Pediatric Acute Disseminated Encephalomyelitis Research Articles

Evaluating Therapeutic Plasma Exchange in Pediatric Acute Disseminated Encephalomyelitis: A Comprehensive Review.

Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune disorder characterized by brain and spinal cord inflammation. In pediatric patients, ADEM presents unique challenges due to its potential for rapid progression and long-term neurological sequelae. Therapeutic plasma exchange (TPE) has emerged as a potential treatment option by targeting the underlying autoimmune process and modulating the inflammatory response. This comprehensive review evaluates the role of TPE in pediatric ADEM, synthesizing evidence from clinical studies and providing insights into its efficacy, safety, and potential benefits. The review highlights the variability in TPE efficacy based on disease severity and patient-specific factors. Implications for clinical practice include considering TPE as a therapeutic option, particularly in severe or refractory cases, and emphasizing the importance of early intervention. Recommendations for future research include long-term prospective studies, comparative effectiveness trials, and efforts to standardize TPE protocols. Overall, continued investigation and innovation in managing pediatric ADEM are essential for improving outcomes and quality of life for affected children and their families.

Multimodal evoked potentials are useful for the diagnosis of pediatric acute disseminated encephalomyelitis.

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.

Myelin oligodendrocyte glycoprotein antibody‐associated disorders: An overview

AbstractIn recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD‐specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders.

Clinical, radiological, therapeutic and prognostic differences between MOG-seropositive and MOG-seronegative pediatric acute disseminated encephalomyelitis patients: a retrospective cohort study.

This study aimed to compare the clinical, radiological, therapeutic, and prognostic differences between pediatric patients showing acute disseminated encephalomyelitis (ADEM) with and without myelin oligodendrocyte glycoprotein (MOG) antibodies. We retrospectively collected all available data of children diagnosed with ADEM and tested for serum MOG antibodies at the Children's Hospital of Chongqing Medical University from January 2017 to May 2021. A total of 62 patients were included in our cohort, of which 35 were MOG-seropositive and 27 were MOG-seronegative. MOG-seropositive ADEM children presented with significantly lower rates of seizures (P = 0.038) and cranial nerve (III-XII) palsy (P = 0.003). Isolated leukocytosis in the blood was more common in ADEM children with MOG antibodies (P < 0.001). The two groups showed no significant differences in the distributions and extent of the MRI lesions as well as the appearance of typical/atypical magnetic resonance imaging (MRI) features. MOG-seropositive children were more likely to relapse (P = 0.017) despite having slower oral prednisolone tapering after acute treatments (P = 0.028). In scoring performed on the basis of two neurological function scoring systems, MOG-seropositive children showed milder neurological disability status at onset (P = 0.017 and 0.025, respectively) but showed no difference during follow-up. In summary, the differences in the clinical manifestations and auxiliary examination findings for MOG-seropositive and MOG-seronegative ADEM children lacked significance and specificity, making early identification difficult. MOG-seropositive children were more likely to relapse and showed slower steroid tapering. Moreover, MOG-seronegative children tended to have more severe neurological impairments at onset with no difference during follow-up.

Multiple sclerosis imaging in clinical practice: a European-wide survey of 428 centers and conclusions by the ESNR Working Group.

To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

Detection of myelin oligodendrocyte glycoprotein antibody in pediatric patient with acute disseminated encephalomyelitis: a case report

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is an immunity-mediated central nervous system demyelinating disorder. Myelin Oligodendrocyte Glycoprotein (MOG) examination provides information about a patient's ADEM development status. A positive MOG antibody can signify a first episode or incomplete recovery. This review aims to report a case of a pediatric patient with acute disseminated encephalomyelitis with positive MOG antibody. Case Presentation: We present a 5-year-old girl with symptoms of low-grade fever, encephalopathy, blurred vision, numb and tingling sensations on hands and feet, weakness, unable to walk. Head MRI (Magnetic Resonance Imaging) examination reveals lesions in the bilateral thalamus and white matter of the left parietal lobe. There was also a bilateral thickening of the optic nerves. Blood laboratory examination was relatively normal, and the MOG antibody test was positive. The patient was then treated with corticosteroids for 1 year and had 2 recurrent episodes of attacks. MOG test evaluation was still also positive 6 months after the first attack. After Intravenous immunoglobulin (IVIG) treatment was given, resulting in excellent clinical response and no recurrent attack since then. Conclusions: ADEM cases have a good prognosis and good recovery. IVIG administration, with the help of other supportive therapy, improves recovery in treating pediatric ADEM.

Clinical characteristics and associated factors of pediatric acute disseminated encephalomyelitis patients with MOG antibodies: a retrospective study in Hangzhou, China

BackgroundTo explore the clinical characteristics and related factors of children with acute disseminated encephalomyelitis (ADEM) with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody.MethodsA retrospective study was conducted and enrolled pediatric ADEM patients who underwent serum MOG antibody detection from May 2017 to August 2020. The patients were divided into two groups: MOG- immunoglobulin G (IgG) positive (n = 35) and MOG-IgG negative (n = 50). We analyzed the clinical characteristics of MOG-IgG-positive ADEM pediatric patients and conducted a comparative analysis between the two groups.ResultsThirty-five patients (21 males and 14 females) in the MOG-IgG-positive group with encephalopathy, multifocal neurological symptoms, and typical magnetic resonance imaging (MRI) abnormalities were enrolled. They usually had a favorable outcome, while some suffered from relapse. Compared to the MOG-IgG-negative group, MOG-IgG-positive ADEM patients had a longer disease duration (median: 10 vs. 6 days), more meningeal involvement (31.4% vs. 8%) and frontal lobe involvement (82.8% vs. 68%), higher relapse rates (14.3% vs. 2%), lower serum tumor necrosis factor (1–12.4 pg/ml, median 1.7 vs. 1–34 pg/ml, median 2.2) and interferon-gamma (1–9.4 pg/ml, median 1.3 vs. 1–64 pg/ml, median 3) (P < 0.05, respectively). Multivariate logistic regression analysis showed that the longer disease duration, meningeal involvement and frontal lobe involvement were the correlated factors of patients with ADEM with MOG antibody (P < 0.05).ConclusionsOur findings provide clinical evidence that MOG-IgG positivity is associated with longer disease duration, meningeal involvement, and frontal lobe involvement.

Prognostic relevance of persistence of myelin oligodendrocyte glycoprotein antibody in pediatric acute disseminated encephalomyelitis

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody plays a significant role in demyelination in pediatric acute disseminated encephalomyelitis (ADEM). Aims and Objectives: To assess the prognostic relevance of persistence of MOG antibody in pediatric ADEM. Materials and Methods: A prospective observational study was conducted over a period of 3 years. Data were collected from Department of Pediatrics of a tertiary care hospital in Durgapur. Neurological examination findings, magnetic resonance imaging brain and spinal cord, electroencephalogram findings, and MOG antibody titer were noted. All patients were followed up for 1 year. MOG Antibody titer was repeated after 6 months of the first episode of demyelination. Data gathered from the patients was documented. Data analysis was performed using fisher’s exact test on graph pad 2×2 contingency table. P&lt;0.05 was considered as statistically significant. Results: Fifty-three children were diagnosed with ADEM. Among these, 27 children were MOG antibody-positive (51%). One child expired and five children were lost to follow up. Forty-seven children were followed up for 1 year. MOG antibody titer was sent at the time of diagnosis and 6 months after first episode of demyelination. Persistently positive MOG antibody (positive at 6 months after 1st episode of demyelination) was significantly associated with the development of multiphasic disseminated encephalomyelitis (MDEM) (P&lt;0.0001), epilepsy (P=0.0176), steroid dependency (P&lt;0.0001), persistent gait disturbance (P=0.0026), but not with the development of Multiple Sclerosis (P=1.000). Conclusion: Persistently positive MOG Antibody was significantly associated with development of MDEM, epilepsy, persistent gait disturbance, and steroid dependency.

Constructional apraxia secondary to frontal lobe lesion in pediatric acute disseminated encephalomyelitis

Constructional apraxia secondary to frontal lobe lesion in pediatric acute disseminated encephalomyelitis

Pediatric acute disseminated encephalomyelitis associated with myelin oligodendrocyte glycoprotein antibodies

Introduction. Myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are immunemediated inflammatory conditions of the central nervous system (CNS) with a wide clinical phenotypic variability. In order to further understand the possible phenotype of MOGAD here we report a pediatric case of acute disseminated encephalomyelitis (ADEM) associated with MOG antibodies. Case outline. A previously healthy four-month-old infant presented due to a 1-day history of fever up to 39?C and vomiting. On admission, she was encephalopathic. Repetitive and frequent stereotyped dystonic movements were observed. Cerebrospinal fluid (CSF) examination showed pleocytosis (lymphocytes were predominant) and proteinorachy. CSF culture and virology results were negative. Serum MOG antibodies were positive. A prolonged electroencephalography showed continuous high-amplitude slow rhythmic activity with captured stereotyped movement. Epileptic discharges were not seen. Although magnetic resonance imaging showed signs of acute demyelinating encephalomyelitis, our patient did not have seizures, despite neuroimaging findings of cortical lesions. Acute treatment with the corticosteroids led to excellent response with full recovery. Conclusion. This case emphasizes the inclusion of the MOG antibodies testing in the initial work-up in children presenting with acute encephalopathy associated with demyelinating or encephalitic abnormalities on brain and/or spinal magnetic resonance imaging even when the clinical phenotype is unusual. The prompt diagnosis of MOGAD is relevant for accurate disease monitoring and treatment strategies.

Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that typically presents in childhood and is associated with encephalopathy and multifocal brain lesions. Although ADEM is thought to be a post-infectious disorder, the etiology is still poorly understood. ADEM is often a monophasic disorder, in contrast to other demyelinating disorders such as multiple sclerosis and neuromyelitis optica spectrum disorder. With increasing awareness, understanding, and testing for myelin oligodendrocyte glycoprotein antibodies, this disease is now known to be a cause of pediatric ADEM and also has the potential to be relapsing. Diagnostic evaluation for ADEM involves neuroimaging and laboratory studies to exclude potential infectious, inflammatory, neoplastic, and genetic mimics of ADEM. Acute treatment modalities include high-dose intravenous corticosteroids, therapeutic plasma exchange, and intravenous immunoglobulin. Long-term outcomes for ADEM are generally favorable, but some children have significant morbidity related to the severity of acute illness and/or manifest 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.

Magnetic resonance imaging at baseline and follow-up to differentiate between pediatric monophasic acquired CNS demyelination and MS

BackgroundIt is essential to distinguish acute disseminated encephalomyelitis (ADEM) from MS early. Our aim was to determine MRI features at baseline and follow-up to distinguish pediatric ADEM from MS stratified according to age at onset. MethodsUsing hospital ICD-10 codes for acquired demyelinating syndromes from a nationwide register and subsequent chart review, we identified 52 children (<18 years) with ADEM and 66 children with MS. We undertook a retrospective analysis of MRI scans at onset and at follow-up. The MRI rater was a senior neuroradiologist blinded to clinical characteristics. ResultsAt baseline, children with ADEM had more diffuse poorly demarcated lesions, particularly in the basal ganglia/thalamus (p = 0.001) and cerebellar peduncles (p < 0.0001). Further, longitudinal extensive transverse myelitis was strongly associated with ADEM (p<0.0001). Children with ADEM had fewer contrast-enhancing lesions (p = 0.0004), occipital lesions (p = 0.01), optic nerve lesions (p = 0.01), periventricular lesions, well-defined lesions only (p<0.0001), and fewer fulfilled dissemination in time according to the McDonald 2017 criteria (p = 0.005). On baseline MRI, dissemination in space and time was fulfilled in 17% of children with ADEM and in 34% of children with MS (p = 0.06), and 60% of children with ADEM fulfilled the criterion for dissemination in space. The mean time from baseline MRI to follow-up MRI was 1.0 year for children with ADEM and 2.1 years for children with MS. On follow-up MRI, 85% of children with ADEM had partial or complete T2 lesion resolution, but in the 58% without complete resolution lesions were predominantly frontal. Only 47% of children with MS had partial or complete T2 lesion resolution, and therefore more MRI features differed between children with ADEM and MS on follow-up. MRI had the greatest distinguishing value after age 11 years because MS is exceptional in the first decade of life. ConclusionAge at onset and the timing of MRI in relation to disease onset are critical in the interpretation of MRI to distinguish between ADEM and MS.

Association between acute disseminated encephalomyelitis and thyroid autoimmunity in children

BackgroundAbnormal thyroid peroxidase antibody (TPOAb) levels are observed in various autoimmune diseases. However, the relationship between TPOAb and pediatric acute disseminated encephalomyelitis (PADEM) remains unclear. This study aimed to investigate the positive rate of TPOAb and thyroid dysfunction in children with acute disseminated encephalomyelitis (ADEM) and assess the relationship between TPOAb and clinical features of PADEM. MethodsThis retrospective single-center case-control study was conducted from April 2017 to April 2019. We enrolled 23 children with ADEM and 23 age- and sex-matched healthy controls. Based on whether they were positive for TPOAb, the children with ADEM were allocated either to the TPOAb+ or TPOAb- group. The median follow-up time was 12 months (6–30 months). Observers were blinded to the patient groupings. We compared the clinical and imaging characteristics of the two groups. ResultsAmong the 23 patients with PADEM, 47.8% presented with abnormal TPOAb levels, while there were no TPOAb+ cases in the control group. Among the children with ADEM, there were significantly increased TPOAb positive rates and significantly decreased fT3 levels. TPOAb+ and TPOAb- subgroup analysis revealed significant differences in gait, fever, and total IgG. In the TPOAb+ group, there was a significant decrease in TPOAb levels at 2 weeks after ADEM onset. The follow-up of patients who were TPOAb+ at 3 months after onset showed a gradual decrease in their TPOAb levels back to normal. One patient who presented new nervous system symptoms after over 1 month also showed a simultaneous increase in TPOAb levels. There was a significant negative correlation between Glasgow Coma Scale (GCS) scores and TPOAb levels (p = 0.042, r = -0.892). ConclusionThere was a negative correlation of TPOAb levels with GCS scores. Therefore, TPOAb levels could be used for the prognosis of patients with PADEM. We recommend determining thyroid function when assessing patients with PADEM during follow-up.

School performance and psychiatric morbidity 6 years after pediatric acute disseminated encephalomyelitis: A nationwide population-based cohort study

BackgroundAcute disseminated encephalomyelitis (ADEM) can cause cognitive impairment in children. However, long-term consequences for school performance and psychiatric morbidity have never been characterized. Our aim was to investigate long-term school performance and psychiatric morbidity after pediatric ADEM (<18 years). MethodsWe identified all children with ADEM 2008–2015 in Denmark using hospital diagnostic codes for acquired demyelinating syndromes. We reviewed all medical records to validate ADEM including blinded MRI review. Reference children were the entire pediatric (<18 years) population or randomly sampled sex and age-matched reference children. Outcomes were from nationwide population-based registers on special needs assistance, grade point average, highest completed education, in-hospital psychiatric hospital diagnoses, out-of-hospital psychiatric consultations or psychopharmacological drug prescriptions. Results52 children had ADEM (median onset age: 5.5 years; median age at follow-up end: 13.4 years). Secondary school grade point average was similar among children with ADEM and reference children; however, children with ADEM had increased psychiatric morbidity (hazard ratio = 2.4; 95% confidence interval = 1.2–5.1; p = 0.02), primarily due to increased drug prescriptions for sleep problems and depression. ConclusionChildren with prior ADEM have increased sleep problems and possibly also depression; however, school performance is seemingly unaffected. Clinicians should consider problems with sleep and mood at follow-up.

Incidence of pediatric neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease in Denmark 2008‒2018: A nationwide, population-based cohort study

BackgroundThe incidence of pediatric neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease have not been reported previously. Our aim was to estimate the incidence of pediatric NMOSD and the occurrence of anti-MOG antibody-associated disease in Denmark during 2008–18, and to evaluate the diagnostic usefulness of antibodies against MOG and aquaporin-4 (AQP4) in children <18 years. MethodsWe undertook a nationwide, population-based, multicenter cohort study using data from the Danish National Patient Register, the Danish Multiple Sclerosis Registry, and laboratories providing anti-AQP4 and anti-MOG antibody analyses. Diagnoses were confirmed by review of the medical records, including blinded MRI review in most children with acute disseminated encephalomyelitis (ADEM). ResultsIn children with acquired demyelinating syndromes, anti-AQP4 antibodies were detected in 4% and anti-MOG antibodies in 18%, including in the two children with ADEM who relapsed. We identified four children with NMOSD, equivalent to an incidence of 0.031/100,000 (95% confidence interval = 0.011‒0.082). In anti-MOG antibody-positive children, 32% relapsed during follow-up. ConclusionsPediatric NMOSD and MOG antibody-associated disease are rare, but one-third of anti-MOG-positive children relapsed. In pediatric ADEM, only anti-MOG antibody-positive children relapsed, but the overall risk of relapse after pediatric ADEM was low.

Clinical time course of pediatric acute disseminated encephalomyelitis

The detailed clinical time course in acute disseminated encephalomyelitis (ADEM) from initial symptoms, through exacerbation, to remission has not been widely reported. Hence, this study aimed to investigate the clinical time course of pediatric ADEM. This was a multicenter retrospective study based on registry data from medical chart reviews. The study included children who met the international consensus diagnostic criteria for ADEM. The patients comprised 18 boys and 6 girls, with a mean age of 5.5 ± 3.3 years at onset. From onset, the time until peak neurological symptoms, time until initial improvement, and time until full recovery was 3.1 ± 3.7 days, 6.0 ± 4.5 days, and 26 ± 34 days, respectively. Twenty-three (96%) patients were treated with high-dose methylprednisolone (mPSL) with a mean duration of 4.1 ± 4.0 days from onset. The condition of 15 patients (65%) improved within 3 days of high-dose mPSL initiation, whereas, that of four patients began to improve after >5 days of high-dose mPSL initiation. Only one patient (4%) did not achieve full recovery despite treatment with high-dose mPSL, intravenous immunoglobulin, and plasma exchange. This study presents the detailed clinical time course in pediatric ADEM in Japan. Progression of neurologic deficits typically lasts a few days, with initial improvement in 1 week leading to full recovery within 1 month.

Increased Intracranial Pressure in Acute Disseminated Encephalomyelitis

To assess the intracranial pressure in pediatric acute disseminated encephalomyelitis using spinal tap opening pressure on lumbar puncture, which is routinely performed as part of suspected acute disseminated encephalomyelitis workup. Compared to other cerebrospinal fluid parameters such as cell count, protein concentration, and presence of oligoclonal bands, cerebrospinal fluid opening pressure is infrequently recorded. A retrospective chart review of demographic, clinical, and laboratory data of children diagnosed with acute disseminated encephalomyelitis admitted to a tertiary referral hospital between 2005 and 2016. Of the 36 children diagnosed with acute disseminated encephalomyelitis, 24 had the cerebrospinal fluid opening pressure documented in their records. The mean cerebrospinal fluid opening pressure was 27.6±12.6 cmH2O, range 9-55 cmH2O (95% confidence interval 21.9-33.6). Cerebrospinal fluid opening pressure in the acute disseminated encephalomyelitis group was statistically significantly higher ( P = .0013, 95% confidence interval 4.2-15.0) than the accepted upper limit in this age group (18 cmH2O). In 10 of 24 patients (42%), the opening pressure was above 28 cmH2O. Increased opening pressure was the most frequent cerebrospinal fluid abnormal finding in our cohort, which suggests a potential role of increased intracranial pressure in the acute disseminated encephalomyelitis pathophysiological disease mechanism. In certain cases, the opening pressure value could have monitoring and therapeutic implications, and therefore its measurement is highlighted by this study.

Implications of the International Paediatric Multiple Sclerosis Study Group consensus criteria for paediatric acute disseminated encephalomyelitis: a nationwide validation study.

The International Paediatric Multiple Sclerosis Study Group (IPMSSG) has proposed criteria for acute disseminated encephalomyelitis (ADEM) not evaluated in clinical practice. Our objective was to assess epidemiological implications of the IPMSSG criteria for ADEM in a cohort study using prospectively collected data. We identified all diagnosed cases of ADEM in Denmark between 2008 and 2015 from the Danish National Patient Register by International Classification of Diseases 10 codes assigned to acute demyelinating episodes, and we reviewed all medical records to validate ADEM. We found 52 children up to the age of 18 years with a verified clinical diagnosis of ADEM (incidence rate 0.54/100000 person-years; all had abnormal brain magnetic resonance imaging). Only 18 (35%) fulfilled the IPMSSG criteria regarding encephalopathy and polyfocal neurological deficits. Among all 52 children with ADEM, 33 per cent had clinical sequelae after a median follow-up of 4 years 6 months (range: 10mo-8y 3mo). Surprisingly, none progressed to multiphasic ADEM or multiple sclerosis, but median age at end of follow-up was only 10 years 9 months (range: 2y-24y 3mo). Among 52 children with ADEM, none converted to multiphasic ADEM or multiple sclerosis (median follow-up: 4y 6mo; range: 10mo-8y 3mo). Applying the IPMSSG criteria to all children with a diagnosis of ADEM leaves 65 per cent of the cases without a diagnosis and lowers the incidence rate of paediatric ADEM. The incidence of paediatric acute disseminated encephalomyelitis (ADEM) was 0.54 per 100000 person-years in children younger than 18 years. Only 35 per cent of children with ADEM fulfilled the International Paediatric Study Group consensus criteria. ADEM in clinical practice was primarily based on magnetic resonance imaging findings. Paediatric neurologists diagnosed ADEM in the absence of encephalopathy. None of the children with ADEM progressed to multiple sclerosis/multiphasic ADEM during follow-up.

Paediatric acute disseminated encephalomyelitis followed by optic neuritis: disease course, treatment response and outcome.

Acute disseminated encephalomyelitis followed by optic neuritis (ADEM-ON) is a rare demyelinating syndrome that is different from multiple sclerosis and neuromyelitis optica spectrum disorder. The aim of this study was to describe the disease course, treatment response and outcome of children with ADEM-ON. Children of <18years of age were identified from six countries of the EU Paediatric Demyelinating Disease Consortium. Patients fulfilled the diagnostic criteria for ADEM followed by at least one ON. Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies were tested in all patients. In this study of 17 patients (nine boys) with ADEM-ON, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies were identified in 16 patients. Age at onset was 6.1years (interquartile range, 5.1-9.2years). Twelve patients received oral prednisolone and 10 received maintenance immunosuppression (e.g. azathioprine, intravenous immunoglobulins, Rituximab). During a follow-up of 5.3years (interquartile range, 1.8-10.2years), 54 relapses occurred with a median of 3 relapses per patient (range, 1-9 per patient). Patients relapsed on all treatments but no relapses occurred on a prednisolone dose >10mg/day. Visual and cognitive residual deficits were common in this group. Acute disseminated encephalomyelitis followed by optic neuritis is an anti-MOG antibody-associated relapsing disorder that can have a heterogeneous disease course. Patients were refractory for maintenance immunosuppression and appeared to be corticosteroid-dependent. Further international collaborations are now required to unify guidelines in this difficult-to-manage group of patients.

Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report

BackgroundAnti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein–Barr virus (EBV) infection.Case presentationA 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative.ConclusionsThis case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.