IMPORTANCE Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of demyelinating disorders in adults and children. Current therapeutic strategies are largely center specific, and no treatments have been formally evaluated. OBJECTIVE To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab-associated disease.

IMPORTANCE In 2017, the International Panel on Diagnosis of Multiple Sclerosis revised the McDonald 2010 criteria for the diagnosis of multiple sclerosis (MS). The new criteria are easier to apply and could lead to more and earlier diagnoses. It is important to validate these criteria globally for their accuracy in clinical practice. OBJECTIVE To evaluate the diagnostic accuracy of the 2017 criteria vs the 2010 criteria in prediction of clinically definite MS in patients with a typical clinically isolated syndrome (CIS). DESIGN, SETTING AND PATIENTS A total of 251 patients at Erasmus MC, Rotterdam, the Netherlands, in collaboration with several regional hospitals, fulfilled the inclusion criteria. Thirteen patients received another diagnosis early in the diagnostic process and therefore were excluded from the analyses. Nine patients with CIS declined to participate in the study. This left 229 patients who were included between March 2006 and August 2016 in this prospective CIS cohort. Patients underwent a baseline magnetic resonance imaging scan within 3 months after onset of symptoms and, if clinically required, a lumbar puncture was performed. Data were analyzed between December 2017 and January 2018. MAIN OUTCOMES AND MEASURES Sensitivity, specificity, accuracy, and positive and negative predictive value were calculated after 1, 3, and 5 years for the 2017 vs the 2010 criteria. RESULTS Among the 229 patients with CIS, 167 were women (73%), and the mean (SD) age was 33.5 (8.2) years. One hundred thirteen patients (49%) were diagnosed as having CDMS during a mean (SD) follow-up time of 65.3 (30.9) months. Sensitivity for the 2017 criteria was higher than for the 2010 criteria (68%; 95% CI, 57%-77% vs 36%; 95% CI, 27%-47%; P < .001), but specificity was lower (61%; 95% CI, 50%-71% vs 85%; 95% CI, 76%-92%; P < .001). Using the 2017 criteria, more MS diagnoses could be made at baseline (n = 97 [54%]; 95% CI, 47%-61% vs n = 46 [26%]; 95% CI, 20%-32%; P < .001). In the group with at least 5 years of follow-up, 33% of patients who were diagnosed as having MS using the 2017 criteria did not experience a second attack during follow-up vs 23% when using the 2010 criteria. CONCLUSIONS AND RELEVANCE The 2017 revised McDonald criteria are associated with greater sensitivity but less specificity for a second attack than the previous 2010 criteria. The tradeoff is that it leads to a higher number of MS diagnoses in patients with a less active disease course.

IntroductionAcquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands.MethodsChildren < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments.ResultsBetween 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%).ConclusionThe reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted.

Our results support a change of practice wherein a lumbar puncture can be withheld in patients with a head CT scan performed <6 hours after headache onset and reported negative for the presence of SAH by a staff radiologist in the described nonacademic setting.

ObjectiveTo investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases.MethodsBlood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG–seropositive and 42 AQP4-IgG–seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors.ResultsNo significant HLA association was found in MOG-IgG–seropositive patients. The AQP4-IgG–seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707–5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513–8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495–5.042, pc = 0.0199) compared with controls.ConclusionsThe present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG–positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG–positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders.

ObjectiveTo explore the correlation between serum and CSF neurofilament light chain (NfL) and the association of NfL levels and future disease activity in pediatric patients with a first attack of acquired demyelinating syndromes (ADS).MethodsIn total, 102 children <18 years with a first attack of CNS demyelination and 23 age-matched controls were included. Clinically definite multiple sclerosis (CDMS) was set as an endpoint for analysis. CSF NfL was tested by the commercially available ELISA (UmanDiagnostics); serum NfL (sNfL) was tested with a Simoa assay. Hazard ratios (HR) were calculated with Cox regression analysis.ResultsOf the 102 patients, 47 (46%) were tested for CSF NfL. CSF and serum NfL correlated significantly in the total group (ρ 0.532, p < 0.001) and even more significantly in the subgroup of patients with future CDMS diagnosis (ρ 0.773, p < 0.001). sNfL was higher in patients than in controls (geometric mean 6.1 pg/mL, p < 0.001), and was highest in ADS presenting with encephalopathy (acute disseminated encephalomyelitis, n = 28, 100.4 pg/mL), followed by patients without encephalopathy (ADS−) with future CDMS diagnosis (n = 40, 32.5 pg/mL), and ADS− who remained monophasic (n = 34, 17.6 pg/mL). sNfL levels higher than a median of 26.7 pg/mL at baseline are associated with a shorter time to CDMS diagnosis in ADS− (p = 0.045). HR for CDMS diagnosis was 1.09 for each 10 pg/mL increase of sNfL, after correction for age, oligoclonal bands, and MRI measures (p = 0.012).ConclusionThe significant correlation between CSF and serum NfL strengthens its reliability as a peripheral marker of neuroaxonal damage. Higher sNfL levels at baseline were associated with higher probability of future CDMS diagnosis in ADS−.

Background and Objective:Fatigue and physical impairments are a major concern in children with multiple sclerosis (MS) and after acute disseminated encephalomyelitis (post-ADEM). We here aimed to evaluate the interaction between fatigue, exercise capacity, motor performance, neurological status, and quality of life (HRQoL).Methods:In this cross-sectional study, data of 38 children (MS n = 22, post-ADEM n = 16), aged 4–17 years attending our national pediatric MS center, were studied. Fatigue was measured with the Pediatric Quality of Life Multidimensional Fatigue Scale, exercise capacity with the Bruce Protocol, motor performance with the Movement Assessment Battery for Children second edition, HRQoL with the Pediatric Quality of Life Questionnaire, and extent of disability with the Expanded Disability Status Scale (EDSS).Results:Children with MS and post-ADEM experienced more fatigue (p < 0.001), reduced exercise capacity (p < 0.001), and impaired motor performance (p < 0.001), despite low scores on the EDSS. Fatigue, but not the other parameters, was significantly correlated with HRQoL. Fatigue was not correlated with exercise capacity.Conclusion:We confirm the major impact of fatigue on quality of life in children with MS and post-ADEM. Fatigue was not explained by reduced exercise capacity or impaired motor performance. An important finding for clinical practice is that the low EDSS score did not reflect the poor physical functioning.

ObjectiveTo compare the diagnostic accuracy of the McDonald 2017 vs the McDonald 2010 criteria to predict a second attack of MS (clinically definite MS [CDMS]) at the first attack of acquired demyelinating syndromes (ADS).MethodsOne hundred sixty-four children (aged <18 years) with an incident attack of ADS were included in a prospective multicenter study between June 2006 and December 2016. Brain (and spinal if available) MRI was performed ≤3 months after symptom onset. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were compared at baseline between the 2010 and 2017 criteria.ResultsAmong the 164 patients, 110 patients (67%) presented without encephalopathy (ADS–, female 63%; median age 14.8 years, IQR 11.3–16.1years) and 54 (33%) with encephalopathy (acute disseminated encephalomyelitis [ADEM], female 52%; median age 4.0 years, IQR 2.6–6.1 years). Of the 110 ADS– patients, 52 (47%) were diagnosed with CDMS within a median follow-up of 4.5 years (IQR 2.6–6.7 years). The sensitivity was higher for the 2017 criteria than for the 2010 criteria (83%; 95% CI 67–92, vs 49%; 95% CI 33–65; p < 0.001), but the specificity was lower (73%; 95% CI 59–84 vs 87%; 95% CI 74–94, p = 0.02). At baseline, 48 patients fulfilled the 2017 criteria compared with 27 patients when using the 2010 criteria. The results for children aged <12 years without encephalopathy were similar. In patients with ADEM, 8% fulfilled the 2010 criteria and 10% the 2017 criteria at baseline but no patient fulfilled the criteria for CDMS.ConclusionsThe McDonald 2017 criteria are more sensitive than the McDonald 2010 criteria for predicting CDMS at baseline. These criteria can also be applied in children aged <12 years without encephalopathy but not in children with ADEM.Classification of evidenceThis study provides Class II evidence that in children with ADS, the 2017 McDonald criteria are more sensitive but less specific than the 2010 McDonald criteria for predicting CDMS.