This condition more commonly affects children and is often a monophasic illness with good functional recovery. ongoing neurocognitive sequelae. Further research related to the optimal management of pediatric ADEM and its impact on prognosis is needed. This review summarizes the current knowledge of the pathogenesis, epidemiology, clinical features, diagnostic evaluation, treatment approaches, and outcomes in pediatric ADEM. Key Points Acute disseminated encephalomyelitis can have many different presenting features, but the hallmark is multifocal neurological deficits associated with encephalopathy. Diagnostic workup involves serum and spinal fluid studies to investigate infectious and inflammatory causes and neuroimaging to characterize the extent of central nervous system involvement.Acute therapies such as high-dose intravenous corticosteroids, therapeutic plasma exchange, and intravenous immunoglobulin are aimed at Rabbit Polyclonal to MSH2 reducing inflammation and generally lead to marked clinical improvement. Long-term follow-up of pediatric patients is essential to mitigate any potential neurological or psychosocial sequelae of the condition. Open MDL-800 in a separate window Introduction Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS) that typically presents with encephalopathy and multifocal brain lesions. This condition more commonly affects children and is often a monophasic illness with good functional recovery. Diagnostic testing should be aimed at differentiating ADEM from potential infectious, toxic/metabolic, genetic, vascular, and neoplastic mimics. It is also important to consider whether ADEM represents the first attack of a relapsing inflammatory demyelinating syndrome, particularly myelin oligodendrocyte glycoprotein (MOG) antibody disease or, less likely, multiple sclerosis or neuromyelitis optica spectrum disorder (NMOSD). Once testing is sufficiently suggestive of an acute demyelinating syndrome, it is critical that treatments directed at reducing inflammation and immune activation are started to decrease the duration and severity of the illness. Early initiation of physical, occupational, and speech therapy, when applicable, can help facilitate earlier and more complete recovery. While long-term prognosis and physical functioning is good, increasing data suggest that children with ADEM can have persistent neurocognitive deficits. A multidisciplinary approach to the follow-up of a child with ADEM, involving the expertise of neurologists, neuropsychologists, and physiatrists, among other clinicians, is important to optimize disease recovery and facilitate surveillance for potential relapses of acute demyelination. Pathogenesis ADEM is postulated to be an autoimmune disorder in which an environmental stimulus triggers a dysfunctional, exaggerated immune response in genetically susceptible individuals [1]. ADEM has also been referred to as post-infectious encephalomyelitis based on this suspected mechanism of a pathogen triggering the aberrant immune response. It is thought that myelin constituents such as myelin basic protein, MOG, and myelin proteolipid protein share antigenic determinants with that of an inciting pathogen in a process termed molecular mimicry [2, 3]. Many pathogens have been reported to have an association with ADEM, including measles, rubella, varicella zoster, influenza, EpsteinCBarr virus, herpes simplex virus (HSV), enterovirus, coxsackievirus, mycoplasma pneumonia, borrelia burgdorferi, and beta-hemolytic Streptococcus [4]. In 2020, the global pandemic associated with severe acute respiratory syndrome coronavirus 2?(SARS-CoV-2) infection resulted in multiple reports of associated ADEM [5, 6]. Given that numerous infectious organisms can trigger ADEM, alternative mechanisms of pathogenesis may include activation of existing autoreactive lymphocytes through a nonspecific inflammatory process and entry into the CNS by transient breakdown of the bloodCbrain barrier [7]. Prior vaccines that were contaminated with neural tissue, including the Semple rabies vaccine, led to an increased incidence of ADEM [8]. Currently, most evidence suggests no significant association between ADEM and prior immunization [9]. Most historical data, including the incidence of measles following natural infection versus immunization, suggests that the risk of ADEM is many folds higher in the former [10, 11]. Epidemiology ADEM is a rare illness with an incidence of 0.2C0.4 per 100,000 children annually [12, 13]. The most common age of presentation is between 3 and 7 years [14]. There is a slight male predominance but no specific ethnic predilection [15]. In up to 75% of ADEM cases, a febrile upper respiratory or gastrointestinal illness precedes the onset of neurological symptoms [16, 17]. Some studies have reported a seasonal predilection for winter and spring [18]. Clinical Features In the typical presentation of ADEM, MDL-800 neurological symptoms develop 1C2 weeks following an infection and MDL-800 may involve headache, emesis, meningismus, and alterations in MDL-800 behavior and level of alertness. Encephalopathy and multifocal neurological deficits are.