We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

BackgroundBurden of headache has been assessed in adults in countries worldwide, and is high, but data for children and adolescents are sparse. The objectives of this study were o develop a questionnaire and methodology for the global estimation of burden of headache in children and adolescents, to test these in use and to present preliminary data.MethodsWe designed structured questionnaires for mediated-group self-administration in schools by children aged 6-11 years and adolescents aged 12-17 years. In two pilot studies, we offered the questionnaires to pupils in Vienna and Istanbul. We performed face-to-face interviews in a randomly selected subsample of 199 pupils to validate the headache diagnostic questions.ResultsData were collected from 1,202 pupils (mean 13.9 ± 2.4 years; 621 female, 581 male). The participation rate was 81.1% in Istanbul, 67.2% in Vienna. The questionnaire proved acceptable: ≤5% of participants disagreed partially or totally with its length, comprehensibility or simplicity. The sensitivity, specificity, positive and negative predictive values ranged between 0.71 and 0.76 for migraine and between 0.61 and 0.85 for tension-type headache (TTH). Cronbach’s alpha was 0.83. The 1-year prevalence of headache was 89.3%, of migraine 39.3% and of TTH 37.9%. The prevalence of headache on ≥15 days/month was 4.5%. One fifth (20.7%) of pupils with headache lost ≥1 day of school during the preceding 4 weeks and nearly half (48.8%) reported ≥1 day when they could not do activities they had wanted to. The vast majority of pupils with headache experienced difficulties in coping with headache and in concentrating during headache. Quality of life was poorer in pupils with headache than in those without.ConclusionThese pilot studies demonstrate the usefulness of the questionnaires and feasibility of the methodology for assessing the global burden of headache in children and adolescents, and predict substantial impact of headache in these age groups.

Objective We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5‐year risk for evolution from radiologically isolated syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10‐year, multinational, retrospectively identified RIS dataset. Methods RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models. Results Additional follow‐up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11–74 years), with a median clinical follow‐up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium‐enhanced lesions during follow‐up was also associated with the risk of a seminal event. The reason for MRI and gadolinium‐enhancing lesions at baseline did not influence the risk of a subsequent clinical event. Interpretation Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407–417.

BackgroundHeadache is a leading disabler in adults worldwide. In children and adolescents, the same may be true but the evidence is much poorer. It is notable that published epidemiological studies of these age groups have largely ignored headaches not fulfilling any specific set of ICHD criteria, although such headaches appear to be common. A new approach to these is needed: here we introduce, and investigate, a diagnostic category termed “undifferentiated headache” (UdH), defined in young people as recurrent mild-intensity headache of < 1 h’s duration.MethodsWe conducted a nationwide cross-sectional survey in 31 schools in six regions of Turkey selected by mixed convenience-based and purposive modified cluster-sampling. A validated, standardised self-completed structured questionnaire was administered by a physician-investigator to entire classes of pupils aged 6–17 years.ResultsOf the identified sample of 7889 pupils, 7088 (89.8%) participated. The 1-year prevalence of UdH was 29.2%, of migraine (definite and probable) 26.7%, and of tension-type headache (TTH) (definite and probable) 12.9%. UdH differed with respect to almost all headache features and associated symptoms from both migraine and TTH. Burden of headache and use of acute medication were lower in UdH than in migraine and TTH. Headache yesterday was less common in UdH than migraine (OR 0.32; 95% CI 0.28–0.37) and TTH (OR 0.64; 95% CI 0.56–0.77). Quality of life (QoL) was better in UdH (33.6 ± 5.2) than in migraine (30.3 ± 5.6; p < 0.001) and TTH (32.4 ± 5.3; p < 0.001), but worse than in pupils without headache (35.7 ± 4.7; p < 0.001).ConclusionsThis large nationwide study in Turkey of pupils aged 6–17 years has shown that many children and adolescents have a headache type that does not conform to existing accepted diagnostic criteria. This new diagnostic category of presumably still-evolving headache (undifferentiated headache) is common. UdH differs in almost all measurable respects from both migraine and TTH. Although characterised by mild headaches lasting < 1 h, UdH is associated with significant adverse impact on QoL. Longitudinal cohort studies are needed to evaluate the prognosis of UdH but, meanwhile, recognition of UdH and its distinction from migraine and TTH has implications for epidemiological studies, public-health policy and routine clinical practice.

Recent laboratory and clinical findings include the discovery of antibodies to human and mouse neuro-fibrils showing cross-reactivity with Streptococcus spp. and Mycobacterium tuberculosis heat shock proteins (HSP) in NBS. Diagnostically, two distinct magnetic resonance imaging (MRI) patterns of spinal cord involvement have been observed: (a) "Bagel sign" and (b) "motor neuron" patterns. Therapeutic studies have shown that infliximab effectively prevents further relapses and stabilizes the symptoms of patients experiencing ongoing clinical relapses while being treated with single or multiple immunosuppressant drugs. Primary neurological involvement referred to as NBS. The majority of patients with NBS present with parenchymal involvement that commonly affects the brain stem-diencephalic region. Headache, dysarthria, ataxia, and hemiparesis are the main clinical features of NBS.