Herpes simplex virus type 2 implicated in a case of acute disseminated encephalomyelitis

We describe the case of a 30-month-old boy who developed acute disseminated encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately died. As far as we know, this is only the second case of HAV-associated ADEM to be reported in the literature. The child was brought to hospital with fever, lethargy and weakness of 2 days duration. He had developed jaundice, abdominal pain and malaise 2 weeks beforehand and these problems had resolved within 2 days. Neurological examination revealed lethargy, generalised weakness and positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of the brain revealed diffuse cerebral oedema and multifocal hyperintensities on T2-weighted images, with most lesions in the white matter of both cerebral hemispheres. The diagnosis of ADEM was established and high-dose steroids and intravenous immunoglobulin were added to the treatment regimen. However, his clinical condition continued to deteriorate and he died on the 20th day in hospital. This case shows that HAV infection can be linked with ADEM. Patients with HAV infection should be examined carefully for central nervous system symptoms during follow-up. Likewise, the possibility of HAV infection should be investigated in cases of ADEM.

Acute Disseminated Encephalomyelitis Presenting as Conversion Disorder

Acute Disseminated Encephalomyelitis Presenting as Conversion Disorder

Case reports have suggested that vaccines may trigger transverse myelitis (TM) or acute disseminated encephalomyelitis (ADEM), but the evidence for a causal association is inconclusive. We analyzed the association of immunization and subsequent development of TM or ADEM. We identified all cases of TM and ADEM in the Vaccine Safety Datalink population. Using a case-centered method, we compared vaccination of each case to vaccination of all matched persons in the study population, who received the same type of vaccine, with respect to whether or not their vaccination occurred during a predetermined exposure interval. We calculated a risk difference (excess risk) of TM and ADEM for each vaccine. Following nearly 64 million vaccine doses, only 7 cases of TM and 8 cases of ADEM were vaccinated during the primary exposure window 5-28 days prior to onset. For TM, there was no statistically significant increased risk of immunization. For ADEM, there was no statistically significant increased risk following any vaccine except for Tdap (adolescent and adult tetanus, reduced diphtheria, acellular pertussis) vaccine. Based on 2 exposed cases, the odds ratio for Tdap exposure 5-28 days prior to ADEM onset was 15.8 (95% confidence interval [CI], 1.2-471.6; P = .04), and the estimated excess risk was 0.385 (95% CI, -.04 to 1.16) cases per million doses. We found no association between TM and prior immunization. There was a possible association of ADEM with Tdap vaccine, but the excess risk is not likely to be more than 1.16 cases of ADEM per million vaccines administered.

Ostre rozsiane zapalenie mózgu i rdzenia kręgowego u dzieci jako następstwo jałowego zapalenia opon mózgowo-rdzeniowych – opis dwóch przypadków

The application of evoked potentials (EPs) to the diagnosis of acute disseminated encephalomyelitis (ADEM ) has not been investigated in detail. The aim of this study, therefore, was to analyze the value of multimodal EPs in the early diagnosis of pediatric ADEM. This was a retrospective study in which we enrolled pediatric ADEM patients and controls (Cs) from neurology units between 2017 and 2021. We measured indices in patients using brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs), and then we analyzed their early diagnostic value in ADEM patients. The mean age of the ADEM group was 6.15 ± 3.28 years (range,1-12 years) and the male/female ratio was 2.1:1 The mean age of the Cs was 5.97 ± 3.40 years (range,1-12 years) and the male/female ratio was 1.3:1. As we used magnetic resonance imaging (MRI) as the diagnostic criterion, the sensitivity, specificity, and accuracy (κ was 0.88) of multimodal EPs were highly consistent with those of MRI; and the validity could be ranked in the following order with respect to the diagnosis of ADEM: multimodal Eps > single SEP > single VEP > single BAEP. Of 34 patients with ADEM, abnormalities in multimodal EPs were 94.12%, while abnormalities in single VEPs, BAEPs and SEPs were 70.59%,64.71%and 85.3%, respectively. We noted significant differences between single VEP/BAEPs and multimodal EPs (χ2 = 6.476/8.995,P = 0.011/0.003). The combined application of multimodal EPs was superior to BAEPs, VEPs, or SEPs alone in detecting the existence of central nerve demyelination, and we hypothesize that these modalities will be applicable in the early diagnosis of ADEM.

Multiple sclerosis vs acute disseminated encephalomyelitis in childhood

We aimed to determine whether acute disseminated encephalomyelitis (ADEM) diagnosis in children is delayed, and if so, to identify the clinical risk factors of delayed diagnosis. Standardised data were collected from children with ADEM from 2003 to 2020. Overall diagnostic delay (time between symptom onset and ADEM diagnosis), physicians’ delay (between the first medical visit and ADEM diagnosis), and patients’ delay (between symptom onset and the first medical visit) were analysed. Thirty ADEM patients were identified, including 16 (54%) with neurological deficits at discharge. Overall, physicians’, and patients’ delays were 9 (interquartile range [IQR] 6–20.5), 5.5 (IQR 3–14), and 4 (IQR 2–8) days, respectively. Overall delay was significantly associated with physicians’ delay, but not with patients’ delay. There were 61 misdiagnoses among 25 (83%) patients, while 5 (17%) were diagnosed correctly at the first visit. The misdiagnoses of common respiratory and gastrointestinal infection and aseptic meningitis were associated with overall and/or physicians’ delay. Later onset of specific neurological features suggestive of ADEM was associated with all three diagnostic delays. A unique diagnostic odyssey exists in ADEM. Several clinical risk factors were associated with the diagnostic delay.

Objective To study the clinical features and treatment of acute disseminated encephalomyelitis (ADEM). Methods All patients admitted with ADEM during May 1990 to Dec 2010 were included in the study. Clinical data of 12 cases with ADEM were reviewed and analysed. The diagnosis of ADEM was made based on the clinical presentation, suggestive MRI and auxiliary examination findings. All patients were treated with intravenous steroids or immunoglobulins (IVIg). Results The sample consisted of 10 men and 2 women. The oldest patient was 69 years old and the youngest was 6 years old. Six patients had definite upper respiratory tract infection preceded the onset of neurological symptoms, 3 patients had non⁃specific fever, 1 patient had measles vaccination, 1 patient had measles prior to the onset 4 months ago. No preceding illness and vaccination occurred in 1 patient. The common presenting symptoms were fever, nausea, vomiting, headache. Neurological manifestations included cranial nerve involvement (the abducent nerve was the most common cranial nerve involved), paralysis (include hemiplegia, quadriplegia, paraplegia), altered sensorium, bladder involvement (both incontinence and retention), meningeal irrigation sign and conscious disturbance. Conclusion Despite the serious manifestation, ADEM in patient has good immediate outcome. Early diagnosis and treatment should be emphasized. DOI：10.3969/j.issn.1672⁃6731.2012.02.015

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating CNS disorder with predilection to early childhood. ADEM is generally considered a monophasic disease. However, recurrent ADEM has been described and defined as multiphasic disseminated encephalomyelitis. ADEM often occurs postinfectiously, although a causal relationship has never been established. ADEM and multiple sclerosis are currently viewed as distinct entities, generally distinguishable even at disease onset. However, pathologic studies have demonstrated transitional cases of yet unclear significance. ADEM is clinically defined by acute polyfocal neurologic deficits including encephalopathy. MRI typically demonstrates reversible, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalami and basal ganglia. CSF analysis may reveal a mild pleocytosis and elevated protein, but is generally negative for intrathecal oligoclonal immunoglobulin G synthesis. In the absence of a specific diagnostic test, ADEM is considered a diagnosis of exclusion, and ADEM mimics, especially those requiring a different treatment approach, have to be carefully ruled out. The role of biomarkers, including autoantibodies like anti-myelin oligodendrocyte glycoprotein, in the pathogenesis and diagnosis of ADEM is currently under debate. Based on the presumed autoimmune etiology of ADEM, the current treatment approach consists of early immunotherapy. Outcome of ADEM in pediatric patients is generally favorable, but cognitive deficits have been reported even in the absence of other neurologic sequelae. This review summarizes the current knowledge on epidemiology, pathology, clinical presentation, neuroimaging features, CSF findings, differential diagnosis, therapy, and outcome, with a focus on recent advances and controversies.

New-Onset Right-Sided Weakness and Unsteady Gait in a 10-year-old Boy.

IntroductionSince the beginning, there has been enough evidence about the multi-systematic involvement of the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent observations have revealed that, together with others, typical neurological manifestations are also associated with COVID-19 infection. In the first 2 years, children accounted for a few percent of cases, but with the emergence of the Omicron variant, the number of cases in the pediatric population has increased. It has been described that ~5% of the affected population suffered from severe neurological complications, such as seizure, coma, encephalitis, demyelinating disorders, and aseptic meningitis. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system. Typically, it presents in childhood and occurs 1 or 2 weeks after infection or vaccination.Case presentationWe present the case of a 12-year-old boy who developed ADEM, 10 days after an asymptomatic SARS-CoV-2 infection. Neurological symptoms began with headache, fever, irritability, paraplegia, and loss of sensitivity from the T1 level. The diagnosis of ADEM was confirmed by the typical signs found on brain MRI, whereas spinal cord MRI showed signs of transverse myelitis. The cerebrospinal fluid (CSF) testing excluded infections and did not reveal oligoclonal antibody bands (anti-MOG-negative and anti-AQP-negative). High-dose steroids (30 mg/kg/day) and IVIG (2 g/kg) were administered to the patient without any clinical improvement. The patient received a cycle of plasma exchange therapy, followed by rituximab infusion, with partial improvement. After 3 months, the magnetic resonance imaging (MRI) results demonstrated radiological improvement in accordance with the ADEM diagnosis.ConclusionThis clinical case confirms that SARS-CoV-2 infections are increasingly implicated in severe neurological consequences in both adult and pediatric patients. While the most frequent complications that were reported in children included headache, altered mental status, and encephalopathy, ~5% of the individuals suffered from severe neurological complications, leading to lifelong sequelae. All physicians must be aware of these data and detect neurological signs of severe (or not) complications that require a specific follow-up and treatment.

Acute disseminated encephalomyelitis is a rare inflammatory demyelinating multifocal disease of the central nervous system that typically occurs in children following vaccination or exanthematous viral infections and conveys an elevated risk of neurological sequelae unless promptly recognized and treated. We describe an adult case of acute disseminated encephalomyelitis following vaccination against Mumps, Measles and Rubella, presenting with fever and progressive neurological deficits which improved under systemic corticosteroid therapy. Considering the ongoing public debate regarding universal vaccination and the surge of previously controlled infectious diseases, we aim not only to underline the need for a rigorous assessment of vaccination safety on adult patients in order to prevent misguidance of public opinion, but also to alert clinicians for an early diagnosis of acute disseminated encephalomyelitis in these patients, the incidence of which we speculate may be rising.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating central nervous system (CNS) disorder with predilection to early childhood. ADEM is generally considered a monophasic disease. ADEM often occurs postinfectiously although a casual relationship has never been established. ADEM is clinically defined by acute polyfocal neurologic deficits including encephalopathy. MRI typically demonstrates reversible, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalamy and basal ganglia. CSF analysis may reveal a mild pleocytosis and elevated protein, but is generally negative for intrathecal oligoclonal immunoglobulin G synthesis. In the absence of a specific diagnostic test, ADEM is considered a diagnosis of exclusion. The role of biomarkers, including autoantibodies like antimyelinoligodendrocyte glycoprotein, in the pathogenesis and diagnosis of ADEM is currently under debate. Based on the presumed autoimmune etiology of ADEM, the current treatment approach consists of early immunotherapy. Outcome of ADEM in pediatric patients is generally favorable, but cognitive deficits have been reported even in the absence of other neurologic sequelae. This review summarizes the current knowledge on epidemiology, pathology, clinical presentation, neuroimaging features CFS findings, differential diagnosis, therapy, and outcome, with focus on recent advances and controversies.

Background: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS), characterized by new onset polyfocal neurologic symptoms with encephalopathy and multifocal demyelination, typically occurring in early childhood. The initial diagnosis of ADEM can be challenging, as up to 20% of children with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) are initially diagnosed with ADEM. Objective:To describe characteristics of patients with ADEM vs. recurrent demyelinating syndromes (MS, NMOSD, other) at the time of initial presentation and identify features at disease onset of presentations consistent with ADEM associated with monophasic demyelinating disease. Methods: This is a multicenter observational cohort study of children with a demyelinating disease diagnosis of ADEM, multiphasic ADEM, MS, and NMOSD who were followed at 12 regional pediatric MS referral centers in the US Network of Pediatric MS Centers. Descriptive statistics were used to report patient characteristics, clinical/imaging presenting features and subsequent outcomes. Logistic regression was used to predict features associated with a monophasic course. Results: As of July 2019, 872 pediatric patients with a final diagnosis of ADEM (n=89), MS (n= 664) or NMOSD (n=119) were identified. The mean +/- standard deviation follow-up for all patients was 5·7 +/- 3·1 years. ADEM patients were the youngest with mean age at first event 5·4 +/- 3·7 years (p < 0.001) and male predominance (62%) (p < 0·001). Severe clinical symptoms at onset were more frequent in ADEM (55% vs. 35% NMOSD and 15% MS, p < 0·001). After 2 years of follow-up, 78% (93/119) of patients initially diagnosed with ADEM retained this diagnosis (ADEM to ADEM), while 9·2% were later reclassified as MS, 3·3% as NMOSD and 7·5% as demyelinating disease not otherwise specified (DDNOS). In univariable logistic regression, younger age at first event was associated with retaining ADEM diagnosis, while presentation with optic neuritis and gadolinium enhancement on brain MRI were associated with ADEM reclassification to MS, NMOSD, or DDNOS at 2 years of follow-up. In multivariable analysis, older age at first event (OR 1·16 [95% CI 1·00 – 1·33] for 1-year increase, p = 0·04), presenting with optic neuritis (OR 15·31 [95% CI 3·27 – 71·66], p <0·001) and presence of gadolinium enhancement on brain MRI at onset (OR 6·80 [95% CI 2·03 – 22·78], p = 0·0019) were associated with reclassification of ADEM to MS, NMOSD or DDNOS within 2 years. Conclusion: Children who remain classified as ADEM vs. those who are reclassified as other demyelinating disorders are younger at onset, and less likely to have optic neuritis or gadolinium-enhancing lesions at disease onset. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The ethics committees of participating institutions approved this study. Parents and participants signed consent forms and assent forms when required by each center’s institutional review board prior to enrollment.