Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological ...characterisation of this subgroup is lacking.
To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies.
Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed.
MOG antibodies (median 1:2560; range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children with MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well-defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038).
Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies.
New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet ...to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first- and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics.
Aim
To monitor the trends in prevalence of cerebral palsy (CP) by birthweight in Europe, 1980 to 2003.
Method
Data were collated from 20 population‐based registers contributing to the Surveillance of ...Cerebral Palsy in Europe database. Trend analyses were conducted in four birthweight groups: <1000g (extremely low birthweight ELBW); 1000 to 1499g (very low birthweight VLBW); 1500 to 2499g (moderately low birthweight MLBW); and >2499g (normal birthweight NBW).
Results
The overall prevalence of CP decreased from 1.90 to 1.77 per 1000 live births, p<0.001, with a mean annual fall of 0.7% (95% confidence interval CI −0.3% to −1.0%). Prevalence in NBW children showed a non‐significant trend from 1.17 to 0.89 per 1000 live births (p=0.22). Prevalence in MLBW children decreased from 8.5 to 6.2 per 1000 live births (p<0.001), but not linearly. Prevalence in VLBW children also declined from 70.9 to 35.9 per 1000 live births (p<0.001) with a mean annual fall of 3.4% (95% CI −2.4% to −4.3%). Prevalence in ELBW children remained stable, at a mean rate of 42.4 per 1000 live births.
Interpretation
The decline in prevalence of CP in children of VLBW continues, and confirms that previously reported. For the first time, there is also a significant decline among those of MLBW, resulting in a significant overall decrease in the prevalence of CP.
What this paper adds
Cerebral palsy (CP) prevalence in children born very low birthweight in 1980 to 2003 further decreased compared to 1980 to 1996.
CP prevalence in children born moderately low birthweight has significantly decreased.
The result is a significant decrease in the overall CP prevalence.
This article is commented on by Smithers‐Sheedy on page 14 of this issue.
We investigate common pathophysiology in paediatric and adult multiple sclerosis (MS) by comparison of cerebrospinal fluid (CSF) data. We compared cerebrospinal fluid (CSF) data from eight patient ...groups with onset of MS at 7 to 29 years (n = 184). A new statistics program allows sensitive detection, quantifies the mean amount of intrathecal Ig synthesis in groups based on the 96% reference range of 4100 non-inflammatory controls, corrects for age-related increase of blood-derived albumin and immunoglobulins in CSF, and presents graphical data interpretation in Reibergrams. Already at onset of MS before puberty (≤10 years) the frequency of intrathecal IgG synthesis (oligoclonal IgG) was 100% like in adults with 98%, but the amount of intrathecal IgG increases twofold during puberty. Intrathecal IgM synthesis is most frequent before and during puberty (in 57—67% of patients) compared with 41% in adults. The amount of intrathecal IgM synthesis before puberty is only 30% of that in adults. IgG and IgM Index are biased evaluations not suitable for characterizing age-related dynamics. A twofold age-related increase of the albumin quotient, QAlb, as a measure of the blood—CSF barrier function, represents normal physiological growth. Cell counts in CSF are low. The pre-puberty gender ratio is about 1:1. Intrathecal antibodies against measles, rubella and/or varicella zoster virus are detected in 73% of patients before puberty compared with 89% of adults. Individual paediatric patients (n = 17), with sequential punctures over 2—5 years, show constant quantities of intrathecal IgM and specific antibodies. In conclusion, paediatric MS already at first clinical manifestation shows the complete, neuroimmunological data pattern in CSF, i.e. inflammatory signs are not gradually evolving. Paediatric and adult MS differ quantitatively but not qualitatively in neuroimmunological patterns which does not allow for discrimination between ‘early’ and ‘late’ onset MS. CSF analysis may help to discriminate between acute and mono-symptomatic chronic inflammatory disease already at earliest clinical manifestation.
Aim
To develop and evaluate a classification system for magnetic resonance imaging (MRI) findings of children with cerebral palsy (CP) that can be used in CP registers.
Method
The classification ...system was based on pathogenic patterns occurring in different periods of brain development. The MRI classification system (MRICS) consists of five main groups: maldevelopments, predominant white matter injury, predominant grey matter injury, miscellaneous, and normal findings. A detailed manual for the descriptions of these patterns was developed, including test cases (www.scpenetwork.eu/en/my-scpe/rtm/neuroimaging/cp-neuroimaging/). A literature review was performed and MRICS was compared with other classification systems. An exercise was carried out to check applicability and interrater reliability. Professionals working with children with CP or in CP registers were invited to participate in the exercise and chose to classify either 18 MRIs or MRI reports of children with CP.
Results
Classification systems in the literature were compatible with MRICS and harmonization possible. Interrater reliability was found to be good overall (k=0.69; 0.54–0.82) among the 41 participants and very good (k=0.81; 0.74–0.92) using the classification based on imaging reports.
Interpretation
Surveillance of Cerebral Palsy in Europe (SCPE) proposes the MRICS as a reliable tool. Together with its manual it is simple to apply for CP registers.
What this paper adds
MRI Classification System (MRICS) is a mainly qualitative classification system for children with cerebral palsy (CP).
MRICS describes pathogenic neuroimaging patterns related to timing of brain compromise.
The classification system proved to be reliable and easy to use for CP registers.
MRICS was compared with other classification systems and harmonization was feasible.
This article is commented on by Ditchfield on page 9 of this issue.
Video Podcast: https://youtu.be/-vF7sfjhJlI
To study the longitudinal dynamics of anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies in childhood demyelinating diseases.
We addressed the kinetics of anti-MOG immunoglobulins in a ...prospective study comprising 77 pediatric patients. This was supplemented by a cross-sectional study analyzing 126 pediatric patients with acute demyelination and 62 adult patients with multiple sclerosis (MS). MOG-transfected cells were used for detection of antibodies by flow cytometry.
Twenty-five children who were anti-MOG immunoglobulin (Ig) positive at disease onset were followed for up to 5 years. Anti-MOG antibodies rapidly and continuously declined in all 16 monophasic patients with acute disseminated encephalomyelitis and in one patient with clinically isolated syndrome. In contrast, in 6 of 8 patients (75%) eventually diagnosed with childhood MS, the antibodies to MOG persisted with fluctuations showing a second increase during an observation period of up to 5 years. Antibodies to MOG were mainly IgG 1 and their binding was largely blocked by pathogenic anti-MOG antibodies derived from a spontaneous animal model of autoimmune encephalitis. The cross-sectional part of our study elaborated that anti-MOG Ig was present in about 25% of children with acute demyelination, but in none of the pediatric or adult controls. Sera from 4/62 (6%) adult patients with MS had anti-MOG IgG at low levels.
The persistence or disappearance of antibodies to MOG may have prognostic relevance for acute childhood demyelination.
Background
Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MS
ped
) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD
ped
) in ...children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode.
Methods
Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls.
Results
Thirteen MOGAD
ped
(10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MS
ped
(14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGAD
ped
compared to MS
ped
(pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm,
p
< 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm
3
,
p
< 0.001). Neither other macular layers nor P100 latency differed. MOGAD
ped
developed global atrophy affecting all peripapillary segments, while MS
ped
displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGAD
ped
). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%,
p
= 0.016).
Conclusion
First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.
This evidence- and consensus-based practical guideline for the diagnosis and treatment of Guillain-Barré Syndrome (GBS) in childhood and adolescence has been developed by a group of delegates from ...relevant specialist societies and organisations; it is the result of an initiative by the German-Speaking Society of Neuropediatrics (GNP), and is supported by the Association of Scientific Medical Societies (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften). A systematic analysis of the literature revealed that only a few adequately-controlled studies exist for this particular age group, while none carries a low risk of bias. For this reason, the diagnostic and therapeutic recommendations largely rely on findings in adult patients with GBS, for which there are a higher number of suitable studies available. Consensus was established using a written, multi-step Delphi process. A high level of consensus could be reached for the crucial steps in diagnosis and treatment. We recommend basing the diagnostic approach on the clinical criteria of GBS and deriving support from CSF and electrophysiological findings. Repetition of invasive procedures that yield ambiguous results is only recommended if the diagnosis cannot be ascertained from the other criteria. For severe or persistently-progressive GBS treatment with intravenous immunoglobulin (IVIG) is recommended, whereas in cases of IVIG intolerance or inefficacy we recommended treatment with plasmapheresis. Corticosteroids are ineffective for GBS but can be considered when acute onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is suspected due to a prolonged disease course. The full German version of the Guideline is available on the AWMF website (https://www.awmf.org/leitlinien/detail/ll/022-008.html).
•Diagnosis of GBS should be based on clinical course, distribution of weakness, typical electrophysiology and CSF-findings.•Painful diagnostic procedures should only be repeated if this is necessary for a clear diagnosis and treatment indication.•High-dose IVIG or plasma-exchange is the treatment modality of first choice proven with a satisfactory Level of Evidence.•Apparent non-responders have to be treated on individual decisions depending on details of the clinical course.•Combined rehabilitation procedures are necessary for all patients with significant disability.
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