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Objective This study aimed to measure health-related quality of life (HRQOL) in children and adolescents with tuberous sclerosis complex (TSC) and quality of life (QOL) and depressive symptoms among caregivers. Methods Adequate metrics were used to assess HRQOL in children and adolescents with TSC (4-18 years, KINDLR) as well as QOL (EQ-5D) and symptoms of depression (BDI-II) among caregivers. Predictors for reduced HRQOL and depressive symptoms were identified by variance analysis, ordinal regression, and bivariate correlation. Results The mean HRQOL score was 67.9 ± 12.7, and significantly lower values were associated with increasing age, attending special needs education, TSC-associated psychiatric symptoms, and drug-related adverse events. The mean QOL of caregivers was 85.4 ± 15.7, and caregiver's sex, TSC mutation locus, familial TSC clustering, special needs education, degree of disability, care dependency, presence of TSC-associated psychiatric symptoms, and TSC severity were significant predictors of lower QOL. Depressive symptoms were identified in 45.7% of caregivers, associated with female sex of the caregiver, familial TSC clustering, special needs education, and presence of TSC-associated psychiatric symptoms of the child. Multivariate regression analysis revealed adolescence and drug-related adverse events as significant predictors for lower HRQOL in TSC children, and TSC2 variants predicted lower QOL and depressive symptoms in caregivers. Conclusion Compared with other chronic diseases, such as headache, diabetes or obesity, children with TSC have significantly lower HRQOL, which further decreases during adolescence. A decreased HRQOL of patients correlates with a lower QOL and increased symptoms of depression of their caregivers. These results may improve the comprehensive therapy and care of children and adolescents with TSC and their families and caregivers. Trial registration DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

Objective This study was undertaken to evaluate the long-term efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. Methods A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021. Results Long-term data for 262 patients (mean age = 40 years, range = 5-81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients had never received levetiracetam (LEV), whereas 133 (50.8%) were switched from LEV. The length of BRV exposure ranged from 1 day to 5 years, with a median retention time of 1.6 years, resulting in a total BRV exposure time of 6829 months (569 years). The retention rate was 61.1% at 12 months, with a reported efficacy of 33.1% (79/239; 50% responder rate, 23 patients lost-to-follow-up), including 10.9% reported as seizure-free. The retention rate for the entire study period was 50.8%, and at last follow-up, 133 patients were receiving BRV at a mean dose of 222 ± 104 mg (median = 200, range = 25-400), including 52 (39.1%) who exceeded the recommended upper dose of 200 mg. Fewer concomitant antiseizure medications and switching from LEV to BRV correlated with better short-term responses, but no investigated parameters correlated with positive long-term outcomes. BRV was discontinued in 63 (24%) patients due to insufficient efficacy, in 29 (11%) for psychobehavioral adverse events, in 25 (10%) for other adverse events, and in 24 (9%) for other reasons. Significance BRV showed a clinically useful 50% responder rate of 33% at 12 months and overall retention of >50%, despite 90% of included patients having previous LEV exposure. BRV was well tolerated; however, psychobehavioral adverse events occurred in one out of 10 patients. Although we identified short-term response and retention predictors, we could not identify significant predictors for long-term outcomes.

Efficient cooling of the thermally extremely loaded high-pressure-turbine blades and vanes is required to ensure acceptable service life. The development of cooling systems is a high-dimensional problem, since it includes multiple design parameters. The integration of stochastic methods into the design phase contributes to a better understanding of the complex interaction between the design parameters and the system behavior and thus helps designing more efficient cooling systems. Therefore, the present study compares two stochastic methods, the Elementary-Effect method by Morris and the Coefficient-of-Importance, for the quantification of the sensitivity of the cooling flow to geometric variations using a 1D flow network of a high-pressure-turbine blade. As test case a multipass cooling system with rib-roughened walls is investigated. To achieve geometrically meaningful variations a new parametrization, called Harmonic-Spline-Deformation, is developed and first time presented in the paper at hand. The parametrization proves to be universally applicable to the components of a cooling system and facilitates the interpretation of the physical relationships between variables and resulting system behavior. For a sufficiently large population size, both methods show good agreement in quantifying the importance of design parameters regarding their effect on the cooling flow. The Coefficient-of-Importance, however, proves to be more stable against a decreasing population size and more robust against defects in the population.

Two siblings with an early onset of a neurodegenerative disease were presented with muscular hypotonia, secondary microcephaly, and severe developmental delay. Seizures were refractory to treatment but could be controlled with a ketogenic diet. Over the course of 5 years, whole exome sequencing (WES) was performed twice in both children. The first time the diagnosis was missed. The next one revealed compound heterozygous mutations in the gene coding for the tubulin folding cofactor D. Technical improvements in WES mandated a new investigation after a few years in children where the diagnosis has not been found.

The engine-cycle performance of jet engines can be improved by more efficient cooling systems, either by reducing the required cooling air or by intensifying the cooling efficiency with the same amount of cooling mass flow. However, the multitude of geometrical design parameters and the strong multidisciplinary aspect of cooling mass flow consumption optimization make designing the cooling systems extremely challenging. Integrating probabilistic methods into the thermal design process enables the automated evaluation of multiple design variants which contributes to the development of more efficient systems. In the present study, the sensitivity of a multi-pass cooling system to geometric variations is investigated. The cooling air flow, solved using a 1D, correlation based flow solver, is iteratively coupled with the 3D-FE thermo-mechanical analysis of the blade. The geometry of the cooling system is varied using the Harmonic-Spline-Deformation parametric, which has been extended to modify the wall thickness enabling to perform a geometrical-holistic analysis. Furthermore, the Elementary-Effects-Method (EEM) and the Monte-Carlo-Simulation (MCS) are compared to identify the most influential parameters and analyze their complex interactions. It is shown that the cooling system’s performance is mostly affected by the shape and position of the first web. Furthermore, MCS proves to be robust towards changes in design space while simultaneously enabling a more detailed analysis of the system behavior compared to EEM.

West syndrome is an epilepsy syndrome characterized by repetitive epileptic spasms (ES) and hypsarrhythmia, typically leading to developmental delay/intellectual disability (DD/ID). It is considered a classic epileptic encephalopathy (EE). We designed a diagnostic sequencing panel targeting 131 genes associated with epilepsy and/or EE and screened a cohort of 45 individuals with clinical diagnosis of West syndrome. We identified disease-causing single nucleotide variants in 11 out of 45 individuals affecting genes commonly associated with West syndrome (such as CDKL5, ARX) but also in genes predominantly linked to other epileptic disorders (such as DEPDC5, SCN1A, WDR45, AARS). Panel analysis revealed copy number variants in two additional cases, comprising a 6,7 Mb Duplication on chromosome 2 including SCN2A and SCN3A and a supernumerary marker chromosome 15 leading to an overall diagnostic yield of 29% (13/45). In our cohort, individuals with a disease-causing variant had significantly more severe phenotypes with respect to DD/ID, therapy resistant epilepsy and cerebral atrophy compared to genetically unclarified cases. In addition to investigating the genotypic spectrum of West syndrome, we compared the phenotypic spectrum of clarified versus unclarified cases. Our study illustrates that West syndrome is an electroclinical syndrome caused by various genetic disorders. Individuals without detectable genetic cause might have less encephalopathy leading to a less severe course.

The increasing demands on jet engines require progressive thermodynamic process parameters, which typically lead to higher aerothermal loadings and accordingly to designs with high complexity. State-of-the-art high-pressure turbine (HPT) nozzle guide vane (NGV) design involves vane profiles with three-dimensional features including a high amount of film cooling and profiled endwalls (PEWs). Typically, the specific mass flow, also called capacity, which governs the engine's operation, is set by the HPT NGV. Hence, geometric variations due to manufacturing scatter of the HPT NGV's passage can affect relevant aerodynamic quantities and the entire engine behavior. Within the traditional deterministic design approach, the influences of those geometric variations are covered by conservative assumptions and engineering experience. This paper addresses the consideration of variability due to the manufacturing of HPT NGVs through probabilistic CFD investigations. To establish a statistical database, 80 HPT NGVs are digitized with a high precision optical 3D scanning system to record the outer geometry. The vane profiles are parametrized by a section-based approach. For this purpose, traditional profile theory is combined with a novel method that enables the description of NGV profile variability taking the particular leading edge (LE) shape into account. Furthermore, the geometric variability of PEWs is incorporated by means of principle component analysis (PCA). On this basis, a probabilistic system assessment including a sensitivity analysis in terms of capacity and total pressure loss coefficient is realized. Sampling-based methods are applied to conduct a variety of 3D CFD simulations for a typical population of profile and endwall geometries. This probabilistic investigation using realistic input parameter distributions and correlations contributes to a robust NGV design in terms of relevant aerodynamic quantities.

OBJECTIVE To compare direct and indirect costs and quality of life (QoL) of pediatric and adult patients with Dravet syndrome (DS), with drug-resistant epilepsy (DRE) and in seizure remission (SR), and their caregivers, in Germany. METHODS Questionnaire responses from 93 DS patients and their caregivers were matched by age and gender with responses from 93 DRE and 93 SR patients collected in independent studies, and were compared across main components of QoL, direct costs (patient visits, medication use, care level, medical equipment, and ancillary treatments), and indirect costs (quitting job, reduced working hours, missed days). RESULTS Mean total direct costs were highest for DS patients (€4864 [median €3564] vs €3049 [median €1506] for DRE [excluding outliers], P = 0.01; and €1007 [median €311], P

The increasing demands on jet engines require progressive thermodynamic process parameters, which typically lead to higher aerothermal loadings and accordingly to designs with high complexity. State of the art high pressure turbine (HPT) nozzle guide vane (NGV) design involves vane profiles with three-dimensional features including a high amount of film cooling and profiled endwalls (PEW). Typically, the specific massflow, also called capacity, which governs the engine’s operation, is set by the HPT NGV. Hence, geometric variations due to manufacturing scatter of the HPT NGV’s passage can affect relevant aerodynamic quantities and the entire engine behavior. Within the traditional deterministic design approach, the influences of those geometric variations are covered by conservative assumptions and engineering experience. This paper addresses the consideration of variability due to manufacturing of HPT NGVs through probabilistic CFD investigations. In order to establish a statistical database, 80 HPT NGVs are digitized with a high precision optical 3D scanning system to record the outer geometry. The vane profiles are parametrized by a section based approach. For this purpose, traditional profile theory is combined with a novel method that enables the description of NGV profile variability taking the particular leading edge (LE) shape into account. Furthermore, the geometric variability of PEWs is incorporated by means of principle component analysis (PCA). On this basis, a probabilistic system assessment including a sensitivity analysis in terms of capacity and total pressure loss coefficient is realized. Sampling-based methods are applied in order to conduct a variety of 3D CFD simulations for a typical population of profile and endwall geometries. This probabilistic investigation using realistic input parameter distributions and correlations contributes to a robust NGV design in terms of relevant aerodynamic quantities.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the central nervous system and preferentially targets the optic nerves and spinal cord. NMO is rare in children and clinical course of the disease is highly variable as described in studies. Here, we present a case report of a young girl presenting with a rare course of pediatric NMO with an early disease onset at the age of 12 years, a relapse free interval of 4 years, evidence of NMO immunoglobulin G (IgG) and an unusual response against immunosuppressive therapy. The aim of this report is to highlight the potentially long remission period between relapses complicating proper diagnosis despite well defined diagnostic criteria. In addition, we want to encourage the use of rituximab in pediatric NMO, although larger cohorts are warranted to establish B cell depleting therapies in juvenile NMO.

OBJECTIVE: This article aims to report the first clinical experiences concerning effectiveness and tolerability of perampanel (PER) in a pediatric population with refractory epilepsies.PATIENTS AND METHODS: This nonsponsored, observational, retrospective survey was conducted through collaboration with multiple centers in Europe. The clinical course of the first pediatric patients treated in these centers with PER was documented with the help of a questionnaire completed by the treating physicians. Effectiveness and adverse effects were evaluated. The study population consisted of 58 patients (mean age, 10.5 years; range, 2-17 years), suffering from various refractory epilepsies, classified as focal epilepsy (n = 36), unclassified generalized epilepsy (n = 12), Lennox-Gastaut syndrome (n = 5), West syndrome (n = 3), and Dravet syndrome (n = 2).RESULTS: The response rate (≥ 50% seizure reduction) after the first 3 months of therapy was 31% (18/58 patients) in total. Complete seizure control was achieved in five patients (9% overall). Aggravation of seizures occurred in five cases (9%). The most frequently occurring adverse effects were reduced vigilance or fatigue (n = 16) and behavioral changes (n = 14).DISCUSSION: PER seems to be effective also in children and adolescents with pharmaco-refractory epilepsies. Tolerability was acceptable.

Der Zusammenhang zwischen Schlaf und Epilepsie wurde schon in der Antike beobachtet. So beschrieb schon Aristoteles, dass Epilepsien bzw. epileptische Anfälle häufig während des Schlafes aufträten (1).

SLC39A8 deficiency is a severe inborn error of metabolism that is caused by impaired function of manganese metabolism in humans. Mutations in SLC39A8 lead to impaired function of the manganese transporter ZIP8 and thus manganese deficiency. Due to the important role of Mn2+ as a cofactor for a variety of enzymes, the resulting phenotype is complex and severe. The manganese-dependence of β-1,4-galactosyltransferases leads to secondary hypoglycosylation, making SLC39A8 deficiency both a disorder of trace element metabolism and a congenital disorder of glycosylation. Some hypoglycosylation disorders have previously been treated with galactose administration. The development of an effective treatment of the disorder by high-dose manganese substitution aims at correcting biochemical, and hopefully, clinical abnormalities. Two SCL39A8 deficient patients were treated with 15 and 20 mg MnSO4/kg bodyweight per day. Glycosylation and blood manganese were monitored closely. In addition, magnetic resonance imaging was performed to detect potential toxic effects of manganese. All measured enzyme dysfunctions resolved completely and considerable clinical improvement regarding motor abilities, hearing, and other neurological manifestations was observed. High-dose manganese substitution was effective in two patients with SLC39A8 deficiency. Close therapy monitoring by glycosylation assays and blood manganese measurements is necessary to prevent manganese toxicity.

Isolated optic neuritis in adults (ON) is the most common initial manifestation of multiple sclerosis (MS). Conversion to MS after childhood ON is not well determined. We aimed to identify risk factors predicting MS following ON and to develop risk profiles with adjusted clinical follow-up based on current diagnostic tools. Medical records of 42 cases with isolated ON between 1970 and 2005 were analysed. In 2006 and 2007 all patients received a clinical follow-up investigation including ophthalmological and neurological examination, visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) and cerebral magnetic resonance imaging (cMRI). Investigation was performed to a mean follow-up of 18 years (3-38 years). 14% of all patients showed MS-like lesions in cMRI. Additional neurologic symptoms or abnormal cMRI at initial presentation indicating dissemination in space significantly altered the risk of MS (OR 16.0, 95% CI [1.5; 176.5], p = 0.020), (OR 4.6, 95% CI [0.7; 31.0], respectively). Severe visual loss and funduscopic affection reduced the likelihood for progression to MS (OR 0.2, 95% CI [0.0; 1.5]). Children presenting with isolated ON, neurological impairment at onset or especially coordinative dysfunction at follow-up and demyelinating lesions in cMRI at disease onset were at high risk for the development of MS.

We report a ventriculoperitoneal shunt infection associated with Kytococcus schroeteri, a Gram-positive bacterium from the family Dermacoccaceae. While the biochemical identification systems do not reliably identify this potential pathogen, sequence-based identification is recommended to guide the antibiotic treatment of this intrinsically meticillin-resistant species, which is susceptible to vancomycin, gentamicin and/or rifampicin.

Background: Optic neuritis (ON) is identified as one of the most frequent potential risk factor associated with future multiple sclerosis (MS). In children, conversion to MS after isolated ON is lower than in adults. Here, we aim to identify cerebrospinal fluid (CSF) and peripheral blood (PB) cell composition and cell activation status as potential biomarkers to distinguish children with isolated ON from children at high risk for MS. Methods: Thirty patients were identified with ON (9), clinically isolated syndrome (CIS, 5), or pediatric MS (16) and first compared with age-matched healthy controls (12) and second to adult patients with MS (33), CIS (10), or isolated ON (17). All patients received intravenous cortisone pulse therapy at least 5 days (1,000 mg/d). CSF was taken prior to cortisone therapy. All MS patients were treatment naive. Results: CSF analysis revealed positive oligoclonal bands (OCB) in 15 of 16 MS children; none of the CIS patients show OCBs, whereas 4 of 9 children with ON expose OCBs. FACS analysis demonstrated elevated plasma cells in CSF both in children and adult MS patients and revealed high proportion of CD4+-T-cells in pediatric MS patients compared with childhood isolated ON. In contrast, proportion of CD8+-T-cells in PB in ON patients was elevated compared with the MS cohort. CSF results of children with CIS conduct completely different from that of adults. Conclusion: FACS analysis and T cell activation could be assumed as predictive parameter, distinguishing isolated ON from CIS or pediatric MS. CIS is supposed to show a different clinical disease course in children compared with adults.

To analyse cerebrospinal fluid (CSF) hydrodynamics in patients with Chiari type I malformation (CM) with and without syringomyelia using 4D magnetic resonance (MR) phase contrast (PC) flow imaging. 4D-PC CSF flow data were acquired in 20 patients with CM (12 patients with presyrinx/syrinx). Characteristic 4D-CSF flow patterns were identified. Quantitative CSF flow parameters were assessed at the craniocervical junction and the cervical spinal canal and compared with healthy volunteers and between patients with and without syringomyelia. Compared with healthy volunteers, 17 CM patients showed flow abnormalities at the craniocervical junction in the form of heterogeneous flow (n = 3), anterolateral flow jets (n = 14) and flow vortex formation (n = 5), most prevalent in patients with syringomyelia. Peak flow velocities at the craniocervical junction were significantly increased in patients (−15.5 ± 11.3 vs. −4.7 ± 0.7 cm/s in healthy volunteers, P

To evaluate the applicability of 4D phase contrast (4D PC) MR imaging in the assessment of cerebrospinal fluid dynamics in healthy volunteers and patients with lesions at the craniocervical junction or the cervical spinal canal.Ten healthy volunteers and four patients with lesions including Chiari I malformation and cervical canal stenoses were examined by a cardiac-gated 4D PC imaging sequence on 1.5T MRI. Phase contrast images were postprocessed allowing for flow quantification and flow pathline visualisation. Velocity data were compared with conventional axial 2D phase contrast images.The 4D PC sequence allowed for flow quantification and visualisation in all individuals. Bland-Altman analysis showed good agreement of 2D and 4D PC velocity data. In healthy volunteers, CSF flow was homogeneously distributed in the anterior and anterolateral subarachnoid space with the flow directed caudally during systole and cranially during diastole. Flow velocities were closely related to the width of the subarachnoid space. Patients showed grossly altered CSF flow patterns with formation of flow jets with increased flow velocities.4D PC MR imaging allows for a detailed assessment of CSF flow dynamics helping to distinguish physiological from complex pathological flow patterns at the craniocervical junction and the cervical spine.

Previous studies have indicated a male predominance in pediatric stroke. To elucidate this gender disparity, total testosterone concentration was measured in children with arterial ischemic stroke (AIS; n = 72), children with cerebral sinovenous thrombosis (CSVT; n = 52), and 109 healthy controls. Testosterone levels above the 90th percentile for age and gender were documented in 10 children with AIS (13.9%) and 10 with CSVT (19.2%), totaling 16.7% of patients with cerebral thromboembolism overall, as compared with only 2 of 109 controls (1.8%; p = 0.002). In multivariate analysis with adjustment for total cholesterol level, hematocrit, and pubertal status, elevated testosterone was independently associated with increased disease risk (odds ratio [95% confidence interval]: overall = 3.98 [1.38-11.45]; AIS = 3.88 [1.13-13.35]; CSVT = 5.50 [1.65-18.32]). Further adjusted analyses revealed that, for each 1nmol/l increase in testosterone in boys, the odds of cerebral thromboembolism were increased 1.3-fold.

Objective: To explore the involvement of M-type potassium channels KCNQ2 , Q3 , and Q5 in the pathogenesis of common idiopathic epilepsies. Methods: Sequence analysis of the KCNQ2 , Q3 , and Q5 coding regions was performed in a screening sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an association study was conducted for all discovered variants in a case–control sample comprising 459 German patients with idiopathic generalized epilepsy (IGE) and 462 population controls. Results: An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of families with rolandic epilepsy without neonatal seizures discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium current amplitude in Xenopus oocytes and was present only once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were present in all affected family members and did not occur in controls, but did not show obvious functional abnormalities. The KCNQ3 missense variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls ( p = 0.008). In KCNQ2 , a silent single nucleotide polymorphism (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004). Conclusion: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes. GLOSSARY: BNFC = benign neonatal familial convulsions; bp = base pair; cRNA = complementary RNA; IAE = idiopathic absence epilepsy; IE = idiopathic epilepsy; IGE = idiopathic generalized epilepsy; JME = juvenile myoclonic epilepsy; OR = odds ratio; RE = rolandic epilepsy; SNP = single nucleotide polymorphism; WT = wild type.

Brain tumors are the most common solid tumor entity in childhood. Symptoms are often unspecific, depending not only on the localization of the tumor, but also on the age of the child. The aim of this study was to detect factors influencing the time span between the occurrence of symptoms and the diagnosis to alert health professionals to the early symptoms of pediatric brain tumors. The records of 245 consecutive patients treated for brain tumors between 1980 and 2004 at the neuropediatric department of the University of Muenster were analyzed regarding their primary symptoms, tumor location, entity, and, in 151 cases, the primary electroencephalogram findings. The median time span between symptom onset and diagnosis in our study was 24 days. Multivariate analysis showed a significant influence of 6 parameters on the interval between symptom onset and diagnosis. An additional symptom had a significant influence on the time span between symptom onset and diagnosis in the univariate analysis. The findings that several symptoms influence the interval between symptom onset and diagnosis emphasize the necessity to systematically inquire about the key symptoms of brain tumors. The challenge for every consultant is to decide in which cases cerebral imaging is appropriate. As the most frequent symptoms are unspecific and often underestimated, a detailed anamnesis is crucial to detect possible brain tumor patients. In doubtful cases, a systematic interrogation regarding the catalogue of symptoms can be helpful.

SLC39A8 is a membrane transporter responsible for manganese uptake into the cell. Via whole-exome sequencing, we studied a child that presented with cranial asymmetry, severe infantile spasms with hypsarrhythmia, and dysproportionate dwarfism. Analysis of transferrin glycosylation revealed severe dysglycosylation corresponding to a type II congenital disorder of glycosylation (CDG) and the blood manganese levels were below the detection limit. The variants c.112G>C (p.Gly38Arg) and c.1019T>A (p.Ile340Asn) were identified in SLC39A8. A second individual with the variants c.97G>A (p.Val33Met) and c.1004G>C (p.Ser335Thr) on the paternal allele and c.610G>T (p.Gly204Cys) on the maternal allele was identified among a group of unresolved case subjects with CDG. These data demonstrate that variants in SLC39A8 impair the function of manganese-dependent enzymes, most notably β-1,4-galactosyltransferase, a Golgi enzyme essential for biosynthesis of the carbohydrate part of glycoproteins. Impaired galactosylation leads to a severe disorder with deformed skull, severe seizures, short limbs, profound psychomotor retardation, and hearing loss. Oral galactose supplementation is a treatment option and results in complete normalization of glycosylation. SLC39A8 deficiency links a trace element deficiency with inherited glycosylation disorders.

Sensory gating refers to the ability of the brain to inhibit irrelevant sensory input. In several studies, a pathogenic role of the CHRNA7 gene and the CHRNA7-like gene, respectively, is suggested. In linkage analysis concerning familial centrotemporal spikes and sharp waves (CTS) and benign rolandic epilepsy, evidence for linkage was found to a region on chromosome 15q14, close to the alpha-7 subunit gene of the neuronal nicotinic acetylcholine receptor (CHRNA7). According to these findings, P50 evoked potentials to paired click stimuli were studied in 13 children with CTS in the EEG to determine whether they had normal sensory gating. The control group consisted of 13 healthy probands matched for gender and age. Children with CTS showed a significant sensory gating deficit (p=0.001). These results (1) suggest an inhibitory deficit in early pre-attentive auditory sensory processing in children with CTS and (2) confirm the assumption of a cholinergic pathology in CTS.

Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy -- including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI -- mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a missense mutation in the conserved pore region (40736 C --> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.

Pineal secretion of melatonin, a potential sleep-inducing agent, is stimulated by nighttime darkness. To gain better insight into the control of melatonin physiology in man, we studied melatonin concentrations in ventricular cerebrospinal fluid (v-CSF). In four patients aged 1–4 yr with therapeutic v-CSF drainage, including one with lumbar CSF (l-CSF) drainage, CSF samples were collected sequentially over 24-hr periods. One further patient with severe sleep disturbance had one collection period under chloral hydrate and another after oral melatonin administration. Reduction of light intensity or night periods, respectively, led to increased melatonin levels. At the moment of falling asleep, additional melatonin peaks were observed in v-CSF but not in l-CSF. Oral melatonin, but not chloral hydrate, caused a rapid increase in CSF melatonin between 10 and 80 min after intake, raising levels far beyond physiological concentrations. The commencement of sleep is associated with an additional melatonin peak v-CSF which is independent of baseline secretion during the day–night cycle. The possibility is discussed that the induction of sleep might depend on a critical level or increased melatonin concentrations, which can be achieved with orally administered melatonin.

Background: Every year approximately 280,000 people suffer from traumatic brain injury in Germany. About 72,000 children and adolescents are affected, which is a very high proportion. The majority of patients with traumatic brain injury (TBI) suffer from permanent disabilities as a consequence of this injury. The likelihood of experiencing a TBI is twice as high for boys than for girls. This gender difference becomes more marked with increasing age, presumably due to the gender-specific propensity to risk taking in sports and leisure activities. Whether or not gender-specific factors also influence the outcome regarding mortality and neurocognitive functions or rehabilitation potential has not yet been adequately investigated in Germany. In emergency care, there are also deficits in the coordination of processes across all sectors and in secondary treatment (e.g., by general practitioners and in [early] rehabilitation) which leads to duplication of examinations and treatment. There is currently a lack of systematic documentation of individual cases of medium and severe TBI on different levels of care. Method: Detailed data on accident mechanism, lesions, laboratory parameters and functional deficits and their course are recorded anonymously and analyzed in the TBI Register of the University Clinic Munster in cooperation with partners from the Emergency Medical Care (UKM), Early Rehabilitation (Clemenshospital Munster), continued rehabilitation (Helios Clinic Hattingen), and coordinators of aftercare (Centre for out-patient rehabilitation Munster, Pediatric Neurological Aid, Sociopediatric Centres, NRW). The project is funded by the Ministry for Health, Equality, Care, and Aging of the State of North-Rhine Westphalia as part of the “IuK & Gender Med. NRW” competition. Objectives: Analysis of register data are of prime importance for the evaluation of prevention measures and provides an information basis for optimizing patient care. The structure and process quality along the existing treatment chain including interfaces between emergency treatment and rehabilitation facilities and secondary care are mapped to optimize the quality of TBI patient care.