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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.

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.

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.

CSF protein levels are altered in neurological disorders, such as hydrocephalus of different etiologies. In this retrospective observational study, we analyzed cerebrospinal fluid (CSF) samples in hydrocephalic diseases such as aqueductal stenosis (AQS, n = 27), normal pressure hydrocephalus (NPH, n = 24), hydrocephalus communicans (commHC, n = 25) and idiopathic intracranial hypertension (IIH)/pseudotumor cerebri (PC, n = 7) in comparison with neurological patients without hydrocephalic configuration (control, n = 95). CSF was obtained through CSF diversion procedures and lumbar punction and analyzed for protein concentrations according to the institution’s laboratory standards. We found significantly decreased CSF protein levels in patients suffering from AQS (0.13 mg/dL [0.1–0.16 mg/dL] p = 2.28 × 10−8) and from PC (0.18 mg/dL [0.12–0.24 mg/dL] p = 0.01) compared with controls (0.34 mg/dL [0.33–0.35 mg/dL]). Protein levels were not altered in patients suffering from commHC and NPH compared with neurologically healthy individuals. We propose that a decrease in CSF protein levels is part of an active counterregulatory mechanism to lower CSF volume and, subsequently, intracranial pressure in specific diseases. Research regarding said mechanism and more specific proteomic research on a cellular level must still be performed to prove this hypothesis. Differences in protein levels between different diseases point to different etiologies and mechanisms in different hydrocephalic pathologies.

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.

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.

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.

ZusammenfassungFür die Diagnostik von Epilepsien im Kindes- und Jugendalter und deren Behandlung mit Antikonvulsiva ist Expertise in unterschiedlichen Bereichen nötig. Der Patient profitiert dabei vom Zusammenwirken verschiedener Berufsgruppen. Risiken müssen reduziert und die in klinischen Studien gezeigte Wirksamkeit auch in eine möglichst gute Effektivität unter Routinebedingungen umgesetzt werden. Dabei sollten zunächst Aspekte der Arzneimittelverschreibung durch den Arzt berücksichtigt werden, wie etwa die Auswahl, Kombination und Dosierung der Antikonvulsiva. Dabei sollte die Arzneimittelanwendung nicht vergessen werden. Erst, wenn ein Antikonvulsivum richtig angewendet wird, kann der vom verordnenden Arzt gewünschte Therapieerfolg auch erreicht werden. Dabei sollten sich Maßnahmen nicht nur auf den Pflegedienst, sondern auch auf die Eltern, die Kinder und Jugendlichen selbst sowie Betreuer in Schulen und Kindertageseinrichtungen erstrecken. Durch theoretische Schulungen, praktische Übungen und regelmäßige Einbindung von Apothekern ins interdisziplinäre Behandlungsteam wird vermeidbaren arzneimittelbezogenen Problemen, die zu mangelnder Effektivität und dem Auftreten erhöhter Risiken führen können, vorgebeugt. Auf diese Weise wird nicht nur die Arzneimittel(therapie)sicherheit qualitativ verbessert, sondern auch die Teilhabe und Lebensqualität der Patienten und deren Familien positiv beeinflusst.

Seizure disorder and developmental disorder are two of the most common chronic disorders in childhood. Data on perceived parental burden and specific effects on daily life is scarce. We performed a structured interview, consecutively talking to all parents of pediatric outpatients of our university hospital diagnosed with seizure or developmental disorder. Three hundred seven parents (of 317 affected children: 53 with seizure disorder, 44 with specific developmental disorder, 35 with learning disorder, 71 with intellectual disability, 15 with seizure + specific developmental disorder, 23 with seizure + learning disorder, 76 with seizure disorder + intellectual disability) were interviewed. Parents of children with both seizure disorder and intellectual disability stated the highest constraints in daily life, regarding friends, hobbies, emotional pressure, occupation, partnership, habitation, and financial burden. Due to diagnosis of seizure or developmental disorder, 155/307 (51%) parents reduced their working hours/stopped working, 62/307 (20%) changed their habitation, and 46/307 (15%) broke up. As judged by parents, 148/317 (47%) children are being discriminated against, even own family/friends and educators are held responsible.Parents perceive changes in their daily life and discrimination of their children due to their children's seizure and developmental disorders. An intellectual disability combined with seizure disorder caused the highest constraint. What is Known: • Seizure and/or developmental disorders of children may adversely influence quality of life for affected parents. • Caring for a child with special health care needs can take complete attention and own parental needs may therefore be difficult to meet. What is New: • Two out of three parents stated changes of their daily life such as quitting work, change of habitation, or breakup of partnership due to their child's diagnosis. • As judged by the parents, one in two children with developmental disorder of any kind is being discriminated against, even teachers and own family are held responsible.

Introduction The ciliopathy "Joubert syndrome" was first described in 1969 by Dr. Marie Joubert and most subtypes follow an autosomal recessive inheritance. The complex disorder shows typical clinical features, such as hyperventilation, abnormal eye movements, and retardation. A pathognomonic midbrain-hindbrain malformation, the molar tooth sign, can be found on magnetic resonance imaging of the brainstem. There are a little more than 200 reports of Joubert syndrome in the literature. Case presentation We report a case of a 9-year-old boy who developed a progressive hydrocephalus starting from the age of 4. He underwent VP shunt placement at 8 years, which relieved hydrocephalus-related clinical symptoms and put development of the macrocephalus to a halt. Conclusion Neonatal hydrocephalus due to the altered anatomy of the posterior fossa has been reported earlier, but to our knowledge, this is the first case of a delayed onset of hydrocephalus in a patient with Joubert syndrome.

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.

Metabolic myopathies are heterogeneous hereditary diseases affecting skeletal muscle energy supply. Symptoms usually comprise pain, cramps, hypotonia, weakness, and myoglobinuria.We present a boy with recurrent myalgia and weakness after some minutes of exercise or during febrile infections since early infancy. First laboratory workup at the age of 9 years showed no abnormalities, apart from a slightly elevated creatine kinase. After exclusion of common structural and metabolic myopathies, next generation sequencing panel (4 years after the initial diagnostic metabolic workup) revealed two potentially pathogenic missense mutations in the CPT2 gene (c.149C > A (p.P50H) and c.1459G > A (p.E487K)).Our case underscores the clinical variability of muscle carnitine palmitoyltransferase II (CPT II) deficiency and illustrates a pitfall of diagnostic algorithms for metabolic myopathies. Myalgia following exercise of a few minutes duration would have argued for a carbohydrate and against a fatty acid metabolic defect. However, CPT II deficiency is the most common disorder of muscle fatty acid metabolism and should be considered even in atypical scenarios. Analyses of plasma acyl carnitine profile during acute metabolic crises may help to unmask biochemical markers which are often overlooked in dried-blood analyses.

Introduction Beta-propeller protein-associated neurodegeneration (BPAN) is a very rare, X-linked dominant (XLD) inherited member of the neurodegeneration with brain iron accumulation (NBIA) disease family. Case report We present a female case of BPAN with infantile spasms in the first year, Rett-like symptomatology, focal epilepsy, and loss of motor skills in childhood. Menarche occurred at the age of 9, after precocious pubarche and puberty.Dystonia-parkinsonism as extrapyramidal sign at the age of 10 years resulted in radiological and genetic work-up. Results Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) measured 66/120 points in body part-related dystonia symptoms. Cerebrospinal fluid examination showed dopamine depletion.T2 and B0 sequences of the diffusion-weighted magnetic resonance imaging showed susceptibility artifacts with NBIA-typical hypointense globus pallidus (GP) and substantia nigra (SN). Next-generation sequencing revealed a BPAN-causing pathogenic variant in WDR45 (WD repeat-containing protein 45) gene (c.830 + 1G > A, XLD, heterozygous, de novo). Skewed X-inactivation was measured (2:98). Conclusions Autophagy-related X-linked BPAN disease might still be underdiagnosed in female cases of infantile spasms.Skewed X-inactivation will have mainly influenced the uncommon, very early childhood neurodegenerative symptomatology in the present BPAN case. Oral levodopa substitution led to improvement in sleep disorder, hypersalivation, and swallowing.Reduced white matter and hypointense signals in SN and GP on susceptibility sequences in magnetic resonance imaging are characteristic radiological findings of advanced disease in NBIA. No BPAN-typical halo sign in T1-weighted scan at midbrain level was seen at the age of 11 years. NBIA panel is recommended for early diagnosis.

Background The use of complementary and alternative medicine (CAM) is popular. Parents of children suffering from epilepsy may also consider administering CAM to their children. Systematic data about frequency of and motivations for CAM use, however, are scarce. Methods In a university hospital's neuropaediatric department parents of patients aged 0–18 years suffering from epilepsy were consecutively invited to take part in a structured interview during 4 months in 2014. Results Of the invited parents, 164/165 (99%) agreed to participate. From those, 21/164 (13%) stated that they used CAM in their child. The highest independent predictive value of CAM use was the occurrence of adverse drug events (ADE) of anticonvulsants as judged by parents. Patients affected by ADE had a 5.6 higher chance of receiving CAM compared to patients without ADE. Most commonly used were homeopathy (14/21, 67%) and osteopathy (12/21, 57%). The internet was the most frequently used source of information (14/21, 67%). Of the parents, 10/21 (48%) described positive effects of CAM on seizure frequency, 12/21 (57%) on general condition of their child, and 20/21 (95%) wished to continue CAM for epilepsy therapy. From the non-users of CAM, 91/143 (66%) expressed the desire to learn more about CAM for epilepsy therapy. Limitations Our study was performed in a university hospital in a large urban city in Eastern Germany. CAM user rates can differ in other parts of Germany and Europe, in other institutions and for chronic diseases other than epilepsy. Conclusion The main reason for CAM use was the occurrence of ADE of anticonvulsants. More than half of the parents saw a benefit of CAM for their children. Almost all parents wished to continue CAM use, even those who did not see concrete positive effects.

Epilepsy and bronchial asthma are frequent in adolescents. Data on adolescents' experiences with their disease and on their expectations for the future, however, is scarce. Patients of a university hospital aged 12 to 17 with epilepsy or bronchial asthma were interviewed based on a questionnaire. Forty-five patients with epilepsy and 47 with bronchial asthma were interviewed. Adolescents with epilepsy felt more impaired by their disease (median 2.5; Q25/Q75 0.75/3.0; 6-level Likert scales: 0 = not at all, 5 = very strong) than those with asthma (1.0; 0/3.0; p = 0.017). Seventy-nine patients (85.9%) had never used the Internet to gain information about their disease. Adolescents with epilepsy felt more limited in their career possibilities by their disease (2.0; 0/4.0) than those with asthma (0; 0/2.0; p = 0.001) and had a higher level of concern about passing their disease on to their children (3.0; 0/4.0) than their peers with asthma (1.5; 1.5/3.0; p = 0.016). Girls with epilepsy were more anxious (4.0; 0.5/5.0) than girls with asthma (0; 0/4.0) about complications of the disease regarding pregnancy (p = 0.019).As well adolescents with epilepsy as with asthma described limitations of their daily life and concerns about the future. What is Known: • Epilepsy and bronchial asthma are frequent chronic diseases in adolescents. • Those diseases can affect psychosocial development. What is New: • Adolescents with epilepsy and bronchial asthma described a high burden of their disease, and most adolescents had not used the Internet to inform themselves on their disease. • Especially adolescents with epilepsy fear limitations in their job possibilities, inheritance of their disease and complications in their prospective pregnancy.

Objective We performed a retrospective chart analysis in neonates routinely treated with levetiracetam (LEV) in a university setting. Patients and Methods We assessed clinical characteristics of the included neonates. Documented LEV doses and the duration of treatment were evaluated. To assess LEV effectiveness, we compared the need of any additional anticonvulsant as co- and rescue therapies before and following the initiation of LEV treatment. To assess LEV tolerance, we sought to identify documented adverse drug reactions resulting in a termination of LEV treatment. Results We analyzed a total of 72 neonates receiving LEV with a median gestational age at initiation of LEV treatment of 30 4/7 gestational weeks (min., 24 5/7 /max., 43 0/7 weeks). LEV was applied in target doses of 41.7 mg/kg/d (min., 14.4/max., 106.2 mg/kg/d). Patients received LEV treatment at hospital for a median of 28 days (min., 1/max., 195 days). Additional anticonvulsant therapy decreased a week after LEV treatment was initiated ( p = 0.008). We did not find any cases of terminated LEV treatment resulting from adverse drug reactions. Conclusion Long term use of high LEV doses is rather frequent in immature neonates. Our data indicate good effectiveness and a low risk of adverse drug reactions.

In pediatric patients, brain tumors have been estimated to be the cause for seizures in only 0.2-0.3% of cases, whereas seizures occurred in about 13% of pediatric brain tumor patients at presentation. This survey was conducted to analyze EEG findings in pediatric tumor patients over the past 14 years to evaluate the diagnostic value of preoperative EEG for diagnosis of brain tumors. Surface EEG was obtained in awake patients using the international 10- to 20-electrode placement in all pediatric patients with intracranial neoplasms between 2000 and 2013 at the University Hospital of Leipzig except for those who needed emergency operative treatment. One hundred forty-two pediatric patients with 80 infratentorial and 62 supratentorial tumors (WHO grades I-II: 91 patients; WHO grades III-IV: 46 patients). Symptomatic hydrocephalus was found in 37. Sensitivity and specificity of ophthalmologic examination for predicting hydrocephalus was 0.39 and 0.72. Preoperative EEG has been conducted in 116 patients, showing normal activity in 54 patients (47%). Out of 62 pathologic EEGs, 40 indicated correctly to the site of the lesion, 15 were pathologic despite of infratentorial location of the tumor. Nineteen patients had a history of seizures of which six had normal EEGs. Sensitivity for and specificity of EEG examination for symptomatic epilepsy was 0.68 and 0.7. Conclusion Preoperative routine EEG provides no additional value in the diagnostic algorithm of pediatric train tumors. The low specificity and sensitivity of EEG (even in patients with clinical seizures as primary symptom of a brain tumor) underline that EEG does not contribute to diagnosis and a normal EEG might even delay correct diagnosis.

Menkes disease, an inherited disorder of copper transport, shows a spectrum of different neuroradiological findings. Diffuse brain atrophy, deficient myelination, and subdural hematoma/hygroma were described. Anomalies of the cerebral arteries with elongation and tortuosity are known. We report the neuroradiological follow up of a patient suffering from Menkes disease confirmed by the identification of a deletion of ATP 7A gene. Ultrasound scanning at the age of two months demon- strated normal brain morphology. One month later, magnetic resonance imaging (MRI) showed vermian hypoplasia, brain atro- phy and retarded myelination. Marked widening of cerebral venous sinuses in conventional angiography and in magnetic resonance venography was detected and led to arterial cerebral angiography, which did not disclose an arteriovenous fistula. Despite parenteral copper therapy, on MRI follow up seven months later, extra-axial blood and hygroma were visible and the signs of cerebral atrophy and myelination deficit were more pronounced. In Menkes disease, neuroradiological anomalies can occur early and progress rapidly despite copper therapy. When evaluating magnetic resonance angiography results in neurode- generative diseases, Menkes disease should be suspected not just when cerebral arterial anomalies are demonstrated. Widening of the cerebral venous sinuses might be caused by secondary to brain atrophy or involvement of the vein walls.

ProblemSchool and preschool teachers play a key role in the care of children with epilepsy. Yet, data about their knowledge on epilepsy are scarce.MethodsAssessment of knowledge and attitudes towards epilepsy in teachers by conducting a questionnaire survey in Leipzig and Blankenburg, Germany, from August 2013 to January 2014.Results1243 questionnaires were completed by 302 school teachers, 883 preschool teachers, 56 students and two unclassified participants. Of the respondents, 140 (11%) stated to have already been actively involved in an epilepsy emergency situation, another 148 (12%) as observers. Only 214 (17%) of respondents felt sufficiently prepared for an emergency. A rescue medication had already been applied by 79 (6%) of respondents; only 186 respondents (15%) stated they would be willing to administer a prescribed rescue medication under any circumstances. In response to an open-ended question about the most common fatal outcomes of a seizure, status epilepticus and drowning were rarely mentioned. 233 (19%) of respondents assumed that epileptic seizures cannot result in death. 606 (49%) of respondents were concerned about the legal repercussions to an incorrect response to a seizure.129/403 (32%) of teachers with >20 years of professional experience claimed never to have had a child suffering from epilepsy in their care, even though the prevalence of childhood epilepsy indicates that they should. In total, 1066 (86%) respondents expressed a desire to gain more knowledge on epilepsy.ConclusionsTraining programmes for teachers should be established. Furthermore, a clear legal regulatory framework needs to be set up.

Fetofetal transfusion syndrome is a dreaded cause of morbidity and mortality in monochorionic pregnancies. We present two pairs of twins one of which we have followed for more than 6 years. The donors suffer from cerebral palsy, orofacial, and motor problems, and both are significantly smaller than their recipient twins. Interestingly, cranial MRI revealed medial frontal lobe polymicrogyria, ventriculomegaly, and decreased thickness in both parietal lobes in both donors. We suggest this as a possible feature of fetofetal transfusion syndrome. A minireview of the literature on neuroimaging and neurodevelopmental outcome in fetofetal transfusion syndrome is presented. While the close resemblance of the imaging features of both cases is likely incidental further study of a connection between migration and gyration disorders and fetofetal transfusion syndrome is warranted.

Brain imaging is the most common examination in pediatric magnetic resonance imaging (MRI), often combined with the use of a gadolinium-based contrast medium. The application of gadolinium-based contrast medium poses some risk. There is limited evidence of the benefits of contrast medium in pediatric brain imaging. To assess the diagnostic gain of contrast-enhanced sequences in brain MRI when the unenhanced sequences are normal. We retrospectively assessed 6,683 brain MR examinations using contrast medium in children younger than 16 years in the pediatric radiology department of the University Hospital Leipzig to determine whether contrast-enhanced sequences delivered additional, clinically relevant information to pre-contrast sequences. All examinations were executed using a 1.5-T or a 3-T system. In 8 of 3,003 (95% confidence interval 0.12–0.52%) unenhanced normal brain examinations, a relevant additional finding was detected when contrast medium was administered. Contrast enhancement led to a change in diagnosis in only one of these cases. Children with a normal pre-contrast brain MRI rarely benefit from contrast medium application. Comparing these results to the risks and disadvantages of a routine gadolinium application, there is substantiated numerical evidence for avoiding routine administration of gadolinium in a pre-contrast normal MRI examination.

Background The main source of knowledge on adverse drug events (ADE) are physicians' reports in controlled clinical trials. In contrast, little is known about the parents' perception of ADE of anticonvulsants their children receive. Methods After approval by the local ethics committee, we performed a survey in a neuropediatric outpatient clinic of a university hospital. Based on a structured questionnaire, we interviewed parents of children with current anticonvulsant treatment regarding (i) their fears about potential ADE, (ii) experienced ADE according to parents, and (iii) implications of ADE on the child's life. Results Parents of 150 patients took part in the interview. (i) 95 (63.3%) parents expressed fears concerning ADE, mostly liver injury/liver failure (33 [22%]). (ii) 129 (86%) parents reported experienced ADE, mostly sedation (65 [43.3%]) and abnormal behavior (54 [36%]). (iii) Parents reported substantial implications of ADE on the child's daily life for 84 (56%) children, and 63 (42%) parents expressed a negative impact on the child's development. Conclusion We recognized a great discrepancy between those ADE that were feared and those that were experienced. Parents feared life-threatening ADE and experienced less severe ADE that nevertheless have a negative impact on the child's daily life.

Background: After a first afebrile seizure, EEG in addition to cMRI is recommended for pediatric patients. Once indications requiring immediate treatment are excluded, it is of interest to determine if the results provide a prognostic tool for seizure relapses. Methods: Patients aged between 1 month and 18 years who had a first afebrile seizure between 2006 and 2008 were retrospectively studied and monitored for another 48 months. Results: Out of 248 patients, 62.5% had generalized and 36.3% focal seizures. 34.7% of the EEG results were pathological. 176 patients had a cMRI that showed in 23.3% probable epileptogenic lesions. 3 patients with benign cerebral tumours needed surgical therapy. In the following 48 months 29.4% of the children showed seizure relapses. There was a correlation between epileptic patterns in the EEG and further seizures (p=0.0001). However, the sensitivity of the EEG based diagnoses was 0.6, the specificity 0.78 and the positive predictive value 0.52. There was no correlation between epileptogenic lesions and the probability of seizure relapses. The sensitivity of the cMRI to this effect was 0.36, the specificity 0.74 and the positive predictive value 0.34. Discussion: The EEG is superior to cMRI for predicting seizure relapses. The percentage of noticeable cMRI findings is high but this has low therapeutic relevance and is assumed to largely represent "incidental findings". It is important to question the value of MRI investigations for sedated small children except in the case of emergencies. The key question is whether the cMRI should be deployed to diagnose epilepsy, the probability of seizure recurrences or to classify the entity of a most likely epilepsy.

Aim In Germany, preschool teachers supervise children up to six years of age and are also responsible for supervising older pupils after school. This study explored the impact of a teaching session on epilepsy for teachers in charge of children from 1-10 years of age. Methods We evaluated the benefit of a teaching session offered to all preschool teachers in Leipzig, Germany, in 2014-2015, by asking them to complete the same questionnaire 12-24 months pre-intervention, and 12 months post-intervention. Results Both questionnaires were completed by 123 teachers. The number of teachers who felt they were prepared to handle an acute seizure rose from 36 (29%) pre-intervention to 65 (53%) post-intervention (p

The established standard of pharmacotherapy of the attention deficit hyperactivity disorder is methylphenidate, a drug with very few side effects. A 4-year-old boy with T cell acute lymphoblastic leukemia, and severe damage to the white matter induced by chemo- and radiotherapy was treated with methylphenidate in increasing doses due to marked attention deficit hyper- activity disorder. Liver enzymes, i.e. aspartate aminotransferase, alanine aminotransferase and gamma glutamyltranspeptidase, were slightly elevated prior to therapy. Three weeks into methylphenidate therapy, the patient suffered from recurrent vomiting. Liver enzymes were elevated with alanine aminotransferase at 1260 U/L, aspartate aminotransferase at 499 U/L and gamma glutamyltranspeptidase 284 U/L. Creatine kinase was elevated at 405 U/L, while bilirubin and renal function parameters were within normal levels. Following discontinuation of therapy, liver enzymes returned almost to normal levels within a week. Hepatotoxic reactions to methylphenidate are extremely rare. As methylphenidate inhibits the liver cytochrome P450 system, synergistic toxic effects are possible in theory. An elevated creatine kinase level would be possible within the framework of autoimmune reactions. Patients with increased risk (i.e. age below 6 years, hepatic stress due to prior pharmacotherapy) should be treated with methylphenidate, only under close clinical and laboratory monitoring.

BACKGROUND: Anticonvulsants require special consideration particularly at the interface from hospital to ambulatory care. PATIENTS AND METHOD: Observational study for 6 months with prospectively enrolled consecutive patients in a neuropediatric ward of a university hospital (age 0

Hydrocephalus is still a not well-understood diagnostic and a therapeutic dilemma because of the lack of sufficient and comprehensive model of cerebrospinal fluid circulation and pathological alterations. Based on current studies, reviews, and knowledge of cerebrospinal fluid dynamics, brain water dynamics, intracranial pressure, and cerebral perfusion physiology, a new concept is deducted that can describe normal and pathological changes of cerebrospinal fluid circulation and pathophysiology of idiopathic intracranial hypertension.

A case of an 8-year-old-boy with shunt-dependent occlusive hydrocephalus after resection of a cerebellar medulloblastoma is presented, who experienced repeated episodes of severe neurologic deterioration with signs and symptoms of raised intracranial pressure after spinal tapping. However, intracranial pressure was recorded within low ranges, only up to the opening pressure of the implanted adjustable shunt valve. Multiple shunt revisions were performed, until the condition was recognized as acute normal pressure hydrocephalus. Either enforced recumbency and downadjustment of the valve system to 0 cm H(2)O alone or external ventricular drainage seems to be successful to resolve the critical condition, depending on severity of the symptoms. The case illustrates that acute pathologic enlargement of the ventricular system is not always associated with increased intracranial pressure, even when typical signs and symptoms are present. The very rare entity of acute normal pressure hydrocephalus by two separated compartments is postulated based on the pulsatile vector force theory of brain water circulation.

Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of tumor resection, the application in children remains an off-label use. Even though most pediatric study protocols require a complete resection for improving outcome parameters, only few pediatric patients have been operated with fluorescence guidance, and it remains questionable, whether and which pediatric tumors show useful fluorescence. We present casuistic reports of application of 5-ALA in children collected from three different neurosurgical departments. In children with suspected malignant intracerebral tumor or recurrence, individual informed consent was obtained in each case from the parents. 5-ALA was administered according to the adult protocol, with 20 mg/kg, 2 h before induction of anesthesia. We retrospectively analyzed 18 patients (13 male, 5 female; age 3–18 years), using the intraoperative neurosurgical protocol, the postoperative MRI results, and the follow-up clinical examinations. The use of 5-ALA fluorescence guidance proved to be safe in our group of pediatric patients. Fluorescence guidance was most useful for recurrent glioblastoma resection. Medulloblastoma tissue displayed fluorescence only inconsistently, and most pilocytic astrocytoma remained without staining. Ganglioglioma showed partial staining in the central tumor areas, without allowing the use for circumferent resection. The off-label use of 5-ALA fluorescence guidance in pediatric patients appears to be most useful in recurrent high-grade gliomas. Fluorescence accumulation in other pediatric brain tumor entities is not predictable and should be evaluated in future clinical studies before being integrated into the current treatment protocols.

Spinal intradural arachnoid cysts are rare with only a few patients reported so far. Idiopathic, traumatic, posthemorrhagic, and postinflammatory causes have been reported in the literature. Especially, idiopathic lesions, in which other possible etiological factors have been ruled out, seem to be rare. We systematically reviewed the literature in regards to localization within the spinal canal, treatment options, complications, and outcome. Additionally, we present management strategies in two progressively symptomatic children less than 3 years of age with idiopathic intradural arachnoid cysts. In total, 21 pediatric cases including the presented cases have been analyzed. Anterior idiopathic spinal arachnoid cysts are predominantly located in the cervical spine in 87.5 % of all cases, whereas posterior cysts can be found at thoracic and thoracolumbar segments in 84.6 % of the patients. Most children presented with motor deficits (76.2 %). Twenty-five percent of anterior spinal arachnoid cysts caused back pain as the only presenting symptom. Open fenestration by a dorsal approach has been used in the vast majority of cases. No major surgical complications have been reported. Ninety-four percent of all patients did improve or showed no neurological deficits. Recurrence rate after successful surgical treatment was low (9.5 %). Idiopathic spinal intradural arachnoid cysts can present with neurological deficits in children. Pathologies are predominantly located in the cervical spine anteriorly and in thoracic and thoracolumbar segments posteriorly to the spinal cord. In symptomatic cases, microsurgical excision and cyst wall fenestration via laminotomy are recommended. Our radiological, intraoperative, and pathological findings support the cerebrospinal fluid obstruction and vent mechanism theory of arachnoid cysts.

Quality of parents' performance in administering anticonvulsive rescue medication to their children suffering from seizures is unknown. After obtaining ethical approval, we used a questionnaire to ask parents of children with seizures, who had been prescribed rescue medications, about their experience in administering those. To assess the frequency of actually committed drug-handling errors, we let them administer rescue medications to dummy dolls. An expert panel rated the clinical risk of handling errors from "1" (lowest) to "6" (highest). Eighty-one parents completed the study. In the questionnaire, 85 % (100 %) of parents that already conducted rectal (buccal) administration reported that they had never experienced problems. The number of rectal administrations with at least one handling error (97 %, 58/60) was higher than in buccal administration (58 %; 14/24; p 0.001). According to logistic regressions, previous use of rescue medication was not a predictor of the number of committed errors per process (n. s.). All errors were rated with a high clinical risk (class 4-6).By observing parents' administration of rescue medication to dummy dolls, we found a high frequency of clinically relevant drug-handling errors. Most parents, however, self-reported to have never experienced problems while administering rescue medications to their children.• For seizures with duration of more than 5 min, the administration of anticonvulsive rescue medication is recommended. • Outside the hospital, the administration of rescue medication to children is performed most frequently by their parents. What is New: • Most of the parents reported that they had never experienced problems in handling anticonvulsive rescue medication. • But in the observed drug-handling performances, identified errors committed by parents were alarmingly frequent and pose a high clinical risk according to an expert panel.

The role of prolonged febrile seizures in the genesis of hippocampal sclerosis is controversial; statistical analysis and data from epilepsy surgery suggest a causal relationship. A three-year-old boy had an initial febrile seizure with a transient postictal flaccid hemiparesis. Magnetic resonance imaging (MRI) showed no abnormality of the hippocampal areas of both sides. At the age of four a prolonged febrile seizure occurred. An MRI was done immediately and gave abnormal results in the right hippocampal area where T2-weighted and dark fluid sequences showed increased signal intensity; in diffusion-weighted sequences this region appeared hyperintense, which is in agreement with acute neuronal damage. Six weeks later the right hippocampal region still gave hyperintense signals in MRI (T2-weighted), while the diffusion coefficient was unremarkable. A final MRI scan was done 16 months following the second febrile seizure where the right hippocampal region still gave hyperintense signals and was reduced in size as is typical for hippocampal sclerosis. This case illustrates the development of a hippocampal lesion following a prolonged focal febrile seizure without any preexisting hippocampal lesion or positive family history. This suggests that prolonged febrile seizures alone can be a causative factor of hippocampal sclerosis.

Neurofibromatosis type 1 is the most common of the phakomatoses and the clinical follow-up is an interdisciplinary challenge. The data of 27 patients with NF1 were systematically reviewed and compared to data from the literature. All of our patients had clinical signs of NF1. Besides the classic criteria cafe-au-lait spots (100%), freckling (48,1%), positive family history (44,1%), neurofibromas (40,7%), Lisch nodules (22,2%) and optic pathway tumors (22,2%) there were developmental delay (40,7%), macrocephaly (33,3%), strabism (29,6%), scoliosis (18,5%), epilepsy (14,8%), pubertal anomalies (14,8%), short stature (11,1%) and tics. Morphologically, CNS hamartomas (55,5%), astrocytomas (22,2%) and one pheochromocytoma became apparent. Special findings consist of one aneurysm of internal carotic arteria, juvenile xanthogranulomas, a case of pulmonary stenosis and an intracardial tumor. Four new mutations in the NF1 gene were found. Regular screening of optic glioma with MRI had no clinical significance. In contrast to other authors, one of our patients with optic glioma showed clinical progress after twelve years of age. The detection of astrocytomas led only to therapeutic consequences, when clinical signs or symptoms occurred. As with other authors, we found no potential for CNS hamartoma to proliferate. In three cases with pubertal anomalies we found CNS gliomas, which indicates the need for MRI. The expense of screening, apart from clinical surveillance, seems inadequate in relation to clinical relevance and costs. We describe four new mutations in the NF1 gene; there have been no specific genotype-phenotype correlations. Neurofibromatosis type 1 and associated clinical abnormalities in 27 children.

We describe here the spontaneous remission of a diffuse brainstem lesion found in an infant at the age of 7 weeks. Clinical and MRI characteristics strongly suggested a diffuse pontine glioma. Repeated MRI studies showed a continuous decrease in the size of the lesion, which was no longer visible by the age of 27 months. Spontaneous remission of diffuse pontine glioma is extremely rare; to our knowledge there are reports of only three similar cases.

Treatment of aqueductal stenosis (AQS) has undergone several paradigm shifts during the past decades. Currently, endoscopic ventriculostomy (ETV) is recommended as treatment of choice. Several authors have addressed the issue of variable ETV success rates depending on age and pathogenetic factors. However, success rates have usually been defined as "ETV non-failure." The aim of the study was a retrospective analysis of radiological and neurological treatment response after ETV or VP-shunting (VPS) in age-dependent subtypes of AQS.Eighty patients (median age 12.0 years, range 0-79 years) have been treated for MRI-proven aqueductal stenosis. Neurological treatment success was defined by neurological improvement and, in childhood, head circumference. Radiological response was measured as Evan's index in follow-up MRI. Initial signs and symptoms, type of surgery, and complications were analyzed.Four types of AQS have been defined with distinct age ranges and symptomatology: congenital type I (n = 24), chronic progressive (tectal tumor-like) type II (n = 23), acute type III (n = 10), and adult chronic (normal-pressure hydrocephalus-like) type IV (n = 23). Retrospective analysis of neurological and radiological outcome suggested that congenital type I (1 years of age) may be more successfully treated with VPS than with ETV (81 vs. 50 %). Treatment of chronic juvenile type II (age 2-15) by ETV 19 % compared to 57 % after VP-shunt, but similar neurological improvement (80 %). There has been no influence of persistent ventriculomegaly in type II after ETV in contrast to VPS therapy for neurological outcome. Adult acute type III (age15 years) responded excellent to ETV. Chronic type IV (iNPH-like) patients (age21) responded neurologically in 70 % after ETV and VPS, but radiological response was low (5 %).AQS can be divided into four distinct age groups and types in regards of clinical course and symptomatology. Depending on the AQS type, ETV cannot be unequivocally recommended. Congenital type I AQS may have a better neurological outcome with VP-shunt whereas acute type III offers excellent ETV results. Chronic progressive type II still requires prospective investigation of long-term ETV outcome, especially when ventriculomegaly persists. Late chronic type IV seems to result in similar outcome after VP-shunt and ETV.

BACKGROUND: About 25 % of children in the first three years attract attention due to regulatory disorders like un-apeasable crying, chronic fussing, sleep- and feeding-disorders as well as excessive temper-tantrums. Meanwhile there are many counselling services in Germany, which provide help for parents. PATIENTS: Data of 153 families with infants and toddlers till the age of three, who visited the Leipzig counselling service during a period of two years. METHOD: Paediatric-neurodevelopmental status and extensive psychosocial anamnesis following a semi-structured interview-guideline. RESULTS: 74 % of the families attended one or two times, in 60 % of these cases an improvement or solution of the problem occurred. 18 % of the mothers showed depressive symptoms, which are linked to the absence of the partners on a highly significant level. 23 % of the families were acutely psycho-socially stressed; these families were neither able to use the offered interventions in an appropriate way, nor were others able to use it at all. CONCLUSIONS: The surveyed data support the assumption, that early childhood intervention provides help briefly and economically. For the relatively large group of "multi-problem families" in the sample we can not yet offer intervention strategies, which could help these children to reduce their high developmental risk.

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 is rare.Sixty-nine patients were examined after congenital hydrocephalus had been treated between 1971 and 1987 at the Department of Pediatric Surgery (University of Leipzig) within the first 12 months of life. Median age of patients was 32 years (range 25-42 years). Patients agreed to undergo a contemporary hydrocephalus assessment.Seven patients (10.1%) became shunt-independent before adulthood. By the age of 20, 82% of the patients had needed at least one shunt revision, 100% by the age of 30. 21.7% of the primary valves (Spitz-Holter) remained intact without revision until today up to 35 years (mean functional intactness 23 years). Shunt infections occurred in 4.3% of primary implantations. 48% of the patients had a good functional outcome (mRS = 0-1). 40.9% of the patients attended regular school. In summary, 75% patients work on a daily basis. 44.6% live an independent life, 35.4% rely on parental supervision, and 20% depend on professional care institutions.Compared to the pre-shunt era, surgery within the first year of life is advantageous regarding visual function, educational progress, and social results. The outcome achieved throughout childhood remains stable during adult life as long as catastrophic events of shunt malfunction can be prevented. Epilepsy, motor deficits, acute shunt dysfunction, and problems of social integration as well as aging parental caregivers seem to be prominent factors of morbidity in adulthood.

In contrast to the recommendations of the International Liga against Epilepsy, many hospitals perform routinely complete ophthalmological examinations in children admitted after a first seizure. As there is no study available to date to prove the benefit of complete eye examinations in first seizure diagnosis, we conducted a study to analyse the value of a complete ophthalmological examination. All children aged 1 month to 18 years who were admitted to the children's university hospital of Leipzig with the clinical diagnosis of a first convulsive or non-convulsive afebrile seizure between 1999 and August 2005 were investigated. All children who had obtained a complete ophthalmological examination within 72 h after the seizure were included in the observational study. A total of 310 children were analysed in the study. Two hundred thirty patients had a tonic-clonic afebrile seizure, the others focal, complex-partial seizures or absences. Two hundred seven out of 310 children showed no ophthalmological pathologies. Eighty-three children had refraction anomalies or strabism, 18 children had optic atrophy, three had congenital eye muscle paresis, and three had malformations. A 16-year-old girl had a homonymous quadrantanopia due to an occipital glioglioma that caused the seizure. An 11-year-old girl had a retinal haemorrhage without any brain lesions after a fall caused by a first tonic-clonic seizure. None of the ophthalmological findings influenced directly the immediate clinical course of diagnosis and treatment of the seizure. Our data suggest that routine ophthalmological examination in all children does not have additional benefit in the first seizure diagnosis management.

BACKGROUND: Clarifying the cause of global developmental and speech delay is of considerable significance in pediatrics. We present the clinical phenotype of the 22q13 deletion syndrome - also known as Phelan-McDermid syndrome - and show the diagnostic options. PATIENT: We report on a female patient with muscular hypotonia, tall stature, minor facial dysmorphism, retarded motor and mental development, and severe speech delay. METHOD: Chromosomal analysis was performed first on peripheral lymphocytes on GTG-banded chromosomes. Fluorescence in situ hybridization (FISH) analysis was carried out using the dual-color LSI DiGeorge/VCFS Region Probe (TUPLE1, N25) (Vysis/Abbott) and the subtelomeric probe tel 22q13.3 (Tel Vysion 22q). RESULTS: The analysis of metaphase chromosomes at 450 band resolution showed a normal female karyotype 46,XX. FISH analysis revealed a 22q13 deletion. CONCLUSION: Muscular hypotonia and developmental delay are non-specific findings observed in many genetic syndromes. In association with severe speech delay and normal or advanced growth pediatricians should consider 22q13 deletion syndrome as a potential cause and initiate a genetic examination.

Since anticonvulsants such as valproate or oxcarbazepine have quite a disadvantageous profile of possible adverse drug events (ADEs), safer alternatives are being sought. The newer anticonvulsant levetiracetam is often considered advantageous. We performed a chart review of children and adolescents aged from 0.5 to 16.9 years, who had been started on an initial monotherapy with levetiracetam, valproate, or oxcarbazepine between 2007 and 2011, in order to analyze the therapy’s failure rate during the first year. We differentiated failure of monotherapy due to a lack of effectiveness and due to ADEs. No psychometric tests were performed. Lack of effectiveness and inacceptable ADEs were assumed according to the judgment of physicians and families. Anticonvulsive monotherapy failed in 29/61 (48 %) levetiracetam patients and in 18/49 (37 %) valproate patients (for focal and generalized epilepsies; n.s.). This was caused by a lack of effectiveness in 25/61 (41 %) levetiracetam patients and in 11/49 (22 %) valproate patients (p ≤ 0.05). A modification of therapy due to ADEs was performed in 4/61 (7 %) levetiracetam patients and in 7/49 (14 %) valproate patients (n.s.). An anticonvulsive monotherapy failed in 21/42 (50 %) patients treated with levetiracetam and in 10/34 (29 %) patients treated with oxcarbazepine (for focal epilepsies; n.s.). Changes of monotherapy were caused by a lack of effectiveness in 17/42 (40 %) of levetiracetam patients and in 6/34 (18 %) of oxcarbazepine patients (p ≤ 0.05). ADEs leading to changes in therapy were reported for 4/42 (10 %) of levetiracetam and 4/34 (12 %) of oxcarbazepine patients (n.s.). An initial monotherapy of levetiracetam failed more frequently due to a lack of effectiveness than a monotherapy with valproate or oxcarbazepine. We found no significant difference in therapy failure due to ADEs.

Background Impaired glucose tolerance and type 2 diabetes are well-known features in patients with Turner syndrome. To the best of our knowledge, there is only one reported case of hyperinsulinemic hypoglycemia associated with a complex mosaic Turner syndrome available in the current literature. Patient We report on the case of a 13-month-old girl with a complex mosaic Turner genotype and mild hyperinsulinemic hypoglycemia responsive to diazoxide therapy. Results Cytogenetic analyses showed two or possibly three cell lines. Sixty percent of the cell lines had a 45,X genotype and the rest had 46,XX with a marker ring chromosome. Diagnosis of a mosaic Turner syndrome and mild Kabuki-like phenotype was confirmed. Conclusions Despite the rareness of this case, clinicians should be aware of the possibility of hyperinsulinemic hypoglycemia in patients with Turner syndrome to prevent further brain damage caused by hypoglycemic episodes and seizures. Although the mechanism leading to hyperinsulinism in this condition is still unknown, the present report discusses this rare presentation and gives an overview on the current literature regarding this case.

TSC is a multisystem genetic disorder predisposing to multiple organ manifestations and developmental problems. Clinical follow-up of patients remains a challenge for the caring paediatrician. Methods: We performed a retrospective analysis of clinical manifestations, diagnostic and therapeutic data in 20 children with the diagnosis of tuberous sclerosis complex (TSC) to answer the following questions: are the clinical guidelines and imaging strategies appropriate to discover complications, are there significant early predictors of long-term prognosis, what is the age range for signs and symptoms to occur. Results: Cardiac rhabdomyoma were present in 18 children and occurred as earliest manifestation. 8 of these exhibited associated arrhythmia or congenital cardiac anomalies. Seizures combined with cortical tubers and subependymal nodules occurred in 18 patients and were most likely to start in infancy, which was associated with later cognitive impairment. Cutaneous manifestations (15 children) occurred in late childhood and school age, whilst renal angiomyolipomas (11) developed in puberty. Discussion: The clinical course and imaging strategies are compared with data from previous studies. A review of TSC in regard to the multiple manifestations is provided.

We report a 1-year-old child with the prenatal (week 29 + 5) diagnosis of a brain tumor. The parents were informed about all aspects of prognosis and options concerning termination of pregnancy. The parents opted for an aggressive therapeutic approach after extensive and informative case conferences and counseling. The histopathological diagnosis after partial tumor resection was choroid plexus carcinoma, two weeks thereafter tumor size was progressive. The parents opted for palliative treatment at this stage. The patient died at the age of one year. Ethical aspects have to be actively considered and addressed when caring for children with choroid plexus carcinoma.