Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalitis Following COVID-19: Systematic Review and Meta-synthesis.

BACKGROUND AND OBJECTIVES: Since the onset of the COVID-19 pandemic, a growing number of reports have described cases of acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE) following infection with COVID-19. Given their relatively rare occurrence, the primary objective of this systematic review was to synthesize their clinical features, response to treatments, and clinical outcomes to better understand the nature of this neurologic consequence of COVID-19 infection. METHODS: Patients with a history of COVID-19 infection were included if their reports provided adequate detail to confirm a diagnosis of ADEM or AHLE by virtue of clinical features, radiographic abnormalities, and histopathologic findings. Cases purported to be secondary to vaccination against COVID-19 or occurring in the context of a preexisting relapsing CNS demyelinating disease were excluded. Case reports and series were identified via PubMed on May 17, 2021, and 4 additional cases from the authors' hospital files supplemented the systematic review of the literature. Summary statistics were used to describe variables using a complete case analysis approach. RESULTS: Forty-six patients (28 men, median age 49.5 years, 1/3 >50 years old) were analyzed, derived from 26 case reports or series originating from 8 countries alongside 4 patient cases from the authors' hospital files. COVID-19 infection was laboratory confirmed in 91% of cases, and infection severity necessitated intensive care in 67%. ADEM occurred in 31 cases, whereas AHLE occurred in 15, with a median presenting nadir modified Rankin Scale score of 5 (bedridden). Anti-MOG seropositivity was rare (1/15 patients tested). Noninflammatory CSF was present in 30%. Hemorrhage on brain MRI was identified in 42%. Seventy percent received immunomodulatory treatments, most commonly steroids, IV immunoglobulins, or plasmapheresis. The final mRS score was ≥4 in 64% of patients with adequate follow-up information, including 32% who died. DISCUSSION: In contrast to ADEM cases from the prepandemic era, reported post-COVID-19 ADEM and AHLE cases were often advanced in age at onset, experienced severe antecedent infection, displayed an unusually high rate of hemorrhage on neuroimaging, and routinely had poor neurologic outcomes, including a high mortality rate. Findings are limited by nonstandardized reporting of cases, truncated follow-up information, and presumed publication bias.

Outcome of children with acute disseminated encephalomyelitis in a tertiary care center in India.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated disease of the brain that follows viral infection or vaccination, or even appears spontaneously. The objective of the study was to evaluate the clinical, neuroimaging and laboratory profiles of children with ADEM. Seventeen children admitted to the Pediatric Department of Dayanand Medical College and Hospital, Ludhiana, whose cases were consistent with the diagnosis of ADEM, were included. Their clinical and neuroimaging profiles and outcomes were studied. The most common presenting features were fever (71%), altered sensorium (59%) and headache and convulsions (41%). Brain MRI identified lesions in subcortical white matter (75%) and periventricular white matter (38%). Most patients were treated with corticosteroids. A favorable outcome was seen in 88% of patients. Although 59% of patients had neurologic sequelae at discharge, only one patient had a major neurological deficit at follow-up. Prognosis for survival and outcome was good in the majority of patients. Neurological sequelae at discharge do not predict poor outcome.

A mouse-based assay for the pre-clinical neurovirulence assessment of vaccinia virus-based smallpox vaccines.

Post-vaccinal encephalitis, although relatively uncommon, is a known adverse event associated with many live, attenuated smallpox vaccines. Although smallpox vaccination ceased globally in 1980, vaccine manufacture has resumed in response to concerns over the possible use of smallpox virus as an agent of bioterrorism. To better support the production of safer smallpox vaccines, we previously reported the development of a mouse model in which a relatively attenuated vaccine strain (Dryvax) could be discerned from a more virulent laboratory strain (WR). Here we have further tested the performance of this assay by evaluating the neurovirulence of several vaccinia virus-based smallpox vaccines spanning a known range in neurovirulence for humans. Our data indicate that testing of 10-100 pfu of virus in mice following intracranial inoculation reliably assesses the virus's neurovirulence potential for humans.

Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse.

To date, there is no available epidemiological study about prognostic factors of acute disseminated encephalomyelitis (ADEM) in children, using a cohort of patients with homogenous inclusion criteria. We aimed to evaluate prognostic factors for relapse after ADEM in children. A total of 132 children from the French National KIDSEP Neuropediatric Cohort (mean age at onset: 6+/-3.3 years; mean follow-up: 5.4+/-3.3 years; lost to follow-up: 10%). ADEM diagnosis was considered in a previously healthy patient acutely presenting more than one neurological deficit, change in mental state and MRI alterations including white matter changes. We used multivariate survival analysis (Cox model) evaluating the prognostic value of baseline clinical, biological and MRI covariates, for the occurrence of a second attack. Twenty-four (18%) of included patients had a second attack. An increased risk of relapse was associated with optic neuritis (hazard ratio, 5.23; 95% CI, 2-13.65), familial history of central nervous system inflammatory demyelination (7.79; 1.54-39.5), Barkhof multiple sclerosis (MS) criteria on MRI (2.52; 1.04-6.12) and no neurological sequelae after first attack (3.79; 1.12-12.85). Clinical and MRI prognostic factors for relapse in ADEM may contribute to an early distinction between monophasic and relapsing disease, which may be related to MS.

Early diagnostic magnetic resonance imaging in acute disseminated encephalomyelitis.

We report two cases and review the literature concerning the importance of early magnetic resonance imaging (MRI) of the brain as a guide for the early diagnosis and treatment of acute disseminated encephalomyelitis (ADEM). A nonspecific term, ADEM refers to an acute disease that is postinfectious, parainfectious, postvaccinal, or of an unknown precipitating factor. Often when there is clinical suspicion of ADEM, MRI is not done before significant morbidity and mortality occur, despite the existence of adequate treatments. Primary care physicians should be aware of the importance of early MRI in ADEM.

Encefalomielitis aguda diseminada postinfecciosa / No disponible

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Encephalitis and aseptic meningitis, Olmsted County, Minnesota, 1950-1981: I. Epidemiology.

All cases fulfilling stated criteria for encephalitis and aseptic meningitis in Olmsted County, Minnesota, for the period 1950 through 1981 were identified. This is, to our knowledge, the first such incidence and trend study in a delineated population, providing rates per 100,000 person-years of 7.4 for encephalitis (189 cases) and 10.9 for aseptic meningitis (283 cases). These are about twelve and six times higher, respectively, than the rates reported by the Centers for Disease Control. The rates have been stable over successive 5- or 10-year periods except for a recent increase in aseptic meningitis. Both conditions were more common in the summer months, in childhood, and among males. Viral identification using conventional laboratory tests has improved with time; in the period 1970 through 1981, virus type was specified in about one-fourth of the cases. The most common agents identified were California and mumps viruses in encephalitis, and entero and mumps viruses in aseptic meningitis. Antecedent and/or concurrent infections were noted in 42 and 35% of encephalitis and aseptic meningitis cases, respectively. No case due to mumps, measles, or rubella viruses has occurred since 1972, reflecting the impact of immunizations. Recovery was reported at the end of the acute phase in 95% of patients with aseptic meningitis, and there were no deaths. Seventy-eight percent of encephalitis patients recovered completely; the case fatality rate was 3.8%. Of the encephalitis cases, 2% were diagnosed initially postmortem.