key: cord-0816034-v7ajx113 authors: Lazaro, Luciana G.; Perea Cossio, Jhon E.; Luis, Maria B.; Tamagnini, Flavia; Paguay Mejia, Diego A.; Solarz, Horacio; Fernandez Liguori, Nora A.; Alonso, Ricardo N. title: Acute disseminated encephalomyelitis following vaccination against SARS-CoV-2: A case report date: 2022-03-01 journal: Brain Behav Immun Health DOI: 10.1016/j.bbih.2022.100439 sha: c35128bf938e583d8c931bb7751e9124512c8134 doc_id: 816034 cord_uid: v7ajx113 Acute disseminated encephalomyelitis (ADEM) is an inflammatory emyelinating disease of the central nervous system that is usually considered a monophasic disease Post-vaccination ADEM has been associated with several vaccines, however, there is scarce information related to SARS-CoV-2 vaccines. We present the case of a 26- year-old female who suffered from ADEM four weeks after Gam-COVID-Vac administration. Acute disseminated encephalomyelitis (ADEM) is a monophasic acute non-vasculitic inflammatory demyelinating disorder of the central nervous system (CNS) characterized by diffuse neurologic signs and symptoms coupled with evidence of multifocal lesions of demyelination on neuroimaging [1] . Pathogenesis is suspected to be related to an autoimmune response to myelin triggered by infection or immunization via molecular mimicry [2] . ADEM most often occurs in childhood and it has been estimated to account for 10-15% of acute encephalitis cases in the United States [3] . Uniform diagnostic criteria did not exist until the expert-defined consensus developed by the International Pediatric Multiple Sclerosis Society Group published in 2007, which was updated in 2013 [4] . However, these criteria have only been performed for the pediatric population and we have not yet had criteria for the adult population. Since the SARS-CoV-2 infection has been declared a global pandemic, vaccines have become one the most important strategies to reduce mortality. In response, massive vaccination campaigns have been developed around the world [5] . Post-vaccination ADEM has been associated with several vaccines, however, there is scarce information related to SARS-CoV-2 vaccines [6] . We present the case of a 26year-old female who suffered from ADEM four weeks after Gam-COVID-Vac administration. The patient was admitted after 10 days of disorientation, inappropriate behavior, headache and gait imbalance. She had no personal history of infection, fever or weight loss. Her family history was negative for autoimmune diseases. Four weeks before admission she received a first dose of Gam-COVID-Vac vaccine (human adenovirus viral vector). The initial examination revealed deferred memory, hypoprosexia, anosognosia, incoherent speech and visuospatial failures. Right upper limb weakness and gait ataxia were also noted. Brain Magnetic Resonance Imaging (MRI) showed nodular hyperintense lesions on T2-weighted image and fluid attenuated inversion recovery without restricted diffusion on diffusion. Marked vasogenic edema and T1-weighted image post contrast incomplete annular enhancement was observed (FIG 1) . The cerebrospinal fluid (CSF) contained 3 cells, 50 grams proteins/L, normal glucose. Oligoclonal bands (OCB) were positive. An extensive microbiological investigation, including CSF markers for viral and bacterial agents responsible for encephalitis showed no evidence of recent infection. Anti-myelin oligodendrocyte glycoprotein antibody (anti-MOG) IGG was negative. Chest, abdomen and pelvis computed tomography, breast and gynecological ultrasound ruled out a neoplasm (Table 1) . A brain biopsy confirmed a perivascular demyelination and reactive astrocytosis (FIG 2) . Postvaccinal ADEM was suspected and the patient was treated with intravenous methylprednisolone 1000 mg daily over 5 days. The clinical course was favourable. Her neurological examination was normal. The MRI was repeated after three months, showing clear imaging improvement of all the lesions (FIG 3) . Post-vaccination reactions have declined with the use of recombinant proteins compared to those based on in vivo infected animal tissue [7] . In the present, postinfectious and post-immunisation encephalomyelitis represent about three-quarters of ADEM cases [8] . Post-vaccination ADEM is associated with several vaccines including those against rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza and hepatitis B [9] . Incidence rates are as low as 0.1 to 0.2 per 100,000 vaccinated individuals [10] and it seems to occur much more frequently after the first dose rather than revaccination [11] . Although it is an underdiagnosed pathology, the estimated incidence in children and adolescents is 0.8 per 100,000 inhabitants per year [12] . The incidence in the adult population is not exactly known. There are few case series that describe the presentation of this pathology in the adult population [13] . Regarding the vaccine against SARS-CoV-2 Xintong Li et al reported populationbased, age and sex specific background incidence rates of potential adverse events of special interest (AESI) in adults in eight countries using thirteen databases [6] . For both men and women, ADEM was a very rare entity (<1/10,000) in individuals under 64 years, and rare (1/1,000 to 1/10,000) in those of 65 years and older [6] . Roman et al have described 3 acute transverse myelitis after vaccination with ChAdOx1 nCoV-19 (AZD1222), thus, this review has identified possible CNS demyelination events after the vaccine [14] . ADEM lesions are typically bilateral, asymmetrical, large (>2 cm) and poorly demarcated. Both white and gray matter can be affected. Cortical as well as deep gray matter lesions have been described [15] . Gadolinium enhancement is not a typical finding, although it has been reported in up to 30% of cases [16] . Our patient´s MRI, with multiple lesions and anatomic areas with mass effect and ring enhancement, is compatible with ADEM according to the International Pediatric Multiple Sclerosis Study Group [4] . Based on the imaging features and positive OCB, other CNS demyelinating diseases should be considered as differential diagnoses. Despite our patient clinical and imaging improvement after corticosteroid therapy, it can be the beginning of a tumefactive multiple sclerosis (MS). Since the images can be similar in both diseases, the following pathological findings can generally help to differentiate between ADEM and MS. There are demyelination "sleeves" surrounding the venules associated with significant inflammatory infiltrates dominated by T lymphocytes and macrophages. Another feature is pronounced inflammation with only minor demyelination restricted to the vicinity of perivascular inflammatory infiltrates and that all lesions must be of the same age [17] . The biopsy of one of our patient's lesions showed this demenilization and perivascular inflammatory infiltrate. Another differential diagnosis is myelin oligodendrocyte glycoprotein antibodyassociated disorders (MOGAD) with ADEM-like presentacion. In both, ADEM and MOGAD, the clinical condition is similar. There are changes in mental status and increased frequency of seizures [18] . In adults with the positive anti-MOG test, ADEM presentation varies from a few up to 18% of cases [19] . Therefore at this low frequency, the anti-MOG IGG dosage is recommended[20]. Our patient had a negative anti-MOG antibody for cell-based assays (CBAs). This method for detection of anti-MOG antibody has a specificity close to 100% [21] . The association between the SARS CoV-2 vaccination and ADEM has emerged in recent months, hence, up to now no large population studies or estimated incidence rates are known. Vaccine safety must continue to be monitored to complement what has initially been learned during clinical development. In a recently vaccinated patient, if neurological manifestations and neuroimaging features suggested ADEM, appropriate treatment with corticosteroid pulses, plasmapheresis, or immunoglobulin should be started to prevent sequelae. Our patient has met the ADEM diagnostic criteria set by the International Pediatric MS Study Group. Other alternatives have been excluded. An association with the vaccine has been suspected. This does not mean that vaccines pose a risk that does not outweigh their benefit. Up to now, based on the positive result of the OCB, the onset of pseudotumoral MS cannot be ruled out. 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