Sex: F
Vaccine: COVID19
Symptoms: Magnetic resonance imaging thoracic, Metabolic function test, Microbiology test, Neurological examination, Physical examination
Clinical narrative: Acute disseminated encephalomyelitis (ADEM)-like illness; This is a literature report.  A 10-year-old female patient received bnt162b2 (BNT162B2), on 29Nov2021 as dose 2 (orange cap), single (Batch/Lot number: unknown) for covid-19 immunisation. The patient had no relevant medical history. The patient's concomitant medications were not reported. Vaccination history included: Covid-19 vaccine (dose 1, manufacturer unknown), for Covid-19 immunisation. The following information was reported: ACUTE DISSEMINATED ENCEPHALOMYELITIS (hospitalization, medically significant) with onset 14Dec2021, outcome "not recovered", described as "Acute disseminated encephalomyelitis (ADEM)-like illness". The patient was hospitalized for acute disseminated encephalomyelitis (start date: 21Dec2021, discharge date: 30Dec2021, hospitalization duration: 10 day(s)). Therapeutic measures were taken as a result of acute disseminated encephalomyelitis.  The clinical course is as follows: A patient with no past medical history presented to the hospital on 21Dec2021 with 7 days of progressive lower extremity weakness, paresthesia, and urinary retention. No recent symptoms of infection were reported. Neurological examination showed mild lower extremity hyperreflexia, right lower extremity weakness with inability to ambulate, a mild pronator drift, and a right visual field defect. The patient received her second dose of mRNA-based COVID-19 vaccine 16 days prior to the onset of symptoms. Upon admission, a comprehensive laboratory assay including CBC, CMP, ESR, and CRP, was negative. A respiratory viral panel which included SARS-COV2 PCR testing was negative. Contrast-enhanced MRI of the brain demonstrated multiple prominent T2/fluid attenuation inversion recovery (FLAIR) image hyperintense subcortical and deep white matter lesions with incomplete rim-enhancement, compatible with active demyelination, and avid peripheral diffusion restriction (Initial brain MRI findings. Left: Axial FLAIR image demonstrating multifocal supratentorial subcortical and deep white matter lesions. Middle: Axial T1 post-contrast image demonstrating peripheral lesion enhancement. Right: Axial diffusion-weighted imaging [DWI] image demonstrating avid peripheral diffusion restriction.). Contrast-enhanced MRI of the cervical, thoracic, and lumbar spine demonstrated a long-segment, non-expansile, partially enhancing intramedullary lesion within the thoracic spinal cord, also most likely compatible with active demyelinating process (Initial thoracic spine MRI findings. Left: Sagittal short tau inversion recovery [STIR] image demonstrating multiple longitudinally extensive spinal cord lesions. Right: Sagittal T1 post-contrast image demonstrating corresponding lesion enhancement.). There were no findings suggestive of Guillain-Barre syndrome. Secondary differential considerations included transverse myelitis, CNS lymphoma, and atypical multiple sclerosis. Lumbar puncture was performed, and CSF analysis showed an isolated leukocytosis with normal protein and glucose levels. A comprehensive autoimmune and infectious CSF panel was obtained, with results pending. On hospital day 2, the patient underwent stereotactic right parietal lobe biopsy, given the diagnostic risk of initiating steroid treatment before fully excluding lymphoma. She then began a 5-day course of i.v. corticosteroids. On hospital day 5, examination showed subtle improvement in motor strength, and resolution of pronator drift. The following day her motor strength continued to improve, and she regained urinary continence. On hospital day 7, CSF autoimmune screening for antibodies associated with demyelinating disorders (including MOG, AQP4, and gangliosides) resulted negative. Microbiology studies (including HSV, VZV, CMV, EBV, and HIV) were also negative, and a CSF flow cytometry showed no evidence of lymphoproliferative neoplasm. On hospital day 8, the patient began intravenous immunoglobulin (IVIG) treatment and transitioned to oral corticosteroids. On hospital day 9, oligoclonal band testing returned normal. By hospital day 10, the patient remained afebrile, hemodynamically stable, and made full recovery of bowel, bladder, and sensory function. Motor strength significantly recovered with physical therapy, but there was a mild, persistent gait unsteadiness. She was safely discharged the same day. Three months after initial evaluation, the patient returned for outpatient neurologic follow-up. She reported mild fatigue. Examination showed a mild, persistent gait instability and hip muscle weakness. All other symptoms were resolved. A few days later, final histopathology showed white matter neurons with an extensive macrophage-rich inflammatory infiltrate with small lymphocytic component forming perivascular aggregates. Luxol/H&E stain showed severe loss of myelin, with macrophages demonstrating phagocytosed myelin debris. Immunohistochemistry showed depletion, but relative preservation of axons, with scattered perivascular accumulations of CD3+ T-cells and CD4/CD8 co-expressing T-cells. One month later, a follow-up non-contrast MRI of the brain was performed, since the patient's parent declined contrast-enhanced MRI. This showed residual, but substantially decreased size and FLAIR signal abnormality of the lesions (Follow up brain MRI findings. Left: Axial FLAIR image demonstrating decreased FLAIR signal hyperintensity of the white matter lesions. Middle: Axial non-contrast T1 image demonstrating lesion signal characteristics relatively isointense to grey matter. Right: Axial DWI image demonstrating decreased diffusion restriction of the lesions.). ADEM is a rapidly progressive autoimmune condition that causes multiple demyelinating inflammatory lesions in the brain and spinal cord. The diagnosis should be suspected in a child who develops acute polyneuropathy in the setting of recent infection or immunization. In this case, these clinical findings improved significantly with corticosteroid and IVIG therapy and are most compatible with ADEM or an ADEM-like clinically isolated syndrome. Notably, the patient did not exhibit encephalopathy, which some authors suggest is a major diagnostic criterion for ADEM. Whether ADEM or a related clinically isolated syndrome, this disease spectrum is strongly supported by the histopathological findings of patchy inflammatory infiltrates with perivascular lymphocytic aggregates, which Agency observed is more strongly associated with ADEM than other demyelinating diseases. There are little data characterizing a link between COVID-19 vaccination and ADEM. In this case, a similar time course between COVID-19 vaccination and disease onset is observed when compared to other adult cases. The author's findings are also congruent with the hypothesis of Rinaldi et al, that T-cell lymphocytic infiltrate found in ADEM pathophysiology is consistent with the ability of COVID-19 vaccines to catalyze a T-cell mediated immune response. Nonetheless, present understanding of both mechanisms remains incomplete.  No follow-up attempts are possible. No further information is expected.; Sender's Comments: Based on the available information and implied temporal association, a causal relationship between the reported event Acute disseminated encephalomyelitis and suspect product cannot be excluded. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.