De novo variants in RNF213 are associated with a clinical spectrum ranging from Leigh syndrome to early-onset stroke.

PURPOSE: RNF213, encoding a giant E3 ubiquitin ligase, has been recognized for its role as a key susceptibility gene for moyamoya disease. Case reports have also implicated specific variants in RNF213 with an early-onset form of moyamoya disease with full penetrance. We aimed to expand the phenotypic spectrum of monogenic RNF213-related disease and to evaluate genotype-phenotype correlations. METHODS: Patients were identified through reanalysis of exome sequencing data of an unselected cohort of unsolved pediatric cases and through GeneMatcher or ClinVar. Functional characterization was done by proteomics analysis and oxidative phosphorylation enzyme activities using patient-derived fibroblasts. RESULTS: We identified 14 individuals from 13 unrelated families with (de novo) missense variants in RNF213 clustering within or around the Really Interesting New Gene (RING) domain. Individuals presented either with early-onset stroke (n = 11) or with Leigh syndrome (n = 3). No genotype-phenotype correlation could be established. Proteomics using patient-derived fibroblasts revealed no significant differences between clinical subgroups. 3D modeling revealed a clustering of missense variants in the tertiary structure of RNF213 potentially affecting zinc-binding suggesting a gain-of-function or dominant negative effect. CONCLUSION: De novo missense variants in RNF213 clustering in the E3 RING or other regions affecting zinc-binding lead to an early-onset syndrome characterized by stroke or Leigh syndrome.

[Arterial ischemic stroke in childhood and adolescence : Time-critical emergency in pediatrics]. / Arteriell ischämischer Schlaganfall im Kindes- und Jugendalter : Zeitkritischer Notfall in der Pädiatrie.

Childhood arterial ischemic stroke is one of the most time-critical pediatric emergencies but is often diagnosed with a prognostically relevant time delay. The reasons are low awareness, sometimes unspecific clinical presentation with a wide variety of critical differential diagnoses and less coordinated acute care structures. The revascularization strategies established for adults also show sometimes spectacular success in children. These should therefore also be made available for affected children if possible, although the evidence is nowhere near comparable. In the postacute phase the etiological work-up is complex due to the risk factors which need to be considered, but identification of the individual risk profile is essential as it defines secondary prevention, risk of recurrence and outcome. The long-term care in a multiprofessional, interdisciplinary team must take into account all bio-psycho-social aspects of the child in the current developmental phase.

[Stroke alarm-Arterial ischemic stroke as one of the most time-critical emergencies in children and adolescents]. / Notfall-Neuropädiatrie ­ Der arteriell ischämische Schlaganfall als einer der zeitkritischsten Notfälle bei Kindern und Jugendlichen.

Arterial ischemic stroke in childhood and adolescence is one of the most time-critical emergencies in pediatrics. Nevertheless, it is often diagnosed with a considerable time delay which may be associated with low awareness, the sometimes nonspecific clinical presentation with a wide variety of differential diagnoses, and less established 'acute care structures'. The revascularisation strategies in adult stroke care are also potential and promising treatment options for children, even if available evidence is still limited. In the post-acute phase, the etiological work-up is complex due to the multitude of risk factors to be considered. But it is essential to identify each child's individual risk profile as it determines secondary prevention, risk of recurrence and outcome. Long-term care in a multiprofessional, interdisciplinary team must take into account the bio-psycho-social aspects to integrate the child into its social and educational, and later professional environment.

Migraine and the development of additional psychiatric and pain disorders in the transition from adolescence to adulthood.

INTRODUCTION: The transition from childhood to adolescence and from adolescence to adulthood are vulnerable phases in life. In these phases, late or insufficient treatment of diseases may lead to chronification and favor development of additional disorders. In adolescents, migraine often has a highly negative impact on school performance and everyday life. The hypothesis of the present study was that adolescents with migraine have a higher risk for developing additional disorders such as psychiatric disorders or other pain syndromes in the course of the disease. MATERIALS AND METHODS: In this study, we analyzed health insurance data of 56,597 German adolescents at the age of 15 years in the year 2006. By using the International Classification of Diseases (ICD 10), we determined a group with migraine diagnosis in the year 2006 and a control group without any headache diagnosis in 2006. We then compared both groups regarding the development of additional disorders (based on the ICD 10) during the following 10 years (2007 to 2016). RESULTS: Adolescents with migraine had a 2.1 fold higher risk than persons without migraine diagnosis to develop an additional affective or mood disorder, a 1.8 fold higher risk to obtain neurotic, stress-related and somatoform disorders, a 1.8 fold higher risk to subsequently suffer from behavioral syndromes, a 1.6 higher risk to get back pain and a 1.5 fold higher risk for irritable bowel syndrome during the next 10 years. CONCLUSION: Adolescents with migraine are at risk for developing additional disorders later. Considering and addressing the patient's risks and potential medical and psychosocial problems might improve the long-term outcome significantly.

Incidence and risk factors of cerebral sinovenous thrombosis in infants.

AIM: To describe the incidence of term and preterm neonatal cerebral sinovenous thrombosis (CSVT) and identify perinatal risk factors. METHOD: This was a national capture-recapture calculation-corrected surveillance and nested case-control study. Infants born preterm and at term with magnetic resonance imaging-confirmed neonatal CSVT were identified by surveillance in all paediatric hospitals in Germany (2015-2017). Incidence was corrected for underreporting using a capture-recapture method in one federal state and then extrapolated nationwide. We reviewed PubMed for comparisons with previously reported incidence estimators. We used a population-based perinatal database for quality assurance to select four controls per case and applied univariate and multivariable regression for risk factor analysis. RESULTS: Fifty-one newborn infants (34 males, 17 females; 14 born preterm) with neonatal CSVT were reported in the 3-year period. The incidence of term and preterm neonatal CSVT was 6.6 (95% confidence interval [CI] 4.4-8.7) per 100 000 live births. Median age at time of confirmation of the diagnosis was 9.95 days (range 0-39d). In the univariate analysis, male sex, preterm birth, hypoxia and related indicators (umbilical artery pH <7.1; 5-minute Apgar score <7; intubation/mask ventilation; perinatal asphyxia), operative vaginal delivery, emergency Caesarean section, and pathological fetal Doppler sonography were associated (p<0.05) with neonatal CSVT. Multivariable regression yielded hypoxia (odds ratio=20.3; 95% CI 8.1-50.8) as the independent risk factor. INTERPRETATION: Incidence of neonatal CSVT was within the range of other population-based studies. The results suggest that hypoxia is an important perinatal risk factor for the aetiology of neonatal CSVT.

Comparison of a pediatric practice-based therapy and an interdisciplinary ambulatory treatment in social pediatric centers for migraine in children: a nation-wide randomized-controlled trial in Germany: "moma - modules on migraine activity".

BACKGROUND: Migraine is common in childhood, peaks in adolescents and persists into adulthood in at least 40% of patients. There is need for early interventions to improve the burden of disease and, if possible, reduce chronification. The aim of the project is to compare two types of ambulatory treatment strategies regarding their effect on headache days and quality of life in 6 to 11 year old children with migraine: 1) the routine care in pediatricians' practices (intervention group A) and 2) a structured interdisciplinary multimodal intervention administered at social pediatric centers (intervention group B). METHODS: The study is a nation-wide cluster-randomized study. Based on the postal codes the regions are randomly assigned to the two intervention-strategies. Children with migraine are recruited in the pediatric practices, as common outpatient-care in the German health-care system. Parents rate headache frequency, intensity and acute medication intake at a daily basis via a digital smartphone application specifically designed for the study. Migraine-related disability and quality of life are assessed every 3 months. Study duration is 9 months for every participant: 3 months of baseline at the pediatric practice (both groups); 3 months of intervention at the pediatric practice (intervention group A) or at the social pediatric center (intervention group B), respectively; 3 months of follow-up at the pediatric practice (both groups). DISCUSSION: Results of the planned comparison of routine care in pediatric practices and interdisciplinary social pediatric centers will be relevant for treatment of children with migraine, both for the individual and for the health care system. TRIAL REGISTRATION: The study was approved by the ethics committee at the Ludwig-Maximilians-University Munich (number 18-804) and was retrospectively registered on 27 April 2021 in the WHO approved German Clinical Trials Register (number DRKS00016698 ).

Motor outcome, executive functioning, and health-related quality of life of children, adolescents, and young adults after ventricular assist device and heart transplantation.

OBJECTIVE: The aim of the current study is to measure long-term executive function, motor outcome, and QoL in children, adolescents, and young adults after VAD and Htx. METHODS: Patients were examined during routine follow-up. Investigation tools were used as follows: Examination for MND of motor outcomes, Epitrack® for attention and executive functioning, and Kidscreen-52 and EQ-5D-5L questionnaires for QoL. Additional data were retrospectively obtained by an analysis of patient medical records. RESULTS: Out of 145 heart transplant recipients at the department of pediatric cardiology of the University Hospital Munich, 39 were implanted with a VAD between 1992 and 2016. Seventeen (43.6%) patients died before or after Htx; 22 (56.4%) patients were included in our study. Mean age at transplant was 9.52 years (range: 0.58-24.39 years, median 9), and the mean follow-up time after Htx was 6.18 years (range: 0.05-14.60 years, median 5.82). MND examination could be performed in 13 patients (normal MND: n = 11, simple MND: n = 1, complex MND: n = 1). Executive functioning was tested in 15 patients. Two (13.3%) patients had good results, six (40%) average results, three (20%) borderline results, and four (26.7%) impaired results. QoL (Kidscreen n = 7, EQ-5D-5L n = 8) was similar to a healthy German population. CONCLUSION: Motor outcome, executive functioning and QoL in survivors of VAD bridging therapy and Htx can be good, though underlying diseases and therapies are associated with a high risk of cerebral ischemic or hemorrhagic complications.

Risk factors for perinatal arterial ischaemic stroke: a large case-control study.

AIM: To identify maternal, obstetric, and neonatal risk factors related to perinatal arterial ischaemic stroke (PAIS) diagnosed within 28 days after birth and to understand the underlying pathophysiology. METHOD: For case and control ascertainment, we used active surveillance in 345 paediatric hospitals and a population-based perinatal database for quality assurance of hospital care. We analysed complete cases of PAIS using logistic regression. Multivariate analysis was guided by a directed acyclic graph. RESULTS: After exclusion of records with missing data, we analysed 134 individuals with PAIS and 576 comparison individuals. In univariate analysis, male sex, preterm birth (<37wks gestational age), small for gestational age (SGA), low umbilical artery pH (<7.1), low 5-minute-Apgar score (<7), multiple pregnancies, hypoxia, intubation/mask ventilation, nulliparity, Caesarean section, vaginal-operative delivery, chorioamnionitis, and oligohydramnios were associated with an increased risk. Mutual adjustment yielded male sex (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.20-2.73), multiple birth (OR 3.22; 95% CI 1.21-8.58), chorioamnionitis (OR 9.89; 95% CI 2.88-33.94), preterm birth (OR 1.86; 95% CI 1.01-3.43), and SGA (OR 3.05; 95% CI 1.76-5.28) as independent risk factors. INTERPRETATION: We confirmed the increased risk in males and the role of chorioamnionitis and SGA for PAIS, pointing to the importance of inflammatory processes and fetal-placental insufficiency. Multiple birth and preterm birth were additional risk factors. WHAT THIS PAPER ADDS: Chorioamnionitis and small for gestational age (SGA) precede perinatal arterial ischaemic stroke (PAIS). Chorioamnionitis and SGA are independent risk factors for PAIS. Inflammatory processes and fetal-placental insufficiency are the likely underlying mechanisms. Multiple birth and preterm birth are additional risk factors.

[Migraine in childhood and adolescence-neurostimulation as a future innovative approach in terms of a multimodal treatment regimen]. / Migräne im Kindes- und Jugendalter ­ Ausblick auf innovative Behandlungsansätze im Rahmen multimodaler Therapiekonzepte.

Although migraine is a relevant health issue in children and adolescents, clinical care and research are still underrepresented and underfunded in this field. Quality of life can be significantly reduced when living with frequent episodes of pain. Due to the high level of vulnerability of the developing brain during adolescence, the risk of chronification and persistence into adulthood is high. In this narrative review, we describe the corner stones of a patient-centered, multimodular treatment regimen. Further, an update on the pathophysiology of migraine is given considering the concept of a periodically oscillating functional state of the brain in migraine patients ("migraine is a brain state"). Besides central mechanisms, muscular structures with the symptoms of muscular pain, tenderness, or myofascial trigger points play an important role. Against this background, the currently available nonpharmacological and innovative neuromodulating approaches are presented focusing on the method of repetitive peripheral magnetic stimulation.

SACS variants are a relevant cause of autosomal recessive hereditary motor and sensory neuropathy.

Mutations in the SACS gene have been initially reported in a rare autosomal recessive cerebellar ataxia syndrome featuring prominent cerebellar atrophy, spasticity and peripheral neuropathy as well as retinal abnormalities in some cases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, ARSACS). In the past few years, the phenotypic spectrum has broadened, mainly owing to the availability and application of high-throughput genetic testing methods. We identified nine patients (three sib pairs, three singleton cases) with isolated, non-syndromic hereditary motor and sensory neuropathy (HMSN) who carried pathogenic SACS mutations, either in the homozygous or compound heterozygous state. None of the patients displayed spasticity or pyramidal signs. Ataxia, which was noted in only three patients, was consistent with a sensory ataxia. Nerve conduction and nerve biopsy studies showed mixed demyelinating and axonal neuropathy. Brain MRI scans were either normal or revealed isolated upper vermis atrophy of the cerebellum. Our findings confirm the broad clinical spectrum associated with SACS mutations, including pure polyneuropathy without characteristic clinical and brain imaging manifestations of ARSACS.

Benign epilepsy with centrotemporal spikes: Correlating spike frequency and neuropsychology.

OBJECTIVES: Neuropsychological sequelae are a feature of benign epilepsy with centrotemporal spikes (BECTS) in children. A correlation between the frequency of interictal EEG discharges and the cognitive as well as behavioral profile of the patients has been suspected but not proven. MATERIALS AND METHODS: Children with BECTS that had not yet been treated were included into a randomized controlled trial. In the initial visit, EEGs were recorded. The frequency of interictal discharges was quantified. Correlations between the discharge frequency and the performance in a neuropsychological test battery were examined. RESULTS: The cognitive test results were within or slightly above normal range (Culture-free intelligence test: 99.4%-confidence interval [CI]: [50.3, 59.9], test standardized to a population mean of 50). Parent-reported behavioral abnormalities were statistically significantly increased (CBCL total score CI: [51.9, 61.9], population mean as above). Correlations between the frequency of interictal epileptic discharges and the test results could not be identified (lowest encountered P-value: 0.034, not significant after correction for multiple testing). CONCLUSION: The data do not support the hypothesis that the frequency of the interictal EEG discharges influences the neurocognitive performance or behavioral parameters of children with BECTS.

Symptom patterns in childhood arterial ischemic stroke: Analysis of a population-based study in Germany.

HINTERGRUND: Die zeitliche Verzögerung zwischen Symptombeginn und Diagnose ist eine Herausforderung in der Behandlung von Kindern mit arteriell ischämischem Schlaganfall. Frühere Studien zur klinischen Präsentation beschäftigten sich v. a. mit kumulativen Symptomen. ZIELSETZUNG: Ziel dieser Studie ist es, mögliche Symptommuster aufzuzeigen. METHODEN: In einer aktiven Beobachtungsstudie zwischen 01/2015 und 12/2016 (ESPED-Studie) wurden Kinder mit Erstdiagnose eines arteriell ischämischen Schlaganfalls eingeschlossen. Isoliert auftretende Erstsymptome wurden verschiedenen Symptomkombinationen gegenübergestellt. Zudem wurde untersucht, inwieweit ein als "akut" oder "progredient" klassifiziertes Auftreten der Symptome Rückschlüsse auf die zugrundeliegende Ätiologie erlaubt. ERGEBNISSE: Es wurden 99 Kinder in die Studie eingeschlossen. Unabhängig vom Alter traten überwiegend fokale Symptome auf (86%). Krampfanfälle als Initialsymptom wurden insbesondere bei Säuglingen beschrieben (67%), wohin-gegen diffuse, unspezifische Symptome vor allem bei Vorschulkindern (38%) und älteren Kindern (59%) auftraten. Isoliert traten fokale Symptome bei 37 Kindern auf, 48 Kinder zeigten zusätzlich unspezifische Symptome, darunter auch 9 Kinder mit Krampfanfällen. Isolierte unspezifische Symptome zeigten sich lediglich bei 7 Kindern, 2 Kinder wurden nur mit Krampfanfällen symptomatisch. Die Akuität des Symptombeginns wurde bei 53/78 als "akut" und bei "25/78 Fällen als "progredient" klassifiziert, lieferte jedoch keinen Hinweis auf die zugrundeliegende Ätiologie. SCHLUSSFOLGERUNG: Jedes neue fokal neurologische Defizit sollte unabhängig vom Auftreten (isoliert oder kombiniert, akut oder progredient) an einen kindlichen Schlaganfall denken lassen. BACKGROUND: Time delay between onset of clinical symptoms and diagnosis is a challenge in childhood arterial ischemic stroke. Most previous studies reported cumulative symptoms. OBJECTIVE: We attempted to identify typical symptom patterns and assessed their emergence in childhood stroke. METHODS: Prospective active surveillance in ESPED, a hospital based Pediatric Surveillance Unit for rare diseases in Germany, between January 2015 and December 2016. Case definition: first diagnosis of a radiologically confirmed arterial ischemic stroke. Symptom patterns were identified as occurring in isolation or in combination. We distinguished acute vs. progressive onset. We ascertained risk factors to identify the possible etiology. RESULTS: 99 children with childhood arterial ischemic stroke were reported. Focal symptoms were the predominant presenting feature (86%), independent of age. Seizures were more often seen in infants < 1 year (67%), whereas diffuse symptoms were more present in pre-school children (38%) and older children (59%). 37 children had focal features alone and 48 additional non-specific features, including 9 with seizures. Isolated non-specific features accounted for 7 cases, and 2 children had (focal) seizures as the only symptom. In 77% of all cases at least one risk factor was identified. The emergence of symptoms was acute in 53/78 cases and progressive in 25/78 cases. The pattern of emergence was unrelated to the underlying etiology. CONCLUSIONS: Any new focal neurological deficit in isolation, or associated with seizures or further non-specific symptoms should alert to childhood stroke.

Health-Related Quality of Life of Children/Adolescents with Vertigo: Retrospective Study from the German Center of Vertigo and Balance Disorders.

Purpose To assess the impact of vertigo on health-related quality of life (HrQoL) of children/adolescents and to assess if the impact on HrQoL varies by age group, gender, and type of vertigo diagnoses. Methods A retrospective analysis was performed on the clinical and HrQoL data of children and adolescents referred to the German Center of Vertigo and Balance Disorders (n = 32; male = 17; female = 15; age range: 8-18 years), using the KIDSCREEN-52 questionnaire. For each scale, means of the Z-scores with 95% confidence intervals of the study and norm sample were compared. By nonparametric Kruskal-Wallis statistics differences between diagnostic groups were assessed. To assess the gender- and age-specific impact of vertigo on quality of life, Wilcoxon signed-rank test was used. Results The means of the physical well-being, psychological well-being, autonomy scale, and the general HrQoL index of patients were considerably lower than the means of the norm sample. The physical well-being seemed to be most affected by vertigo. The reduction of HrQoL was not related to gender and vertigo types but seemed to be higher in children suffering from vertigo aged 12 to 18 years than children aged 8 to 11 years. Conclusion These are the first data to demonstrate impaired HrQoL in children with chronic vertigo.

Neonatal Arterial Ischemic Stroke - A Hospital Based Active Surveillance Study in Germany.

Background Neonatal arterial ischemic stroke (NAIS) accounts for substantial long term sequelae in children. The potential effectiveness of neuroprotective therapies needs to be evaluated in appropriate studies with sufficient power. Objective To identify annual number of NAIS cases in Germany potentially eligible for randomized interventional trials. Methods Active surveillance for NAIS in 345 pediatric hospitals with questionnaire based validation of reported cases. Results Incidence of NAIS (7.1/100000 births) was in the range of other population-based studies. To design future clinical trials with anticoagulative or regenerative therapies, it is of major importance to distinguish between cases with or without relevant perinatal pathology. Children without underlying disease or premature birth accounted for 56% of all reported NAIS cases (primary NAIS). In 69% of the primary cases clinical seizures were observed. Although 31% showed other, less pathognomonic symptoms, NAIS was diagnosed. Mean time span between onset of symptoms and diagnosis was 2.9 days. The sensitivity of the initial ultrasound performed in all cases was 69%. Conclusions NAIS is a rare but not negligible morbidity in newborns. Asymptomatic children account for 56% of NAIS in all neonates. In these, not only seizures but also other unexplained symptoms should trigger diagnostic work-up with cUS and cMRI. Negative initial ultrasound results do not exclude NAIS.

The Complexity Signature: Developing a Tool to Communicate Biopsychosocial Severity of Disease for Children with Chronic Neurological Complexity.

Aim For children with medical complexity, interdisciplinary treatment approaches are required to address the various aspects defined within the biopsychosocial model. Methods The present study identifies dimensions of the biopsychosocial model to generate a standardized visualized severity score for chronic neurological diseases in children. We demonstrate the score's applicability and usefulness in clinical practice among clinicians with and without pediatric board certification with the aid of illustrative patient cases. The results are compared by Spearman correlation coefficient. Results Nine dimensions were identified as the basis for the development of the score, which consists of five grades of severity for each of the selected neuropediatric subsections. All board-certified pediatricians would recommend the application of the severity score in clinical routine. Furthermore, a good correlation was revealed between direct and indirect (severity score) assessment. Interpretation The severity score developed in this study takes into account biopsychosocial aspects of chronic diseases while being comprehensible and easily applicable in clinical routine-a biopsychosocial signature serving as an excellent, striking communication basis within the interdisciplinary team. However, upcoming studies including more patient cases are needed for further refinement.

Molecular and Phenotypic Characterization of the RORB-Related Disorder.

BACKGROUND AND OBJECTIVES: Heterozygous variants in RAR-related orphan receptor B (RORB) have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with RORB pathogenic variants and to provide arguments in favor of the pathogenicity of variants. METHODS: Through an international collaboration, we analyzed seizure characteristics, EEG data, and genotypes of a cohort of patients with heterozygous variants in RORB. To gain insight into disease mechanisms, we performed ex vivo cortical electroporation in mouse embryos of 5 selected variants, 2 truncating and 3 missense, and evaluated on expression and quantified changes in axonal morphology. RESULTS: We identified 35 patients (17 male, median age 10 years, range 2.5-23 years) carrying 32 different heterozygous variants in RORB, including 28 single-nucleotide variants or small insertions/deletions (12 missense, 12 frameshift or nonsense, 2 splice-site variants, and 2 in-frame deletions), and 4 microdeletions; de novo in 18 patients and inherited in 10. Seizures were reported in 31/35 (89%) patients, with a median age at onset of 3 years (range 4 months-12 years). Absence seizures occurred in 25 patients with epilepsy (81%). Nineteen patients experienced a single seizure type: absences, myoclonic absences, or absences with eyelid myoclonia and focal seizures. Nine patients had absence seizures combined with other generalized seizure types. One patient had presented with absences associated with photosensitive occipital seizures. Three other patients had generalized tonic-clonic seizures without absences. ID of variable degree was observed in 85% of the patients. Expression studies in cultured neurons showed shorter axons for the 5 tested variants, both truncating and missense variants, supporting an impaired protein function. DISCUSSION: In most patients, the phenotype of the RORB-related disorder associates absence seizures with mild-to-moderate ID. In silico and in vitro evaluation of the variants in our cohort, including axonal morphogenetic experiments in cultured neurons, supports their pathogenicity, showing a hypomorphic effect.

Three-dimensional analysis of positional plagiocephaly before and after molding helmet therapy in comparison to normal head growth.

OBJECTIVE: Stereophotogrammetry enables a simple and radiation free longitudinal analysis of skull asymmetries: in a three-dimensional coordinate system various distances (length, breadth, cephalic index, oblique diameters, ear shift, head circumference) can be analyzed. We also defined separate volume sections in order to further quantify the degree of asymmetry in the posterior and anterior components of both sides of the head. PATIENTS AND METHODS: In 51 infants (mean age, 6 months; SD 0.97) with positional plagiocephaly, we determined these parameters at the beginning as well as at the end of molding helmet therapy (mean therapy time 4.9 months). Thirty-seven infants without positional deformity (mean age, 6.4 months; SD 0.3) served as control group and provided data about what appears to be normal and how these parameters change during growth over a comparable period of time. RESULTS: Compared with the control group, the plagiocephalic heads were more brachycephalic, but closely approximated the normal shape under molding therapy. The striking volume difference between the left and right posterior sections in the plagiocephalic children (the mean volume of the flattened side being 21% smaller than the one on the contralateral side) improved as well (to a residual difference of mean 8%) and ended up with a value close to the control group (mean 6%). CONCLUSION: There is a broad clinical application area for stereophotogrammetry analyzing skull morphology: In plagiocephalic infants we demonstrate impressive changes of head shape under molding therapy; in normal-looking infants we describe the extent of unperceived asymmetry.

Effects of a reduction of the number of electrodes in the EEG montage on the number of identified seizure patterns.

Continuous EEG monitoring (cEEG) is frequently used in neurocritical care. The detection of seizures is one of the main objectives. The placement of the EEG electrodes is time consuming, therefore a reduced montage might lead to an increased availability in the ICU setting. It is unknown whether such a reduction of electrodes reduces the number of seizure patterns that are detected. A total of 95 seizure and 95 control EEG sequences from a pediatric epilepsy monitoring unit (EMU) were anonymized and reduced to an eight-lead montage. Two experts evaluated the recordings and the seizure detection rates using the reduced and the full montage were compared. Sensitivity and specificity for the seizure detection were calculated using the original EMU findings as gold standard. The sensitivity to detect seizures was 0.65 for the reduced montage compared to 0.76 for the full montage (p = 0.031). The specificities (0.97 and 0.96) were comparable (p = 1). A total of 4/9 (44%) of the generalized, 12/44 (27%) of the frontal, 6/14 (43%) of the central, 0/1 (0%) of the occipital, 6/20 (30%) of the temporal, and 5/7 (71%) of the parietal seizure patterns were not detected using the reduced montage. The median time difference between the onset of the seizure pattern in the full and reduced montage was 0.026s (IQR 5.651s). In this study the reduction of the EEG montage from 21 to eight electrodes reduced the sensitivity to detect seizure patterns from 0.76 to 0.65. The specificity remained virtually unchanged.

Cognitive profiles in pediatric unilobar vs. multilobar epilepsy.

OBJECTIVES: We aimed to determine how cognitive impairment relates to the extent of the presumed epileptogenic zone in pediatric focal epilepsies. We analyzed the cognitive functions in unilobar compared to multilobar focal epilepsy patients that underwent neuropsychological testing at a tertiary epilepsy center. METHODS: We assessed cognitive functions of pediatric focal epilepsy patients with the German version of the Wechsler Intelligence Scales that measures full-scale IQ and subcategories. We assessed differences in IQ and epilepsy-related variables between unilobar and multilobar epilepsy patients. RESULTS: We included 62 patients (37 unilobar, 25 multilobar), aged 10.6 ± 3.7 years. Full-scale IQ values were significantly higher in unilobar (93.6 ± 17.7, 95% CI 87.7-99.6) than in multilobar epilepsy patients (77.3 ± 17.2, 95% CI 69.3-85.0; p = 0.001). In all but one IQ subcategory (working memory), significantly higher values were measured in unilobar than in multilobar epilepsy patients. The proportion of unilobar epilepsy patients with severe cognitive impairment (8.3%) and below-average intelligence (30.5%) was lower compared to multilobar epilepsy patients (47.6% and 61.9%; p = 0.002 and p = 0.021, respectively). Epilepsy onset occurred earlier in multilobar (4.0 years, 95% CI 2.6-5.5, SD ± 3.4 years) than in unilobar epilepsy patients (7.0 years, 95% CI 5.5-8.5, SD ± 4.4 years, p = 0.008). CONCLUSIONS: Pediatric multilobar epilepsy patients face more cognitive issues than unilobar epilepsy patients on average. Our findings should help to identify children and adolescents who are most at risk for impaired cognitive development. A limitation of our study is the simple division into unilobar and multilobar epilepsies, with no specific account being taken of etiology/epilepsy syndrome, which can have a profound effect on cognition.