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Deficiency of adenosine deaminase 2 (DADA2) is a rare Mendelian, autoinflammatory multiorgan disease. We report the case of a 3.8-year-old female patient who was admitted with an acute brainstem stroke and was diagnosed with DADA2 by early initiation of exome sequencing. We recommend that DADA2 and a genetic workup should be taken into account, when evaluating strokes in children even if no other than neurological symptoms are evident.

ZUSAMMENFASSUNGDie zahlreichen Einrichtungen für gesunde und kranke Kinder in Deutschland benötigen eine große Anzahl speziell pädiatrisch ausgebildeter Pflegekräfte. Der traditionelle Beruf der Gesundheits- und Kinderkrankenschwester hat sich seit mehr als hundert Jahren in Deutschland zu einem Beruf mit hoher Expertise entwickelt.Im Jahre 2020 wurde die generalistische Pflegeausbildung aus Gründen der Vergleichbarkeit und somit der länderübergreifenden Anerkennung der Berufsqualifikation in Europa eingeführt. Diese vereint nun die Gesundheits- und Krankenpflege, die Gesundheits- und Kinderkrankenpflege und die Altenpflege zu einer gemeinsamen Ausbildung mit dem Abschluss zur/m Pflegefachfrau/-mann. Dadurch wurden die Ausbildungszeiten in Theorie und Praxis für die pädiatrische Ausbildung stark reduziert. Die künftigen Abschlüsse der/s Pflegefachfrau/-manns erlauben den Einsatz zur Pflege von Kindern aller Altersstufen nach nur 60–120 Stunden praktischer Ausbildungszeit in der Pädiatrie – verglichen mit annähernd 2500 Stunden nach dem vorherigen Ausbildungskonzept.In dem Artikel wird erläutert, warum aus Sicht der Pädiatrie zwei Lösungsansätze sinnvoll sind: einerseits das Angebot der pädiatrischen Vertiefung im Rahmen der generalistischen Pflegeausbildung an allen Kliniken für Kinder und Jugendliche oder großen Kinderfachabteilungen; andererseits eine einjährige Spezialisierung zum/r Gesundheits- und Kinderkrankenpfleger/in nach der generalistischen Pflegeausbildung entsprechend dem europäischen Vorbild.

The Kennedy pathways catalyse the de novo synthesis of phosphatidylcholine and phosphatidylethanolamine, the most abundant components of eukaryotic cell membranes. In recent years, these pathways have moved into clinical focus because four of ten genes involved have been associated with a range of autosomal recessive rare diseases such as a neurodevelopmental disorder with muscular dystrophy (CHKB), bone abnormalities and cone-rod dystrophy (PCYT1A) and spastic paraplegia (PCYT2, SELENOI). We identified six individuals from five families with bi-allelic variants in CHKA presenting with severe global developmental delay, epilepsy, movement disorders and microcephaly. Using structural molecular modelling and functional testing of the variants in a cell-based Saccharomyces cerevisiae model, we determined that these variants reduce the enzymatic activity of CHKA and confer a significant impairment of the first enzymatic step of the Kennedy pathway. In summary, we present CHKA as a novel autosomal recessive gene for a neurodevelopmental disorder with epilepsy and microcephaly.

Objectives Depositions of linear gadolinium-based MRI contrast agents are readily visible in T1-weighted MRIs of certain brain regions in both adults and children. Macrocyclic contrast agents such as gadobutrol have so far escaped detection by qualitative MRI in children. This study aimed to assess whether there is evidence for deposition of gadobutrol in children using quantitative T1 mapping. Methods This retrospective study included patients, naive to other gadolinium-based contrast agents than gadobutrol, who had received gadobutrol as part of a clinically indicated MRI. For each patient, T1 relaxation times at 3 T were measured using single-shot T1 mapping at two time points. In each of six brain regions, age-adjusted T1 relaxation times were correlated with a number of previous gadobutrol administrations. To combine interindividual, cross-sectional effects with intraindividual, longitudinal effects, both linear mixed model and generalized additive mixed model were applied. Results One hundred four examinations of 52 children (age median 11.4, IQR 6.3–15, 26 female) with a median of 7 doses of gadobutrol in the history of their neurological or neurooncological disease were included. After correction for age and indeterminate disease-related effects to T1 time, a negative correlation of T1 time with the number of gadobutrol doses administered was observed in both mixed models in the putamen (beta − 1.65, p = .03) and globus pallidus (beta − 1.98, p = .012) Conclusions The results indicate that in children, gadobutrol is deposited in the globus pallidus and putamen. Key Points • Previous gadobutrol administration correlates with reduced T1 relaxation times in the globus pallidus and putamen in children. • This decreased T1 might be caused by gadobutrol retention within these gray-matter nuclei.

ZUSAMMENFASSUNGHoloprosenzephalie (HPE) ist ein komplexes Krankheitsbild mit variabler genetischer und klinischer Ausprägung. Es existieren verschiedene Formen der HPE mit Unterschieden in der Schwere des Verlaufes. Die schwere Form der HPE stellen die lobare und alobare HPE dar, die mit Zyklopie (Vereinigung von beiden Augenanlagen in einer einzigen Orbita) einhergehen, wohingegen Minor-Formen/HPE-Spektrumerkrankungen eine Mikrozephalie und/oder Hypotelorismus oder eine Lippen-Kiefer-Gaumenspalte aufweisen. Die genetischen Mechanismen sind noch nicht abschließend geklärt. Es wurden autosomal-dominante, rezessive und digenetische Vererbungsmuster beschrieben. Wir ergänzen das Spektrum der HPE-Erkrankungen um eine Patientin mit compound heterozygoter DISP1-Mutation, die einen Panhypopituitarismus in Kombination mit Entwicklungverzögerung, Lippen-Kiefer-Gaumenspalte, persistierendem Ductus Arteriosus Botalli und Visusminderung aufweist.

Background: Obesity in childhood and adolescence remains a great global health challenge. Stress exposure during childhood and adolescence is associated with a higher risk for obesity, yet the linkage between stress and obesity is multidimensional, and its biological and behavioral mechanisms are still not fully understood. Summary: In this literature review, we identified different types of stress exposure in children and adolescents, including first studied effects of the COVID-19 pandemic as a prolonged stress exposure and their association with obesity risk. We investigated studies on the connection of altered stress biology and behavioral pathways as well as intervention programs on stress reduction in children and adolescents with obesity. Key Messages: There is evidence that stress exposure in childhood and adolescence promotes biological and behavioral alterations that contribute to the multifactorial pathogenesis of obesity. COVID-19 related-stress presents the most current example of a negative influence on weight development in children and adolescents. However, longitudinal studies on the linkage between environmental, behavioral, and biological factors across development are few, and results are partly equivocal. Intervention programs to reduce stress in children through mindfulness might be a promising adjunctive tool in the prevention and treatment of childhood and adolescent obesity that could further offer proof of concept of theoretically elaborated cause-and-effect relationships.

Objective: This study focuses on treatment of multiloculated hydrocephalus (HCP) following ventricular infection. Post-infectious hydrocephalus in the premature infant is a complicated disease and dire to treat as it tends to re-occur despite multiple surgical procedures. Here, we report our experience in rtPA (recombinant tissue-type plasminogen activator) application and neuroendoscopic lavage to treat post-infectious HCP. Methods: This retrospective series comprises on six premature infants with a history of intraventricular infection. In the course of treatment, neuroendoscopy, external ventricular drainage, antibiotic treatment and lavage have been performed. rtPA has been applied intraventricularily in three patients in individual regimen (s. below) to dissolve membranes, septs and cysts to facilitate cerebro-spinal fluid (CSF) circulation. Besides clinical outcome CSF and laboratory parameters as well as MR/sonographic morphology are evaluated.Results: Here, rtPA application did not cause hemorrhagic complications. Improvement of CSF parameters, such as lactate, glucose and protein levels, was limited while MRI and ultrasound imaging demonstrated successful dissolving of intraventricular septs and cysts. The overall neurological outcome was poor. Thus, a beneficial impact of rtPA installation on the neurological outcome remains uncertain.Conclusion: In our experience, rtPA was safely instilled to dissolve intraventricular septation and to reduce protein precipitation in ventriculitis in neonates and preterm infants. Shunt interventions were presumably reduced in our cohort, probably due to prevention of multiloculated hydrocephalus. A beneficial impact on neurological status was absent as clinical outcome was generally poor. Outcome scores did not apply, or showed no difference, respectively.

Introduction Although intrathecal baclofen (ITB) therapy is an effective treatment for spasticity, it has several disadvantages and a risk of complications. Methods We present six pediatric patients who suffered from unusual mechanical failures of intrathecal baclofen pump systems. Results With these case-vignettes, we provide a systematic approach on how to interpret the symptoms of ITB complications and an advice which further diagnostic and therapeutic steps to follow. We underline the seriousness of baclofen overdose, underdosing or withdrawal.

Background Quantitative mapping of MRI relaxation times is expected to uncover pathological processes in the brain more subtly than standard MRI techniques with weighted contrasts. So far, however, most mapping techniques suffer from a long measuring time, low spatial resolution or even sensitivity to magnetic field inhomogeneity. Objective To obtain T1 relaxation times of the normal brain from early infancy to adulthood using a novel technique for fast and accurate T1 mapping at high spatial resolution. Materials and methods We performed whole-brain T1 mapping within less than 3 min in 100 patients between 2 months and 18 years of age with normal brain at a field strength of 3 T. We analyzed T1 relaxation times in several gray-matter nuclei and white matter. Subsequently, we derived regression equations for mean value and confidence interval. Results T1 relaxation times of the pediatric brain rapidly decrease in all regions within the first 3 years of age, followed by a significantly weaker decrease until adulthood. These characteristics are more pronounced in white matter than in deep gray matter. Conclusion Regardless of age, quantitative T1 mapping of the pediatric brain is feasible in clinical practice. Normal age-dependent values should contribute to improved discrimination of subtle intracerebral alterations.

Even though shunt surgery has been an established and widely accepted treatment for congenital hydrocephalus for five decades, long-term follow-up and functional outcome data are scarce. Based on our experience, we advocate a very rigid follow-up regimen throughout life for every hydrocephalus patient encountered with individual screening intervals not longer than 1 year in childhood and adolescence and surveillance intervals of 2 years in adulthood. A continuous treatment of the patients at the primary institution that performed hydrocephalus surgery provides an optimal setting to be prepared for the detection of adverse events of shunt malfunctioning. However, some patients may still encounter catastrophic events resulting in persistent deficits or death.

Moyamoya disease (MMD) is characterized by bilateral, chronic progressive stenosis at the terminal portions of the internal carotid arteries and their proximal branches. The “smoke-like” appearance of the arterial collaterals in angiography gives the disease its name. The “ivy-sign” is the less-known magnetic resonance imaging (MRI) pattern of this disease. The leptomeningeal collaterals present as diffuse signal enhancement at the brain surface in contrast-enhanced T1-weighted image and fluid-attenuated inversion recovery sequences “as if overgrown with ivy.”We report on three patients with MMD in whom the “ivy-sign” was already present but misinterpreted in the initial MRI of the brain. The correct diagnosis was made only after repeated MRI.Using three case studies, we describe the difficulties in the interpretation of the “ivy-sign” as an MRI pattern. Knowledge of the “ivy-sign” can be helpful, especially in diseases predisposing to MMD. If this MRI pattern is present, MMD should be considered and MR angiography should be added.

Objective The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. Case Study We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. Conclusion We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

Background and ObjectiveThe spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody–associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG‐IgG titers in children with MOGAD in correlation with clinical presentation and disease course.MethodsIn this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG–positive.ResultsOne hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG–negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG–negative.DiscussionIn this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG–negative, are shown to have a significantly reduced relapse risk.

Calcium (Ca2+) is a universal second messenger involved in synaptogenesis and cell survival; consequently, its regulation is important for neurons. ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) belongs to the family of ATP-driven calmodulin-dependent Ca2+ pumps that participate in the regulation of intracellular free Ca2+. Here, we clinically describe a cohort of 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism, seizures, and distal limb abnormalities. Nine probands harbor missense variants, seven of which were in specific functional domains, and three individuals have nonsense variants. 3D structural protein modeling suggested that the variants have a destabilizing effect on the protein. We performed Ca2+ imaging after introducing all nine missense variants in transfected HEK293 cells and showed that all variants lead to a significant decrease in Ca2+ export capacity compared with the wild-type construct, thus proving their pathogenicity. Furthermore, we observed for the same variant set an incorrect intracellular localization of ATP2B1. The genetic findings and the overlapping phenotype of the probands as well as the functional analyses imply that de novo variants in ATP2B1 lead to a monogenic form of neurodevelopmental disorder.

ZUSAMMENFASSUNGBasierend auf dem bio-psycho-sozialen Modell von Krankheit und Gesundheit beschäftigt sich die Neuropädiatrie mit dissoziativen und somatoformen Störungen des Kindes- und Jugendalters. Besonders die sog. Konversionsstörungen führen zu einer häufigen Inanspruchnahme des Kinderneurologen. Die nicht willentlich erzeugte Symptomatik basiert nicht auf einer identifizierbaren organischen Ursache und ist inkompatibel mit anatomischen und physiologischen Gesetzmäßigkeiten oder bekannten neurologischen Erkrankungen. Sie bedeuten für den Patienten und seine Familie eine erhebliche psychoemotionale Belastung und Funktionseinschränkung. Die Störungsbilder bergen das Risiko unnötiger und belastender Diagnostik und – mitunter invasiver – Therapie. Die Prognose psychotherapeutischer Interventionen ist umso günstiger je kürzer das Zeitintervall zwischen Manifestation und Diagnosestellung ist.

ZUSAMMENFASSUNGMigräne und Spannungskopfschmerzen sind die häufigsten idiopathischen Kopfschmerzsyndrome im Kindes- und Jugendalter. Aufgrund ihrer hohen Prävalenz und dem oft hohen Leidensdruck bei den Betroffenen sind sie ein häufiger Grund für Vorstellungen im ambulanten oder stationären Setting. Dieser Artikel fasst die aktuelle Literatur und die Empfehlungen zur Akuttherapie und prophylaktischen Behandlung von Migräne und Spannungskopfschmerzen zusammen.

ZUSAMMENFASSUNGEin Status epilepticus stellt einen Notfall dar, der mit einer erheblichen Morbidität und Mortalität einhergeht. Aus operationaler Sicht wird daher mittlerweile ein Status epilepticus in der Erwachsenenneurologie ab einer Anfallsdauer von 5 Minuten definiert. Der Notfalltherapie sowohl im Laien- als auch im Klinikbereich kommt eine sehr wichtige Rolle zu. Therapie der ersten Wahl sind weiterhin Benzodiazepine. Zunehmend positive Erfahrungen und Studienergebnisse liegen für Valproat, Levetiracetam und Lacosamid auch für pädiatrische Patienten vor.

ZUSAMMENFASSUNGNusinersen (Spinraza® ) ist das einzige bislang zugelassene Medikament zur Therapie der spinalen Muskelatrophien (SMA). In der EU besteht die Zulassung als Orphan Drug seit Anfang 2016 und gilt für alle Formen der spinalen Muskelatrophien. Dieser Artikel gibt einen Überblick über Wirkmechanismus und Anwendung des Medikaments sowie erste klinische Erfahrungswerte nach 3 Jahren der Behandlung von Patienten mit SMA an der Universitätsklinik für Kinder- und Jugendmedizin Leipzig.

ZUSAMMENFASSUNGVorgestellt werden die aktuellen Behandlungsoptionen bei infantilen Spasmen (früher BNS-Epilepsie) in Form eines Stufenschemas. Berücksichtigung finden die deutsche AWMF-Leitlinie 14 sowie die Behandlungsdaten und aktuellen 18-Monats-Nachbeobachtungsergebnisse der internationalen Behandlungsstudie „ICISS“ mit Vergleich einer primären Kombinationstherapie aus Vigabatrin und Prednisolon versus Vigabatrin und ACTH 10, 11.Dargestellt werden typische und weniger bekannte Symptome bei infantilen Spasmen zur Früherkennung, die Nomenklatur im Bereich West-Syndrom/BNS-Epilepsie, außerdem die Möglichkeiten der akuten Diagnostik und Hinweise auf das Nebenwirkungsspektrum der Therapien.

The Kennedy pathways catalyze the de novo synthesis of phosphatidylcholine and phosphatidylethanolamine, the most abundant components of eukaryotic cell membranes. In recent years, these pathways have moved into clinical focus since four out of ten genes involved have been associated with a range of autosomal recessive rare diseases such as a neurodevelopmental disorder with muscular dystrophy (CHKB), bone abnormalities and cone-rod dystrophy (PCYT1A), and spastic paraplegia (PCYT2, SELENOI).We identified six individuals from five families with bi-allelic variants in CHKA presenting with severe global developmental delay, epilepsy, movement disorders, and microcephaly. Using structural molecular modeling and functional testing of the variants in a in a cell-based S. cerevisiae model, we determined that these variants reduce the enzymatic activity of CHKA and confer a significant impairment of the first enzymatic step of the Kennedy pathway.In summary, we present CHKA as a novel autosomal recessive gene for a neurodevelopmental disorder with epilepsy and microcephaly.

TUBA1A tubulinopathy is a rare neurodevelopmental disorder associated with brain malformations as well as early-onset and intractable epilepsy. As pathomechanisms and genotype-phenotype correlations are not completely understood, we aimed to provide further insights into the phenotypic and genetic spectrum. We here present a multicenter case series of ten unrelated individuals from four European countries using systematic MRI re-evaluation, protein structure analysis, and prediction score modeling. In two cases, pregnancy was terminated due to brain malformations. Amongst the eight living individuals, the phenotypic range showed various severity. Global developmental delay and severe motor impairment with tetraparesis was present in 63% and 50% of the subjects, respectively. Epilepsy was observed in 75% of the cases, which showed infantile onset in 83% and a refractory course in 50%. One individual presented a novel TUBA1A-associated electroclinical phenotype with evolvement from early myoclonic encephalopathy to continuous spike-and-wave during sleep. Neuroradiological features comprised a heterogeneous spectrum of cortical and extracortical malformations including rare findings such as cobblestone lissencephaly and subcortical band heterotopia. Two individuals developed hydrocephalus with subsequent posterior infarction. We report four novel and five previously published TUBA1A missense variants whose resulting amino acid substitutions likely affect longitudinal, lateral, and motor protein interactions as well as GTP binding. Assessment of pathogenic and benign variant distributions in synopsis with prediction scores revealed sections of variant enrichment and intolerance to missense variation. We here extend the clinical, neuroradiological, and genetic spectrum of TUBA1A tubulinopathy and provide insights into residue-specific pathomechanisms and genotype-phenotype correlations.

ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential nature of this process for cellular function, there is little information on the role of RISC components in human development and organ function. We identify 13 heterozygous mutations in AGO2 in 21 patients affected by disturbances in neurological development. Each of the identified single amino acid mutations result in impaired shRNA-mediated silencing. We observe either impaired RISC formation or increased binding of AGO2 to mRNA targets as mutation specific functional consequences. The latter is supported by decreased phosphorylation of a C-terminal serine cluster involved in mRNA target release, increased formation of dendritic P-bodies in neurons and global transcriptome alterations in patient-derived primary fibroblasts. Our data emphasize the importance of gene expression regulation through the dynamic AGO2-RNA association for human neuronal development., AGO2 binds to miRNAs to repress expression of cognate target mRNAs. Here the authors report that heterozygous AGO2 mutations result in defects in neurological development and impair RNA interference.

Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G&gt, T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum.

Background A rare symptom of Glut1 deficiency syndrome (Glut1 DS) is hemiplegic migraine (HM). Case We report a patient with Glut1 DS with a mild phenotype. His leading symptom was HM. As an unusual complication of the initiation of a ketogenic diet (KD), our patient developed paroxysmal nonkinesigenic dyskinesia. Paroxysmal dyskinesia occurred first and exclusively at the initiation of KD. Literature review There are a few case reports for HM in Glut1 DS. All patients had additional neurological symptoms. Regarding central nervous system symptoms such as paroxysmal dyskinesia triggered by KD, we found only 1 other case report. Discussion HM is part of the symptom complex of Glut1 DS and can be effectively treated by KD. Paroxysmal dyskinesia trigged by the initiation of KD should not lead to the discontinuation of the diet in Glut1 DS.

Bilateral optic neuritis (bilON) is a rare clinical presentation often thought to be associated with relapsing disorders such as neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS).To characterize the clinical, radiological phenotype and antibody status of children presenting with bilON.Retrospective multicenter study on children with bilON age18 years with a first episode aquired demyelinating syndrome (ADS), cMRI, AQP4- and serum MOG-antibody status and follow-up data were collected.30 patients (f:m = 15:15, median age 8.0y) with bilON met the inclusion criteria. 22/30 (73%) were MOG-positive (median: 1:1280, range: 1:160-1:1520). No patient showed AQP4-abs. 4/30 patients (13%), all with high MOG-abs titers, had recurrent episodes. No patient developed MS. Improvement after IVMP was observed in most patients (26/30; 87%). Outcome was favorable with no sequelae in 22/30 patients. Serial MOG-abs titers tested in 15/22 patients decreased to a median of 1:160 (range: 0-1:640) over a period of 31 months (range: 2-141 months) in 14/15 (93%) patients. MR imaging showed a predominantly anterior affection of the visual system in seropositive patients with bilateral intraorbital lesions in 68% (15/22), compared to 25% in MOG-negative patients (2/8).Pediatric bilON is associated with high MOG-abs titers in combination with anterior involvement of the visual system. Despite severe loss of vision, the majority of patients shows distinct recovery after IVMP.

Polytrauma in children is rare but potentially life-threatening. At the site of the accident the physician has to stabilize respiration and circulation to achieve normoxia and normotonia. The Glasgow Coma Scale allows for assessment of the severity of the trauma and for an estimate of the prognosis. Accompanying lesions such as internal bleeding, spine fractures or peripheral nerve lesions have to be assessed. The patient will be transferred to a pediatric intensive care unit in a hospital with neurosurgical facilities. After eventual (neuro)surgical interventions, cerebral perfusion pressure has to be monitored and maintained. Early start of physiotherapy and supportive care involving parents and families enables a successful rehabilitation.

Background New-generation, cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD). Objective To describe systematically the CSF profile in children with MOG-EM. Material and methods Cytological and biochemical findings (including white cell counts [WCC] and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgM/IgA fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster [MRZ] reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF l-lactate) from 108 lumbar punctures in 80 pediatric patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively. Results Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in 89% of samples (N = 96), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 29). If present at all, intrathecal IgG synthesis was low, often transient and mostly restricted to acute attacks. Intrathecal IgM synthesis was present in 21% and exclusively detectable during acute attacks. CSF WCC were elevated in 54% of samples (median 40 cells/μl; range 6–256; mostly lymphocytes and monocytes; > 100/μl in 11%). Neutrophils were present in 71% of samples; eosinophils, activated lymphocytes, and plasma cells were seen only rarely (all N = 79) and at least once in 48% of all patients (N = 67) tested. CSF alterations were significantly more frequent and/or more pronounced in patients with acute spinal cord or brain disease than in patients with acute ON and varied strongly depending on attack severity. CSF l-lactate levels correlated significantly with the spinal cord lesions load (measured in vertebral segments) in patients with acute myelitis (p = 0.0099). An analysis of pooled data from the pediatric and the adult cohort showed a significant relationship of QAlb (p < 0.0005), CST TP (p < 0.0001), and CSF l-lactate (p < 0.0003) during acute attacks with age. Conclusion MOG-IgG-associated EM in children is characterized by CSF features that are distinct from those in MS. With regard to most parameters, no marked differences between the pediatric cohort and the adult cohort analyzed in Part 1 were noted. Our findings are important for the differential diagnosis of pediatric MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.

Background Accumulating evidence suggests a relationship between sleep alterations and overweight/obesity in children. Our aim was to investigate the association of sleep measures other than obstructive sleep apnea or sleep duration with overweight/obesity and metabolic function in children. Methods We conducted a prospective cohort study in school- aged children (aged 5 to 8 years, prepubertal, and 12 to 15 years, pubertal) with overweight/obesity and normal-weight children. All children underwent a standardized in-laboratory polysomnography followed by a fasting blood assessment for glucose and metabolic testing. Subjective sleep measures were investigated by a 7-day sleep diary and questionnaire. We analyzed prepubertal and pubertal groups separately using logistic regression and partial correlation analyses. Results A total of 151 participants were analyzed. Overweight/obese children had significantly higher odds for arousal index (prepubertal children: 1.28, Confidence interval (CI): 1.06, 1.67; pubertal children: 1.65, CI: 1.19, 2.29) than normal-weight children, independent of age and gender. In prepubertal children, arousal-index was positively associated with C-peptide (r=0.30, p=0.01), whereas Minimum O2 saturation was negatively associated with triglycerides (r=−0.34, p=0.005), adjusting for age and sex. However, associations were attenuated by further adjustment for body mass index standard deviation scores (BMI-SDS). In pubertal children, higher level of apnea-hypopnea-index and pCO2 predicted increased lipoprotein (a) levels (r=0.35, p=0.03 and r=0.40, p=0.01, respectively), independent of age, sex, and BMI-SDS. A negative association was found between pCO2 and high-density lipoprotein (HDL)-cholesterol (r=−0.40, p=0.01). Conclusions Overall, we report that sleep quality as measured by arousal index may be compromised by overweight and obesity in children and warrants attention in future intervention programs.

Objective Parents of children with epilepsy are at risk of committing high-risk handling errors with a high potential to harm the patient when administering anticonvulsant rescue medication. We developed a training concept addressing identified high-risk handling errors and investigated its effects on parents' skills. Study design In a controlled prospective intervention study, parents of children with epilepsy were asked to demonstrate their administration of rescue medication by using dummy dolls. A clinical pharmacist monitored rectal or buccal administration and addressed errors in the intervention group with training and information sheets. Three to 6 weeks later, intervention's sustainability was assessed at a home visit. Results One hundred sixty-one parents completed full study assessment: 92 in the intervention group and 69 in the control group. The number of processes with at least one handling error was reduced from 96.4% to 56.7% in rectal tube administration and from 66.7% to 13.5% in buccal administration (both p Conclusion A one-time intervention for parents significantly and sustainably reduced high-risk handling errors. Dummy dolls and information sheet were adequate for an effective and feasible training to support the correct administration of anticonvulsant rescue medication.

A developmental disorder of a child has a major impact on the affected families' lives. However, data about the parents' perception of the revealing of the diagnosis is scarce.Parents of children with developmental disorder treated as outpatients in a university hospital were interviewed about the initial medical consultation concerning the diagnosis of their child.Parents of 210 children agreed to take part in the study. 35/210 (17%) had to be excluded from the study as they were not able to remember the initial medical consultation, or claimed there was either no initial medical consultation or they did not attend it. The diagnosis of developmental disorder was made in median 4 months (Q25/Q75: 0/12; min/max: 0/63) after the parents had noticed the first symptoms. According to the parents, options to support the development of the child were the most frequently addressed topic in the initial medical consultation (119/175, 68%). Some parents wished more empathy (19/175, 11%), and less medical terminology (12/175, 7%). 114/175 (65%) of parents rated the initial medical consultation as "very good" or "good". After their initial medical consultation, 66/175 (38%) of the parents had open questions mainly concerning the prognosis of the disease. Sources of information that were used after the consultation were most often the treating physician (150/175, 86%) and the internet (133/175, 76%).Generally, parents perceive the initial medical consultation on the developmental disorder of their child well. Nevertheless, many parents state that they had unanswered questions after the consultation. The internet is one of the main sources parents use to answer those questions.Die Entwicklungsverzögerung eines Kindes hat einen erheblichen Einfluss auf das Leben betroffener Familien. Es gibt jedoch kaum Daten darüber, wie Eltern die Diagnoseeröffnung erleben.Eltern, deren Kinder ambulant in einer Universitätsklinik behandelt wurden, wurden zum ärztlichen Erstgespräch zur Diagnose ihres Kindes befragt.Eltern von 210 Kindern stimmten der Teilnahme zu. 35/210 (17%) mussten ausgeschlossen werden, weil sie sich entweder nicht an das Erstgespräch erinnern konnten oder angaben, dass ein solches Gespräch nie stattgefunden habe oder sie nicht daran teilgenommen haben. Die Diagnose Entwicklungsverzögerung wurde im Median 4 Monate (Q25/Q75: 0/12; min/max: 0/63), nachdem die Eltern die ersten Symptome beobachtet hatten, gestellt. Laut Eltern wurden im Erstgespräch insbesondere Unterstützungsmöglichkeiten für die Entwicklung des Kindes besprochen (119/175, 68%). Einige Eltern wünschten sich mehr Empathie (19/175, 11%) und weniger medizinische Fachausdrücke (12/175, 7%). 114/175 (65%) der Eltern bewerteten das Gespräch als „sehr gut“ oder „gut“. Nach dem Erstgespräch hatten 66/175 (38%) der Eltern offene Fragen, insbesondere bezüglich der Prognose der Erkrankung. Als Hauptinformationsquellen nach dem Erstgespräch dienten der behandelnde Arzt (150/175, 86%) und das Internet (133/175, 76%).Im Allgemeinen empfinden Eltern das Erstgespräch zur Entwicklungsverzögerung ihres Kindes positiv. Dennoch geben viele Eltern an, dass sie nach dem Erstgespräch offene Fragen hatten. Das Internet ist eine der Hauptinformationsquellen, die Eltern zur Beantwortung dieser Fragen nutzen.