Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccines: A systematic review.

BACKGROUND: The global COVID-19 pandemic began in March 2019, and given the number of casualties and adverse effects on the economy, society, and all aspects of the health system, efforts have been made to develop vaccines from the beginning of the pandemic. Numerous vaccines against COVID-19 infection have been developed in several technologies and have spread rapidly. There have been reported multiple complications of the COVID-19 vaccines as with other vaccines. A number of studies have reported multiple sclerosis (MS ) and neuromyelitis optica spectrum disorder (NMOSD) as complications of COVID-19 vaccines. METHODS: First, we found 954 studies from 4 databases (PubMed, Embase, Scopus, and Web of Science) from inception to March 1st, 2022. Next, duplicate articles were eliminated, and 476 studies remained. Then 412 studies were removed according to inclusion and exclusion criteria. After obtaining the full text of 64 articles, 12 studies were selected finally. RESULTS: The data were extracted from included studies in a table. Our data includes demographic data, comorbidities, vaccines information and side effects, NMOSD and MS symptoms, laboratory and cerebrospinal fluid (CSF) findings, magnetic resonance imaging (MRI) results, treatment, and outcome of all cases. CONCLUSION: MS and NMOSD are two neuroinflammatory disorders that arise in the CNS. Cases of MS and NMOSD have been reported following COVID-19 vaccination. Nevertheless, more studies with more subjects are needed to assess any possible relationship between the COVID-19 vaccine and central nervous system demyelination.

Optic neuromyelitis after vaccination against SARS-CoV-2.

Neuromyelitis optica is an autoimmune demyelinating astrocytopathy of the central nervous system that primarily affects the optic nerve and spinal cord. It is considered a multifactorial disease associated with antibodies against aquaporin 4, with complement cascade activation and lymphocytic infiltration leading to axonal loss and causing significant morbidity and disability. In addition, cases of inflammatory diseases of the central nervous system have been described after vaccination against SARS-CoV-2, mainly acute disseminated encephalomyelitis. Also, a few cases of neuromyelitis optica spectrum disorder, mostly aquaporin 4+, have been reported. We describe a patient who developed symptoms suggestive of acute disseminated encephalomyelitis the next day after vaccination against SARS-CoV-2. Three months later, a longitudinally extensive transverse myelitis compatible with aquaporin 4+ neuromyelitis optica was successfully treated with an interleukin 6 inhibitor. There is no proven association and research is needed to establish whether optic neuromyelitis is related to vaccination; this is a single case report from which no conclusion can be drawn.

Aquaporin-4 IgG neuromyelitis optica spectrum disorder onset after Covid-19 vaccination: Systematic review.

Neuromyelitis optica spectrum disorder (NMOSD) is rarely reported following Coronavirus disease 2019 (COVID-19) vaccination. We identified 16 cases of new onset NMOSD with positive aquaporin-4 IgG (AQP4-IgG) following COVID-19 vaccination. Transverse myelitis was the most common clinical presentation (75%). Most patients received high dose steroids for acute treatment and maintenance therapy was started in 12 patients (75%). Twelve patients (75%) had improvement of their symptoms at the time of discharge or follow-up. The included cases share similar epidemiology and natural course to non-vaccine related cases. Clinicians should be aware of possible post-vaccination NMOSD to help with earlier diagnosis and treatment.

Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report.

BACKGROUND: Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. CASE PRESENTATION: We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer-BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient's symptoms. CONCLUSIONS: Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.

Watch out for neuromyelitis optica spectrum disorder onset or clinical relapse after COVID-19 vaccination: What neurologists need to know?

INTRODUCTION: The ongoing global COVID-19 pandemic has dramatically impacted our lives. We conducted this systematic review to investigate the safety of the COVID-19 vaccines in NMOSD patients. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase from the beginning of the COVID-19 vaccination to March 1, 2022. Except for the letters, posters, and reviews, we included all related articles to answer two main questions. Our first question examined the occurrence of NMOSD onset as an adverse effect of the COVID-19 vaccine. Our second question investigated the safety of the COVID-19 vaccines in NMOSD patients. RESULTS: Out of 262 records, nine studies, including five studies for the first question and four studies for the second question, met the inclusion criteria. Out of the six patients with NMOSD onset after COVID-19 vaccination, five (83.3%) were female. The median time to NMOSD onset was 6.5 days, and the frequency of the COVID-19 vaccine type was identical in all patients. The most common presentation was longitudinally extensive transverse myelitis, significantly improved by pulse methylprednisolone with or without plasma exchange. The maintenance therapy was described only in three patients: rituximab (n=2) and azathioprine (n=1). Regarding the second question, out of 67 patients, 77.61% were female, with a mean age of 54.75 years old, a mean EDSS of 2.83, and a mean disease duration of 9.5 years. 77% reported at least one preexisting comorbidity. 88.05% were under treatment, most of which were rituximab and azathioprine. 98.50% received two doses of the COVID-19 vaccine. mRNA vaccines were the most commonly used vaccine(86.56%), which were well tolerated. No significant adverse event was reported, and local pain was the most frequently reported. 4.67% of the patients experienced a clinical relapse after a mean interval of 49.75 days, which was mainly mild to moderate in severity. Unfortunately, the data on the COVID-19 vaccines were missing. CONCLUSION: The analysis suggests the safety profile of the COVID-19 vaccines. All NMOSD patients are strongly recommended to vaccinate for COVID-19. To maximize the effectiveness of the COVID-19 vaccines, further studies are needed to draw the best practice for vaccination.

COVID-19 associated with encephalomyeloradiculitis and positive anti-aquaporin-4 antibodies: Cause or coincidence?

Neurologic complications are being recognized as important outcomes of coronavirus disease 2019 (COVID-19). Pathogenesis is varied and incompletely understood, and may include neuroinvasion, indirect post-infectious neuroinflammation, and cerebrovascular pathologies. We present a case of COVID-19-related encephalomyeloradiculitis with clinical and magnetic resonance imaging characteristics of neuromyelitis optica spectrum disorders that was associated with anti-aquaporin-4 antibodies. Our case suggests post-infectious autoimmunity as a mechanism in at least a subset of patients with COVID-19-related neurologic disease.

[Treatment of Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder and Myasthenia Gravis during the COVID-19 Pandemic].

Coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become a global pandemic. Neuroimmunological diseases, such as multiple sclerosis, neuromyelitis optica spectrum disorders, and myasthenia gravis, require long-term immunotherapies having the potential to increase the risk of infection. However, there are no evidence-based guidelines for the management of these disease during the pandemic, despite increasing concerns in patients and neurologists. Currently, there is no evidence of an elevated risk of morbidity and aggravation of COVID-19 in patients with these diseases, irrespective of whether they receive treatment. To prevent relapse or aggravation of the underlying diseases due to COVID-19, all patients should perform general preventive measures, such as social distancing, frequent hand washing, and respiratory hygiene. In patients undergoing immunotherapy, current treatment should be continued to prevent exacerbation of symptoms; however, exceptions to this include high-risk patients for COVID-19, such as the elderly, those with comorbidities including cardiac and respiratory diseases, those taking therapy with immunosuppressive agents, and those with deteriorating symptoms of COVID-19.