Objectives:
The aim of this study was to assess the Dutch nationwide incidence of myelin oligodendrocyte glycoprotein (MOG)-IgG-associated acquired demyelinating syndromes (ADS) and to describe the ...clinical and serological characteristics of these patients.
Methods:
All serum samples for routine diagnostics from February 2014 to December 2017 were sent to the single central reference laboratory for the full-length MOG-IgG cell-based assay (CBA) in the Netherlands. Clinical data from patients known in our National ADS centre were available.
Results:
A total of 1414 samples of 1277 patients were received; of these, 92 patients (7%) were MOG-IgG-seropositive. The mean incidence was 0.16/100,000 people, with higher seropositivity in children (0.31/100,000) than in adults (0.13/100,000). In MOG-IgG-positive patients at the National ADS centre (61/92, 66%), the most common presenting phenotype is acute disseminated encephalomyelitis (ADEM, 56%) in children and optic neuritis (ON, 44%) in adults. Relapsing disease occurred in 9/34 (26%) children and 11/27 (41%) adults during median follow-up of 27.5 months. Patients were tested MOG-IgG-positive >200 months after the initial attack, suggesting an extended time to first relapse (TTFR). Longitudinal analysis of MOG-IgG (25/61, 41%) showed that 67% of the monophasic patients remain seropositive and 60% in relapsing patients. Majority of seronegative patients had no relapses (89%).
Conclusion:
This nationwide study shows that the overall incidence of MOG-IgG-seropositive disorders is 0.16 per 100,000 people. The distribution over the clinical phenotypes differs between adults and children. Seropositivity can be maintained over years even without clinical activity, while seronegative patients generally had no relapses.
Over the past few years, increasing interest in the role of autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs) as a new candidate biomarker in demyelinating central nervous system ...diseases has arisen. MOG-abs have now consistently been identified in a variety of demyelinating syndromes, with a predominance in paediatric patients. The clinical spectrum of these MOG-ab-associated disorders (MOGAD) is still expanding and differs between paediatric and adult patients. This first part of the Paediatric European Collaborative Consensus emphasises the diversity in clinical phenotypes associated with MOG-abs in paediatric patients and discusses these associated clinical phenotypes in detail. Typical MOGAD presentations consist of demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM) in younger, and optic neuritis (ON) and/or transverse myelitis (TM) in older children. A proportion of patients experience a relapsing disease course, presenting as ADEM followed by one or multiple episode(s) of ON (ADEM-ON), multiphasic disseminated encephalomyelitis (MDEM), relapsing ON (RON) or relapsing neuromyelitis optica spectrum disorders (NMOSD)-like syndromes. More recently, the disease spectrum has been expanded with clinical and radiological phenotypes including encephalitis-like, leukodystrophy-like, and other non-classifiable presentations. This review concludes with recommendations following expert consensus on serologic testing for MOG-abs in paediatric patients, the presence of which has consequences for long-term monitoring, relapse risk, treatments, and for counselling of patient and families. Furthermore, we propose a clinical classification of paediatric MOGAD with clinical definitions and key features. These are operational and need to be tested, however essential for future paediatric MOGAD studies.
•MOGAD include a diverse range of demyelinating and encephalitis-like phenotypes.•ADEM in younger and ON and/or TM in older children comprise >90% of presentations.•All children with demyelination/encephalitis and abnormal MRI need MOG-ab testing.•We recommend an antibody-directed classification: MOG-ab-associated disorders.•Followed by addition of the disease course and clinical phenotype.
In recent years, the understanding about the different clinical phenotypes, diagnostic and prognostic factors of myelin oligodendrocyte glycoprotein-antibody-associated disorders (MOGAD) has ...significantly increased. However, there is still lack of evidence-based treatment protocols for acute attacks and children with a relapsing course of the disease. Currently used acute and maintenance treatment regimens are derived from other demyelinating central nervous system diseases and are mostly centre-specific. Therefore, this part of the Paediatric European Collaborative Consensus attempts to provide recommendations for acute and maintenance therapy based on clinical experience and evidence available from mainly retrospective studies. In the acute attack, intravenous methylprednisolone (IVMP) leads to a favourable outcome in the majority of patients and can be followed by tapering of oral steroids up to a maximum of three months to maintain the benefit of acute treatment by suppressing disease activity. Intravenous immunoglobulins (IVIG) and plasmapheresis constitute second-line therapies in case of insufficient response to IVMP. After a first relapse, maintenance treatment should be started in order to prevent further relapses and the possibility of permanent sequelae. Four first-line therapies consisting of rituximab (RTX), azathioprine, mycophenolate mofetil or monthly IVIG have been identified by the consensus group. In case of further relapses despite maintenance treatment, the consensus group recommends treatment escalation with RTX or IVIG, followed by combining those two, and ultimately adding maintenance oral steroids. Many open questions remain which need to be addressed in further international prospective evaluation of MOGAD treatment. This international collaboration is essential to expand the state of current knowledge.
•Paediatric MOGAD patients typically respond rapidly to IVMP in the acute attack.•IVIG and PLEX are second-line treatment options during acute attack.•Maintenance therapy in paediatric MOGAD should be considered after first relapse.•This E.U. expert consensus recommends IVIG, AZA, MMF or RTX as first-line options.•Escalation of therapy is recommended in case of insufficient treatment response.
Background
Headaches are the most common complaints among pediatric populations. Determining the cause and appropriate treatment for headaches may be challenging and costly, and the impact of ...headaches on the lives of patients and their families is not well understood.
Objective
A systematic literature review was conducted to examine what PROMs are currently used, and to identify quality of life (QoL) concepts important to children suffering from headaches and any known determinants of QoL.
Methods
Embase, Medline, Web of Science, CINAHL, EBSCOhost, PsychINFO, Cochrane CENTRAL and Google Scholar were searched from their inception through to June 2021. Studies investigating QoL, using a validated outcome measure in pediatric patients with headaches, were included. Relevant studies were identified through title and abstract screening and full text review by two independent reviewers. A citation review of included studies was performed. QoL concepts were extracted from the outcome measures that were used in each study to develop a preliminary conceptual model of QoL in children suffering from headaches. Determinants of QoL were also identified and categorized.
Results
A total of 5421 studies were identified in the search. Title and abstract screening resulted in the exclusion of 5006 studies. Among the 415 studies included for full text review, 56 were eligible for final analysis. A citation review resulted in the addition of five studies. Most studies were conducted in high-income countries and included a patient-sample accordingly (
n
= 45 studies). Sixteen different PROMs were identified in the included studies, of which the PedsQL was used the most often (
n
= 38 studies).
The most common health concepts reported were physical functioning (
n
= 113 items), social and psychological wellbeing (
N
= 117,
n
= 91 resp.). Twenty-five unique determinants of QoL were extracted from the included studies.
Conclusion
There is a need for a condition-specific PROM to facilitate the measurement of QoL outcomes in the pediatric headache population. A conceptual model was developed based on the findings from the health concepts. Findings from this review could be used for future qualitative interviews with pediatric patients with headaches to elicit and refine important QoL concepts.
Background:
Radiologically isolated syndrome (RIS) is typified by multiple sclerosis (MS)-like lesions on imaging, without clinical MS symptoms. The prevalence of pediatric RIS is largely unknown.
...Objective:
The objective of the study is to provide an estimated RIS prevalence in a population-based cohort of children.
Methods:
We used data from the Generation R study to identify the childhood RIS prevalence.
Results:
In 5238 participants, only one RIS case was identified (prevalence: 0.02%; 95% confidence interval (CI): 0.00–0.11). During a 62-month follow-up, imaging examinations showed accrual of new focal demyelinating lesions; however, no clinical MS symptoms occurred.
Conclusions:
This study shows that the occurrence of RIS in children from the general population is rare.
Background: Acute disseminated encephalomyelitis (ADEM) affects children more frequently than adults. Current studies investigating ADEM in different age groups are difficult to compare.
Objective: ...To investigate whether the clinical presentation, outcome and disease course of ADEM differ between adults and children.
Methods: Disease characteristics of 25 adults and 92 children suffering from ADEM between 1988 and 2008 were compared.
Results: The most common presenting symptoms of ADEM in both groups were pyramidal signs and encephalopathy. Ataxia occurred more frequently in children (p = 0.002). In general, MRI showed ill-defined and large white matter lesions in both groups, whereas periventricular lesions were more prevalent in adults (p = 0.001). In adults, duration of hospitalization was longer (p = 0.002) and intensive care unit (ICU) admission was more frequently required (p = 0.043). Three adults (12%) and one child (1%) died (p = 0.030). Fewer adults had complete motor recovery after their first clinical event (p < 0.001). In 73 patients follow-up time was ≥ 2 years and most of these patients remained monophasic. Although relapses after ADEM can occur, only one adult (5%) and five children (6%) converted to MS.
Conclusions: The clinical presentations in children and adults share similarities, but the disease course and outcome of ADEM is more severe in adults with respect to hospitalization, ICU admission, recovery and mortality.
Background
Disease activity in patients with multiple sclerosis (MS) is suppressed during pregnancy, whereas attack frequency increases after delivery. It is yet unclear, which immuno – ...endocrinological processes mediate these disease fluctuations. Leptin has been identified as a hormone that can influence inflammatory activity.
Objective
The aim of this study was to investigate whether pregnancy-induced fluctuations of serum leptin levels differed between patients with MS and controls and whether serum leptin levels correlate with periods of enhanced and diminished disease activity.
Methods
Women with MS and healthy women were prospectively followed during and after pregnancy. The MS group could be studied already at a timepoint before pregnancy. Serum leptin and soluble leptin receptor (SLR) levels were measured using enzyme-linked immunosorbent assay.
Results
Pre-pregnancy serum leptin levels were (mean ± SD) 22.9 ± 12.8 ng/ml in the MS group. These levels increased in the third trimester to 28.5 ± 15.0 ng/ml (P = 0.007). The third trimester serum leptin levels in healthy women were comparable, 29.4 ± 19.0 ng/ml. Serum leptin levels after delivery dropped to 18.5 ± 12.8 ng/ml in women with MS (P < 0.001) and to a lesser extend (22.0 ± 17.5 ng/ml) in healthy women (P = 0.04). SLR levels showed the same pattern. Remarkably, women with the highest relative decrease in serum leptin levels after delivery had more often a postpartum relapse (P = 0.008).
Conclusion
In women with MS, leptin increased during late pregnancy. A postdelivery drop in leptin levels was observed in both the MS and control group. The postdelivery drop was associated with the occurrence of postpartum relapse.
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