key: cord-1042334-dhdg6n05
authors: Toljan, Karlo; Amin, Moein; Kunchok, Amy; Ontaneda, Daniel
title: New diagnosis of multiple sclerosis in the setting of mRNA COVID-19 vaccine exposure
date: 2021-12-09
journal: J Neuroimmunol
DOI: 10.1016/j.jneuroim.2021.577785
sha: 47766c34e078d23f69366c0b4e24abc50721406d
doc_id: 1042334
cord_uid: dhdg6n05

BACKGROUND: Multiple sclerosis (MS) with onset in the setting of acute SARS-CoV-2 virus infection has been reported, and reactivation of MS following non-mRNA COVID-19 vaccination has been noted, but there have only been three reports of newly diagnosed MS following exposure to mRNA COVID-19 vaccine. The association cannot be determined to be causal, as latent central nervous system demyelinating disease may unmask itself in the setting of an infection or a systemic inflammatory response. We report a series of 5 cases of newly diagnosed MS following recent exposure to mRNA COVID-19 vaccines. Latency from vaccination to initial presentation varied. Neurological manifestations and clinical course appeared to be typical for MS including response to high dose steroids in 4 cases and additional need for plasmapheresis in one case. CONCLUSION: Acute neurological deficits in the setting of recent mRNA COVID-19 vaccine administration may represent new onset multiple sclerosis.

Multiple sclerosis (MS) with onset in the setting of acute SARS-CoV-2 virus infection has been described. 1-3 Cases of MS reactivation following non-mRNA COVID-19 vaccinations have been reported, 4, 5 but so far only four reports of MS onset following vaccination with the mRNA COVID-19 vaccine have been published. [5] [6] [7] Here, we report five cases of onset of MS in the setting of recent mRNA COVID-19 vaccine administration.

A case series of patients with new onset neurological symptoms in the setting of COVID-19 mRNA vaccine exposure and who were ultimately diagnosed with MS at our tertiary center. Cerebrospinal fluid (CSF) was sampled and showed pleocytosis (8 leukocytes/L), an elevated IgG index (0.71), and 10 oligoclonal unmatched bands in the CSF. Intravenous methylprednisolone (1g/day) was given for five days with significant improvement in neurological symptoms. Following negative diagnostics for systemic autoimmune conditions with serum testing, MS was diagnosed and ocrelizumab was started five weeks after initial presentation.

A 37-year-old male without significant medical history developed left hand paresthesia three days following the first dose of Pfizer-BioNTech COVID-19 vaccine. By the time he got the second dose, three weeks later, paresthesia spread over the entire left arm. Three months following initial symptom onset he developed urinary urgency and gait imbalance. Exam was notable for right sided internuclear ophthalmoplegia and isolated left arm hyperreflexia (3+).

MRI scans of the brain and cervical spine were obtained. There were multiple periventricular non-enhancing T2/FLAIR hyperintensities and a C3-C4 cord T2 and STIR hyperintense lesion, compatible with demyelination ( Figure 1 .c-e). Patient completed a high dose oral prednisone taper over 12 days following 3 days of 600 mg oral prednisone. A diagnosis of MS was established following negative serum diagnostics for mimics. Serum aquaporin 4-IgG (AQP4-IgG) and myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) cell based assays (CBAs) were negative. Further decision regarding disease-modifying therapy is pending. Treatment with rituximab-pvvr was started.

The factors governing onset of MS is an area of active research, with still many unresolved questions, though it appears that MS is a multifactorial disease which may present when specific environmental triggers occur in a susceptible individual. 8 Besides certain genetic susceptibilities, some environmental factors, including infections, such as the Epstein-Barr virus, have been postulated as a pre-requisite step in the etiological cascade ultimately leading to MS. 9 The role of viruses, including coronaviruses, in the pathogenesis of MS is unclear, 10 Alternatively the occurrence of these cases may represent a spurious association given a combination of a common event, namely vaccination with mRNA COVID-19 vaccines (currently at 56.2% of the Ohio population as reported on www.coronavirus.ohio.gov), and MS as a neurological disease with relatively common incidence. We have not seen a major increase in MS cases referred to our center since the implementation of COVID-19 vaccination, but further epidemiological studies are needed to substantiate this observation. This association warrants further systematic investigation, as COVID-19 vaccination, and in our cases mRNA vaccination, appears to be associated with inflammatory MS disease activity. In real-world safety J o u r n a l P r e -p r o o f reports based on MS, MOG antibody disease, neuromyelitis optica spectrum disorder, and transverse myelitis populations (963 patients), exposure to Pfizer-BioNTech COVID-19 vaccine has been associated with new or worsening neurological symptoms in less than ~15% of patients, commonly occurring early in the post-vaccination period (<7 days), and mostly self-resolving within 2 weeks, 18, 19 Although there is evidence of immune activation with vaccines leading to other neuroimmunological disorders such as Guillain-Barré Syndrome, acute disseminated encephalomyelitis, or transverse myelitis, this has not been the case for MS. 20,21 Despite broad use of mRNA COVID-19 vaccines, there have been few reports of MS flares in the short-term post-vaccination period as well as optic neuritis and transverse myelitis. 22 ,23 A cohort of 555 MS patients receiving at least one dose of Pfizer-BioNTech mRNA COVID-19 vaccine did not experience an increase in relapse rate as compared to the unvaccinated population. 24 In our cases the decision of whether to recommend future or subsequent mRNA COVID-19 vaccination presents a potential clinical challenge. Of note, completion of vaccination with the second dose was recommended in the fourth presented case. In other autoimmune inflammatory conditions which developed shortly after vaccination, such as Guillain-Barré Syndrome, avoiding the same vaccination in the future has been suggested. 25 

We present a series of 5 patients with de novo MS diagnoses following recent mRNA COVID-19 vaccination. The causality of vaccination and onset of MS cannot be determined. 12/7/2021 10:56:00 AM Based on these cases we cannot conclude whether vaccination represents a trigger in an otherwise predisposed or pre-symptomatic MS phase versus a purely spurious result as a consequence of vaccination in a very large proportion of the population, where incident cases occur independent of vaccination. Further systematic research is needed to clarify a possible J o u r n a l P r e -p r o o f underlying association between mRNA COVID-19 vaccination and the onset of MS. The overall benefits of COVID-19 vaccination, however cannot be understated, and although these cases represent interesting findings they remain relatively rare occurrences and should not dissuade vaccine use in the general population or even in the MS population.

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Figure 1. Neuroimaging findings in five reported cases diagnosed as multiple sclerosis (MS)

In case 3, prominent T2/FLAIR hyperintensities (f) with contrast enhancement (g) are seen on axial projection, with additional multifocal short-tau inversion recovery (STIR) hyperintensities on sagittal image (h), which was supportive of active MS. In case 4, a sagittal T2/FLAIR sequence projection demonstrates typical MS lesions (i) with associated contrast enhancement (not shown) and accompanying spinal cord lesions seen on T2-weighted sequence (j)

Authors thank Dr Megan Nakashima and Dr Edmunds Reineks for their assistance in particular data acquisition while preparing the manuscript.