Update on Acute Disseminated Encephalomyelitis in Children and Adolescents

Massa, Serena; Fracchiolla, Adriana; Neglia, Cosimo; Argentiero, Alberto; Esposito, Susanna

doi:10.3390/children8040280

Cited by 27 publications

(32 citation statements)

References 57 publications

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“…ADEM, a form of autoimmune encephalitis, is an immune-mediated, inflammatory demyelinating disease of the central nervous system that can affect children and young adults after infections or immunizations [68] and was reported in two cases [31,32] in the present review. The mean age of onset is between 3.6 and 7 years, without differences in sex [69].…”

Section: Discussionmentioning

confidence: 76%

“…The mean age of onset is between 3.6 and 7 years, without differences in sex [69]. In the pathogenesis, the molecular mimicry between microbial epitopes and myelin antigens such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) is considered the most important mechanism of the immune-mediated injury [68,70].…”

Section: Discussionmentioning

confidence: 99%

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A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection

O'Loughlin

Toledo

Budrie

et al. 2021

Neurology International

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SARS-CoV-2 infection in children produces mild respiratory symptoms or no symptoms at all in most cases. Some pediatric patients develop a severe complication associated with high mortality, the multisystem inflammatory syndrome in children (MIS-C). In both scenarios, there are reports of neurological manifestations. This article aims to review the cases of pediatric patients with severe neurological issues and a coexisting positive SARS-CoV-2 test. A literature search was performed between March 2020 and May 2021. The results included the data from 41 studies, with 159 children with severe neurological manifestations, within an age range from 24 h to 17 years. The neurological disorders included 38 cases with stroke, 32 with encephalitis, 22 with encephalopathy, and 10 with Guillain–Barre syndrome. Sixty-five out of 159 cases with severe neurological manifestations were diagnosed with MIS-C. Direct neuroinvasion and the exaggerated immune response in some patients seem to be the most critical factors triggering these manifestations. Further research in the ongoing pandemic is needed to elucidate the precise mechanism.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection

O'Loughlin

Toledo

Budrie

et al. 2021

Neurology International

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“…Patients with classic ADEM usually have a good outcome with a complete recovery. The outcome seems to be better in children than in young adults, especially for the disease course, recovery, and mean duration of hospitalization [ 45 ]. Unlike typical ADEM, most of COVID-19-related ADEM have a relatively poor outcome, with mortality rates of 10% (Table 4 ).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature

Wang

Huo

et al. 2021

J Neurol

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The literature on cases of acute disseminated encephalomyelitis (ADEM) associated with SARS-CoV-2 infection has been rapidly increasing. However, the specific clinical features of ADEM associated with SARS-CoV-2 (SARS-CoV-2-ADEM) have not been previously evaluated. We screened all articles resulting from a search of PubMed and Web of Science databases looking for reports of ADEM published between December 01, 2019, and June 5, 2021. Of the 48 ADEM cases identified from 37 studies, 34 (71%) had ADEM while 14 (29%) were of AHLE. RT-PCR for SARS-CoV-2 was positive in 83% ( n = 19) of patients. 26 patients (54%) were male, and 18 patients (38%) were female, with a male to female sex ratio of 1.4:1; median age was 44 (1.4–71) years. 9 patients (19%, 9/48) were children. Of the 9 children patients, their median age was 9 years (range 1.4–13 years), 6 patients (67%) were female, and 2 patients (22%) were male, with a female to male sex ratio of 3:1.39 patients (81%) was performed CSF analysis. PCR for SARS-CoV-2 tested positive in 3 patients (14%, 3/22) on CSF sample. 31 (64%) of patients had a poor outcome on discharge from hospital. Five (10%) patients died in hospital. Compared to classic ADEM, SARS-CoV-2-ADEM have a more longer duration between the onset of the antecedent infective symptoms and the start of ADEM symptoms, the older age distribution of the patients, relatively poor outcome, a lower full recovery rate, a more frequently brain lesions involved the periventricular white matter and corpus callosum, and less frequently affected the deep gray matter. Taken together, the present comprehensive review reveals that although rare, ADEM can be associated with SARS-CoV-2 infection. SARS-CoV-2-ADEM seems to share most features of classic ADEM, with moderate discrepancies from the classical ADEM.

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“…In ADEM, MOG antibodies may be present in serum in up to 50% of cases [ 51 ], and this condition can be considered a spectrum of MOG-associated disorders [ 52 ]. Molecular mimicry of viral or bacterial antigenic determinants with myelin autoantigens such as MOG—but also myelin basic protein (MBP), myelin-associated oligodendrocyte basic protein (MOBP), oligodendrocyte-specific protein (OSP), and proteolipid protein (PLP)—has been hypothesized.…”

Section: Immunity and Neuroinflammationmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders

Allegretta

D’Amico

Manuti

et al. 2022

IJMS

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Autoimmune demyelinating diseases—including multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein-associated disease, acute disseminated encephalomyelitis, and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis—are a heterogeneous group of diseases even though their common pathology is characterized by neuroinflammation, loss of myelin, and reactive astrogliosis. The lack of safe pharmacological therapies has purported the notion that cell-based treatments could be introduced to cure these patients. Among stem cells, mesenchymal stem cells (MSCs), obtained from various sources, are considered to be the ones with more interesting features in the context of demyelinating disorders, given that their secretome is fully equipped with an array of anti-inflammatory and neuroprotective molecules, such as mRNAs, miRNAs, lipids, and proteins with multiple functions. In this review, we discuss the potential of cell-free therapeutics utilizing MSC secretome-derived extracellular vesicles—and in particular exosomes—in the treatment of autoimmune demyelinating diseases, and provide an outlook for studies of their future applications.

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Update on Acute Disseminated Encephalomyelitis in Children and Adolescents

Cited by 27 publications

References 57 publications

A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection

A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection

SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders

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