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MRI Brain. a. Hyperintense FLAIR signal white matter lesion in the right frontal lobe (arrow). b Internal punctate enhancement of the right frontal lobe lesion (arrow). c Lesion shown in Fig. 1a reduced in size after 2 weeks (arrow). d Lesion no longer demonstrated abnormal enhancement
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Background
Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory demyelinating disease of the central nervous system. We report a case of ADEM presenting with bilateral optic neuritis temporally associated with the ChAdOx1 vaccine against SARS-COVID19 virus.
Case presentation
A 36-year-old female presented with bilater...
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Background: Postmarketing surveillance of COVID-19 vaccination reveals that the COVID-19 vaccine administration is associated with several rare but serious neurological complications.
Case Report: We report a case of new-onset tumefactive demyelinating brain lesion that developed after administration of an adenovector-based COVID-19 vaccine. A midd...
Citations
... No significant differences were seen between individuals post/long-COVID (n=76) versus 44 normal/control subjects (n=44) controls in terms of visual evoked potentials (VEP). However, prolonged P100 latencies were observed in 12 patients post/long-COVID [108]. A 62-yearold male presented with asymptomatic left optic neuropathy and prolonged left P100 latency. ...
On the threshold of the COVID outbreak; electroencephalography (EEG) was used in diagnosis, crossborder disease differential diagnosis, disease-staging, monitoring of treatment, sedation and coma, in neuro-therapy and in declaration of brain death. EEG, quantitative EEG (QEEG), and standardized low resolution brain electromagnetic tomography (sLORETA) use entered the doldrums; reaching near “ceasure” due to COVID restrictions. Between 2020-2023, EEG use tipped, going from “Ceasure” to “First-Line” tool in triage, diagnosis, monitoring and therapy due to neurological, neurocognitive, neuropsychiatric, and neuromuscular sequelae of para- or acute- and post-COVID-19. The present paper will discuss this “Tipping point” in EEG, QEEG and sLORETA use.
... The appearance of ADEM is considered secondary to viral exposure, or less often (in 5% of cases) following vaccination [12,13]. Infections by various pathogens have been reported to result in ADEM-especially herpes simplex, coronaviruses, influenza, Epstein-Barr virus, cytomegalovirus, and measles [14,15]. ...
... Postvaccinal ADEM is described especially after influenza, varicella, measles, mumps, rabies, hepatitis B, diphtheria, and tetanus immunization [5,18]. Isolated case reports and case series in the current context of the last 3 years show a relationship between SARS-CoV-2 virus and ADEM, with both postviral and postvaccinal cases being described, secondary to the efforts made to combat Vaccines 2023, 11,1225 3 of 38 the pandemic [12,13]. Until now, there have been no large population studies to evaluate the incidence of these cases. ...
... Unlike in MS, the corpus callosum is spared [49,73]. MRI findings in ADEM may overlap with MS, but the latter is characterized by periventricular white matter, corpus callosum, and subcortical U fiber involvement [12,106]. Usually, the plaque borders in ADEM are not clearly defined. ...
Background:
The neurological complications of coronavirus disease 2019 (COVID-19) infection and the side effects of vaccination include immune-mediated diseases of the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM). It is an acute-onset demyelinating disease that involves a rapid evolution and multifocal neurological deficits that develops following a viral or bacterial infection or, less frequently, following vaccination. Acute hemorrhagic leukoencephalitis (AHLE) is the hemorrhagic variant of ADEM that presents a more severe evolution which can be followed by coma and death. The objectives of this study consist in evaluating the diagnosis, clinical characteristics, imaging and laboratory features, evolution, and treatment of ADEM and AHLE following COVID-19 infection or vaccination.
Methods:
We performed a systematic review of the medical literature according to PRISMA guidelines that included ADEM cases published between 1 January 2020 and 30 November 2022 following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination and also included our own clinical experience regarding this pathology.
Results:
A total number of 74 patients were diagnosed with ADEM, 45 following COVID-19 infection and 29 after a SARS-CoV-2 vaccine. A total of 13 patients (17.33%) presented AHLE. The moderate form of COVID-19 presented a positive correlation with AHLE (r = 0.691, p < 0.001). The existence of coma and AHLE was correlated with poor outcomes. The following more aggressive immunomodulatory therapies applied in severe cases were correlated with poor outcomes (major sequelae and death): therapeutic plasma exchange (TPE) treatment (r = 382, p = 0.01) and combined therapy with corticosteroids and TPE (r = 0.337, p = 0.03).
Conclusions:
Vaccinations are essential to reduce the spread of the COVID-19 pandemic, and the monitoring of adverse events is an important part of the strategic fight against SARS-CoV-2. The general benefits and the overall good evolution outweigh the risks, and prompt diagnosis is associated with a better prognosis in these patients.
... A notable observation in our analysis was the prevalence of ADEM as a reported neurological complication after The total number of studies included in the database searches N=89 14 Canadian Journal of Infectious Diseases and Medical Microbiology COVID-19 vaccination. ADEM is an autoimmune infammatory demyelinating disease of the CNS that usually occurs after viral infection or vaccination [43,45]. In our review, several ADEM cases were reported following vaccination with diferent COVID-19 vaccines such as mRNA-1273 (Moderna) [43], Pfzer-BioNTech [44,47,48], ChA-dOx1 (AstraZeneca) [35,45,50], and BIBP-CorV (Sinopharm) [46]. ...
... ADEM is an autoimmune infammatory demyelinating disease of the CNS that usually occurs after viral infection or vaccination [43,45]. In our review, several ADEM cases were reported following vaccination with diferent COVID-19 vaccines such as mRNA-1273 (Moderna) [43], Pfzer-BioNTech [44,47,48], ChA-dOx1 (AstraZeneca) [35,45,50], and BIBP-CorV (Sinopharm) [46]. Te onset of symptoms varied from a few days to several weeks after vaccination, and the MRI fndings showed multiple hyperintense lesions in diferent brain regions and spinal cord on T2-w and FLAIR sequences [43-48, 50, 103]. ...
Objective:
This systematic review aims to synthesize and analyze the available literature on central nervous system (CNS) magnetic resonance imaging (MRI) findings in individuals who have received COVID-19 vaccinations. Our objective is to enhance understanding of potential neurological side effects, inform clinical practice, and guide future research on the neurological implications of COVID-19 vaccination.
Methods:
In this systematic review, we conducted a comprehensive search in PubMed, Scopus, and Web of Science from January 2020 to April 2023, using terms related to COVID-19 vaccination and CNS MRI findings. We evaluated the quality of the study, extracted relevant data, and included 89 eligible studies that covered various vaccines, demographics of patients, symptoms, and MRI findings to provide a thorough understanding of SARS-CoV-2 vaccination-related CNS problems.
Results:
We investigated CNS MRI findings following COVID-19 vaccination across various vaccine types. Common diseases associated with post-vaccination CNS MRI findings included cerebral venous sinus thrombosis (CVST), vaccine-induced immune thrombotic thrombocytopenia (VITT), acute disseminated encephalomyelitis (ADEM), acute myelitis, autoimmune encephalitis (AE), and others. Patients presented with diverse onset symptoms and neurological manifestations. Abnormalities identified in CNS MRI findings included white matter (WM) hyperintensity. Our analysis offers a comprehensive overview of the current literature on post-vaccination CNS MRI findings. Discussion. We highlight a range of post-COVID-19 vaccination CNS MRI findings, including CVST, with a higher incidence in individuals receiving the ChAdOx1 (AstraZeneca) vaccine. Other notable observations include cases of ADEM, myelitis or transverse myelitis (TM), Guillain-Barré syndrome (GBS), and acute encephalopathy following COVID-19 vaccination. The incidence of these neurological complications is extremely rare, and the benefits of vaccination outweigh the risks. The reviewed studies were primarily case reports or case series, and thus large-scale epidemiological studies and controlled clinical trials are needed to better understand the underlying mechanisms and risk factors associated with these neurological complications following COVID-19 vaccination.
... Shimizu [12]. Nagaratnam et al. described the case of a 36-year-old female presenting with bilateral optic neuritis following her first dose of the ChAdOx1 vaccine with radiological evidence of ADEM [13]. Concomitant central and peripheral nervous system involvement in our patient in the form of ADEM, optic neuritis and mononeuritis multiplex, as a post COVID-19 vaccine neurological complication is an exceedingly rare event and probably not yet reported. ...
Background
Acute disseminated encephalomyelitis (ADEM) is an extremely rare complication of COVID-19 vaccination with very few reports worldwide. Concomitant peripheral nervous tissue involvement in ADEM is very uncommon.
Case presentation
We report the case of a 52 year aged lady who developed headache and focal neurological deficits after 10 days of COVID-19 vaccination. Her evaluation suggested ADEM with optic neuritis and mononeuritis multiplex. She responded to pulse methylprednisolone therapy.
Conclusions
COVID-19 vaccine may be associated with ADEM, optic neuritis and concurrent peripheral nervous system inflammation in rare instances.
... In fact, many corporations and agencies laid off employees due to vaccination mandates 3 . On the other hand, many studies report cases of demyelination following COVID-19 vaccinations among various other side effects [139,16,70,90,108,109,112,166,168,187,2,51,57,134] and specifically acute disseminated encephalomyelitis (ADEM) [196,8,28,146,152,161,145,78,199], acute encephalitis [24,52,63,66,117,123,195,129,157,199] [137,153,3,111,113,124,147,184,205], multiple sclerosis (MS) [82,108,114,11,121,140], myelin oligodendrocyte glycoprotein antibodyassociated disease (MOGAD) [95,114,151,121], neuromyelitis optica spectrum disorders (NMOSD) [21,40,108,114,122,121,140], optic neuritis [26,58,68,146,171,182], transverse myelitis [67,86,156,170,132,121], and tumefactive demyelinating brain lesion [53, 69,121]. ...
... In fact, many corporations and agencies laid off employees due to vaccination mandates 3 . On the other hand, many studies report cases of demyelination following COVID-19 vaccinations among various other side effects [139,16,70,90,108,109,112,166,168,187,2,51,57,134] and specifically acute disseminated encephalomyelitis (ADEM) [196,8,28,146,152,161,145,78,199], acute encephalitis [24,52,63,66,117,123,195,129,157,199] [137,153,3,111,113,124,147,184,205], multiple sclerosis (MS) [82,108,114,11,121,140], myelin oligodendrocyte glycoprotein antibodyassociated disease (MOGAD) [95,114,151,121], neuromyelitis optica spectrum disorders (NMOSD) [21,40,108,114,122,121,140], optic neuritis [26,58,68,146,171,182], transverse myelitis [67,86,156,170,132,121], and tumefactive demyelinating brain lesion [53, 69,121]. ...
We witnessed significant events during the COVID-19 pandemic. Home confinement for extended periods of time and product shortages were among the most common. WHO reports 768 million cases of COVID-19 and 6.9 million deaths as of June, 2023. Several vaccinations were approved by FDA under emergency use authorizations and 13.4 billion doses were delivered according to WHO. Now that COVID-19 is over as a pandemic, we are faced with its sequelae. One of the areas COVID-19 received research attention is its neuro-invasiveness. This study provides a short literature review about COVID-19 and demyelination in specific.
... There is increasing evidence that SC2Vs of any brand trigger the development of ADEM. It has been reported in several patients meanwhile [48,[61][62][63][64][65][66][67][68][69][70][71][72][73]. ...
SARS-CoV-2 vaccines are not free of side effects and most commonly affect the central or peripheral nervous system (CNS, PNS). This narrative review aims to summarise recent advances in the nature, frequency, management, and outcome of neurological side effects from SARS-CoV-2 vaccines. CNS disorders triggered by SARS-CoV-2 vaccines include headache, cerebro-vascular disorders (venous sinus thrombosis [VST], ischemic stroke, intracerebral hemorrhage, subarachnoid bleeding, reversible, cerebral vasoconstriction syndrome, vasculitis, pituitary apoplexy, Susac syndrome), inflammatory diseases (encephalitis, meningitis, demyelinating disorders, transverse myelitis), epilepsy, and a number of other rarely reported CNS conditions. PNS disorders related to SARS-CoV-2 vaccines include neuropathy of cranial nerves, mono-/polyradiculitis (Guillain-Barre syndrome [GBS]), Parsonage-Turner syndrome (plexitis), small fiber neuropathy, myasthenia, myositis/dermatomyositis, rhabdomyolysis, and a number of other conditions. The most common neurological side effects are facial palsy, intracerebral hemorrhage, VST, and GBS. The underlying pathophysiology is poorly understood, but several speculations have been generated to explain the development of CNS/PNS disease after SARS-CoV-2 vaccination. In conclusion, neurological side effects develop with any type of SARS-CoV-2 vaccine and are diverse, can be serious and even fatal, and should be taken seriously to initiate early treatment and improve outcome and avoid fatalities.
... Refs. [8][9][10] ). ...
... 10/17). Notably, later dyschromatopsia reversed in cases of macular retinopathy 9 or unilateral optic neuritis 11 ; however, CV worsening was recorded in a case of progressing bilateral optic neuritis 10 . ...
... In our final remark, we note that CV loss identified post-COVID in ophthalmological examination using the Ishihara test [8][9][10][11] conceivably captured moderate and/or relatively severe CV loss. Intended to diagnose red-green deficiencies, the Ishihara test cannot reveal subtle tritan defects 23 , as those that we identified in more than half of pCPs by employing the FM-100. ...
Post-COVID-19, recorded were various ophthalmological symptoms and visual impairment. We hypothesised that colour vision may be affected too. We assessed colour discrimination using the Farnsworth-Munsell 100 Hue test (FM-100) in individuals, who have had COVID-19 (N=77; 18–68 years). Total error score (TES) indicated superior colour discrimination in 34 observers. The Vingrys–King-Smith C-index (severity) exceeded the normal cutoff measure in 44 observers. In participants (N=35) with average TES, the Vingrys–King-Smith analysis revealed subtle colour deficiencies – either a mild tritan defect (‘blue’ or blue-yellow) or moderate defect with a diffuse error pattern. A minor sub-sample (N=6) manifested poor discrimination or colour vision loss (N=2), with a tritan or diffuse error pattern. √TES negatively correlated with the recovery time lapse. Partial error scores (√PES) indicated prevailing B–Y errors, regardless of the elapsed post-illness period. Overall, the results indicate that about half of those who have recovered from COVID-19 reveal predominantly mild Type III acquired colour discrimination loss, characteristic of retinal disorders and vascular disease. Conceivably, coronavirus infection caused hypoperfusion (reduced vascular supply) at the retinal and/or post-retinal stages of the visual system having affected neural mechanisms of colour discrimination. The mild impairment appears to be reversible with a favourite prognosis.
... A literature review identified 173 additional cases of CNS neuroinflammatory disease after either SARS-CoV-2 infection or vaccination, with 65 cases of transverse myelitis, 30 cases of optic neuritis, and 78 cases of encephalomyelitis (Table). [7][8][9][10][11][12][13][14][15] Most of these cases occurred within 2-3 weeks of either the infection or vaccination as with our patient, although the vast majority of cases in the literature (>70% of each phenotype) occurred in association with infection. Transverse myelitis and encephalomyelitis tended to occur closer to the time of vaccination or infection. ...
... Regardless of the type of demyelinating event, all events were far more likely (73% of transverse myelitis, 77% of optic neuritis, and 74% of encephalomyelitis) to occur in association with SARS-CoV-2 infection in comparison to vaccination. [7][8][9][10][11][12][13][14][15][16][17][18] Our case was unusual in the degree of brain and spinal cord involvement, particularly the perivascular distribution of the inflammation, as well as the insidious degree of inflammation, with symptoms progressing over several months. Vascular complications and endothelial dysfunction have become increasingly identified in COVID-19, possibly mediated by SARS-CoV-2 targeting angiotensin-converting enzyme 2 receptors that are expressed in multiple organs, including the brain, although the exact pathogenesis remains unknown. ...
Prior case studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines may unmask CNS neuroinflammatory conditions. We present a case of relapsing steroid-responsive encephalomyelitis after SARS-CoV-2 infection and subsequent COVID-19 vaccination. We also characterize the frequency of CNS neuroinflammatory events reported in the literature after both SARS-CoV-2 infection and COVID-19 vaccination.
... Several studies have reported ADEM occurrence after SARS-CoV-2 infection [15][16][17]. Moreover, a large number of case reports and case series have also suggested the potential association between ADEM and COVID-19 vaccination [18][19][20][21][22][23]. ...
Background:
Although global vaccination against COVID-19 infection has its excellence, potential side effects are yet of concern. Several lines of evidence have proposed ADEM occurrence after SARS-CoV-2 infection. Moreover, a large number of case reports and case series have also suggested the casual association between ADEM and COVID-19 vaccination. To better understand the development of ADEM following COVID-19 vaccination and its potential association, we aimed to systematically review ADEM cases reported after COVID-19 vaccination.
Methods:
We conducted a comprehensive systematic search using three databases including PubMed, Scopus, and Web of Science. Studies that reported ADEM after COVID-19 vaccination were eligible to include in our study. Observational studies, case reports, and case series which reported cases of ADEM with sufficient detail to confirm clinical diagnosis following COVID-19 vaccination were eligible to enter our study.
Results:
Twenty studies were included in our systematic review after the abstract and full-text screening with a total of 54 cases. Among included patients, 45 (85.1 %) developed ADEM after the first dose of the COVID-19 vaccine, and seven (12.9 %) cases experienced ADEM after the second dose. The median time interval between vaccination and neurological symptoms was 14 days which ranged from 12 h to 63 days. Twelve (22.2 %) patients experienced symptoms of muscle weakness, ten (18.5 %) presented unconsciousness, nine (16.6 %) patients had urinary complaints, nine (16.6 %) had visual impairments, and five (9.2 %) experienced a seizure. After treatments, four (13.8 %) patients died. Forty-six patients had clinical improvement (85.1 %), also improvement in brain MRI was observed among 44 (81.4 %) patients.
Conclusion:
In conclusion, it is not clear that ADEM could be a potential complication of COVID-19 vaccination based on the current evidence and further studies are needed. However, this rare condition should not trigger stopping the mass vaccination programs since the only way to eradicate the current pandemic of COVID-19 is to extend the number of immunized people.
... 4,5 Upon global uptake of COVID-19 vaccines, a number of reports have described various presentations of acute central nervous system (CNS) inflammation in individuals shortly after vaccination. This includes new onset multiple sclerosis (MS), [6][7][8] MS relapse, 6,9 transverse myelitis (TM), 4,10-13 myelin oligodendrocyte glycoprotein antibody disease (MOGAD), 14,15 neuromyelitis optica spectrum disorder (NMOSD), 6,[16][17][18] acute disseminated encephalomyelitis (ADEM), [19][20][21] leucine-rich glioma-inactivated protein 1 (LGI1) antibody encephalitis, 22 and seronegative autoimmune limbic encephalitis. 23 Vaccination has long been speculated to increase the risk of CNS inflammatory events, most notably demyelinating diseases such as ADEM. ...
Background:
Reports suggest a potential association between coronavirus disease 2019 (COVID-19) vaccines and acute central nervous system (CNS) inflammation.
Objective:
The main objective of this study is to describe features of acute CNS inflammation following COVID-19 vaccination.
Methods:
A retrospective observational cohort study was performed at the BARLO MS Centre in Toronto, Canada. Clinicians reported acute CNS inflammatory events within 60 days after a COVID-19 vaccine from March 2021 to August 2022. Clinical characteristics were evaluated.
Results:
Thirty-eight patients (median age 39 (range: 20-82) years; 60.5% female) presented within 0-55 (median 15) days of a receiving a COVID-19 vaccine and were diagnosed with relapsing remitting multiple sclerosis (MS) (n = 16), post-vaccine transverse myelitis (n = 7), clinically isolated syndrome (n = 5), MS relapse (n = 4), tumefactive demyelination (n = 2), myelin oligodendrocyte glycoprotein antibody disease (n = 1), neuromyelitis optica spectrum disorder (n = 1), chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (n = 1) and primary autoimmune cerebellar ataxia (n = 1). Twenty-two received acute treatment and 21 started disease-modifying therapy. Sixteen received subsequent COVID-19 vaccination, of which 87.5% had no new or worsening neurological symptoms.
Conclusion:
To our knowledge, this is the largest study describing acute CNS inflammation after COVID-19 vaccination. We could not determine whether the number of inflammatory events was higher than expected.
