Specifically, as regards anosmia, the target of the virus could be represented by non-neuronal supporting cells of the olfactory epithelium and pathway, which negatively influence the activity of olfactory neurons through inflammatory mechanisms.5
The alteration of the gustatory function—which has a greater tendency to resolve than olfaction—could instead be altered by the direct action of the virus on the ACE-2 receptors of the taste buds. Besides, ageusia is a well-known side effect of ACE-2 inhibitors.
Disclosure
The authors report no relevant disclosures. Contact [email protected] for full disclosures.
References