New series on Neuro-COVID - Epilepsy, Myasthenia Gravis and Multiple Sclerosis

Introduction by Prof. Avindra Nath and Dr Jeanne Billioux, Tropical and Geographical Neurology Specialty Group

We are starting a new series on Neuro-COVID. We will review the most pertinent literature published over the past month to discuss a specific topics of interest regarding COVID-19 and Neurology.

Over the past month, several articles were published on COVID-19 vaccines in specific neurologic disease populations, including recommendations, side effects and tolerability, and considerations.

Epilepsy

Per the International League against Epilepsy and other organizations, it is recommended that patients with epilepsy get vaccinated against COVID-19, and there is no evidence of contraindications for patients with epilepsy for the COVID-19 vaccines (www.ilae.org/.../covid-19-vaccines-and-people-with-epilepsy ⧉).   To echo these concerns, a recent article published in Journal of Neurological Sciences looked at a cohort of Turkish people with epilepsy who were recently vaccinated, and determined that there was no significant change in the number of monthly seizures in this cohort before vaccine (1.62), in between doses (1.61), or after final dosing of the vaccination (1.64, p=0.46) (Özdemir 2022 10.1007/s10072-022-05956-6).

Myasthenia Gravis

It is recommended that patients with Myasthenia Gravis get vaccinated against COVID-19 (https://doi.org/10.1016/j.jns.2020.116803 ⧉) including an additional dose if they are on immunosuppressive agents (www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html ⧉) ; however, information on side effects and tolerability of different vaccines has been so far limited in this disease population.

A recent study evaluated the early safety and tolerability of the Pfizer/BioNTech BNT162b2 vaccine in an Israeli cohort of myasthenia gravis patients. Although the study was conducted via survey with a small sample size of 56 participants, the authors found that the vaccine was overall well tolerated in this population, with eight (14.5%) respondents reporting worsening in their neurologic symptoms and only three of these respondents requiring change in management of their illness after vaccination (Lotan 2022 10.1016/j.nmd.2022.01.013 ⧉).

Multiple Sclerosis

Similar to patients with myasthenia gravis, there are many patients with multiple sclerosis on immunomodulating therapies, and details on safety and tolerability in this particular disease population are forthcoming. Currently, it is recommended that patients with multiple sclerosis receive vaccination against COVID-19 (www.nationalmssociety.org/.../multiple-sclerosis-and-coronavirus/covid-19-vaccine-guidance ⧉ ) including an additional dose in patients on immunosuppressive agents.

There has been interest in understanding the impact of disease modifying therapies (DMTs) on vaccination in this population. A recent German study evaluating the humoral and cellular immune responses of multiple sclerosis patients on a variety of DMTs before and after COVID-19 vaccination found that patients on interferon beta treatment produced robust humoral and cellular responses, while patients on ocrelizumab had lower humoral immune responses and patients on natalizumab had lower cellular immune responses compared to controls.  The authors suggest monitoring of both humoral and cellular immune responses in patients on DMTs, and note that these patients may benefit from both additional vaccine doses as well as treatment with SARS-CoV-2 antibodies in case of Covid-19 (Trümpelmann 2022 10.1111/cts.13256 ⧉).

Another group evaluated the IgG responses after a third dose of mRNA Covid-19 vaccine in 8 patients taking fingolimod who had insufficient immune response after the standard vaccine schedule, and found that half of these patients achieved a sufficient humoral immune response after the additional vaccine dose (Achtnichts 2022 10.3390/vaccines10020341 ⧉), which harmonizes with the CDC’s current recommendations for additional vaccine doses for moderately to severely immunocompromised people.

In light of the recent Omicron wave, a study was undertaken in multiple sclerosis patients on ocrelizumab receiving their third dose of an mRNA vaccine, which showed robust T-cell responses against both Delta and Omicron variants, suggesting that vaccine-induced cellular immunity are likely protective against COVID-19 despite B-cell depletion therapy (Madelon 2022 10.1001/jamaneurol.2022.0245 ⧉).

Regarding timing of Covid-19 vaccination in conjunction with various DMTs given in MS patients, the National MS Society provides excellent guidance found here: www.nationalmssociety.org/.../Timing-MS-Medications-with-COVID-19-Vaccines ⧉.

Another consideration in multiple sclerosis patients and other neuroimmunology patients concerns the potential for relapse related to COVID-19 vaccination.  A case report was just published of a woman with MS who had a relapse after receiving her second dose of an mRNA vaccination, and recovered well with a course of methylprednisolone; in reviewing the literature, a number of case reports and case series of MS relapse after Covid-19 vaccination have been reported, although it seems to be an overall uncommon occurrence with protection against COVID-19 outweighing this potential risk of relapse (Kataria 2022 10.7759/cureus.21374 ⧉).

Relapses have also been reported in Neuromyelitis optica spectrum disease (NMOSD) patients after Covid-19 vaccination, although this has not yet been well-characterized. A retrospective multicenter Italian study of 56 NMOSD patients who received SARS-Co-V2 vaccination found that only one patient suffered from a relapse within a month after receiving vaccination.  Although this is a small sample size, this study indicates that the vaccination in NMOSD patients is well-tolerated and that protection against COVID-19 outweighs risk of relapse in these patients who are often under varying degrees immunomodulation (Dinoto 2022 10.1016/j.msard.2021.103424 ⧉).

References

• Özdemir, H.N., Dere, B., Gökçay, F. et al. Are COVID-19 vaccines safe for people with epilepsy? A cross-sectional study. Neurol Sci (2022). https://doi.org/10.1007/s10072-022-05956-6 ⧉
• Lotan I, Hellmann MA, Friedman Y, Stiebel-Kalish H, Steiner I, Wilf-Yarkoni A. Early safety and tolerability profile of the BNT162b2 COVID-19 vaccine in myasthenia gravis. Neuromuscul Disord. 2022 Feb 5:S0960-8966(22)00030-X. doi: 10.1016/j.nmd.2022.01.013 ⧉. Epub ahead of print. PMID: 35227552; PMCID: PMC8817458.
• Trümpelmann S, Schulte-Mecklenbeck A, Steinberg OV, Wirth T, Fobker M, Lohmann L, Lünemann JD, Wiendl H, Gross CC, Klotz L. Impact of disease-modifying therapies on humoral and cellular immune-responses following SARS-CoV-2 vaccination in MS patients. Clin Transl Sci. 2022 Feb 25. doi: 10.1111/cts.13256 ⧉. Epub ahead of print. PMID: 35213793.
• Achtnichts L, Ovchinnikov A, Jakopp B, Oberle M, Nedeltchev K, Fux CA, Sellner J, Findling O. SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot. Vaccines. 2022; 10(2):341. https://doi.org/10.3390/vaccines10020341 ⧉
• Madelon N, Heikkilä N, Sabater Royo I, Fontannaz P, Breville G, Lauper K, Goldstein R, Grifoni A, Sette A, Siegrist CA, Finckh A, Lalive PH, Didierlaurent AM, Eberhardt CS. Omicron-Specific Cytotoxic T-Cell Responses After a Third Dose of mRNA COVID-19 Vaccine Among Patients With Multiple Sclerosis Treated With Ocrelizumab. JAMA Neurol. 2022 Feb 25. doi: 10.1001/jamaneurol.2022.0245 ⧉. Epub ahead of print. PMID: 35212717.
• Kataria S, Rogers S, Bilal U, Baktashi H, Singh R. Multiple Sclerosis Relapse Following COVID-19 Vaccination: A Case Report and Literature Review. Cureus. 2022 Jan 18;14(1):e21374. doi: 10.7759/cureus.21374 ⧉. PMID: 35198286; PMCID: PMC8854205.
• Dinoto A, Sechi E, Ferrari S, Gajofatto A, Orlandi R, Solla P, Maccabeo A, Maniscalco GT, Andreone V, Sartori A, Manganotti P, Rasia S, Capra R, Mancinelli CR, Mariotto S. Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD. Mult Scler Relat Disord. 2022 Feb;58:103424. doi: 10.1016/j.msard.2021.103424 ⧉. Epub 2021 Nov 22. PMID: 35216793; PMCID: PMC8607690.