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Psychogenic gait disorders in children and adolescents represent a unique neuropediatric and rehabilitative challenge. The inability to walk frequently strikes abruptly. Triggers are not easily identifiable. Patients are commonly admitted to the hospital in an emergency. In view of the dramatic clinical picture, parents are perturbed. They expect rapid diagnostic clarification and therapy. If physical, laboratory, and X-ray examinations do not disclose any significant pathological findings, parents generally insist on consulting diverse specialists and clinics. The pivotal point of the course of treatment is the parent–doctor–patient relationship. This is notably true when child psychologists or psychiatrists have to be consulted. Typical risks and decision conflicts of the rehabilitation dynamics are described – these are augmented by several case vignettes.

Cystic fibrosis (CF) is a rare genetic multisystemic disorder with progressive abdominal and pulmonary involvement. Pain is still an underestimated symptom in CF patients.A comprehensive review of guidelines and scientific literature on the topic was performed and combined with findings from pain management in a young CF patient with progressive thoracic pain.German CF guidelines do not cover diagnosis and management of pain in these patients. Studies from Europe and the United States report interactions between intensity of pain and mortality in CF, but do not include data on the efficacy of pain management. These data and clinical observations of a CF patient with episodes of intense thoracic pain are used to illustrate the specific challenges in pain relief.Pain management in CF requires meticulous monitoring as well as an interdisciplinary approach and should be implemented in the German CF guidelines. The authors also want to suggest recommendations for the treatment of thoracic pain in CF. The range and severity of organ involvement complicates the use both of opioids and non-opioids. Especially opioid treatment carries the risk of hypoxia and opioid-induced constipation (OIC) and needs close medical supervision.HINTERGRUND: Die zystische Fibrose (CF) ist eine multisystemische progrediente Stoffwechselerkrankung mit vorwiegend abdomineller und pulmonaler Beteiligung. Schmerzen sind für Betroffene ein weiteres komplexes und von den Behandlern unterschätztes Problem.Eine Literaturrecherche deutschsprachiger Leitlinien und englischsprachiger Studien zum Thema CF und Schmerzen wurde durchgeführt, zusätzlich die Beobachtungen zur Diagnostik und Therapie eines CF-Patienten mit progredienten thorakalen Schmerzen ausgewertet.Die Recherche ergab, dass zur Diagnostik und Therapie thorakaler Schmerzen bei CF keine deutschsprachigen Leitlinien oder Konsenspapiere existieren. Die europäischen und amerikanischen Erhebungen zeigen aber die große Relevanz des Themas und postulieren einen Zusammenhang von Schmerzintensität mit einer erhöhten Mortalität. Sie enthalten jedoch keine Daten zur Effektivität der Schmerztherapie. Anhand dieser Daten und des Fallberichts eines jungen CF-Patienten mit stärksten Thoraxschmerzen bei pulmonalen Exazerbationen lassen sich die CF-spezifischen Herausforderungen der Schmerztherapie illustrieren. Neben den Schmerzen an sich sind auch Analgetika angesichts der multiplen Organdysfunktionen mit besonderen Risiken wie gastrointestinalen Blutungen, opioidinduzierter Atemdepression oder opioidinduzierter Obstipation verbunden.Schmerztherapie bei Patienten mit zystischer Fibrose und Multiorganbeteiligung erfordert ein sorgfältiges Monitoring und interdisziplinäres Handeln. Empfehlungen zum Schmerzmanagement sollten in die deutschsprachigen CF-Leitlinien aufgenommen werden.

Noch langst nicht alle neurometabolischen Erkrankungen sind heute behandelbar. Aber in den letzten Jahren hat sich die therapeutische Landschaft radikal verandert. Heute stehen fur viele Krankheiten Therapieoptionen zur Verfugung. Mit den kunftigen Moglichkeiten der Gentherapie sehen wir weiterem therapeutischen Fortschritt entgegen.

Cystic fibrosis (CF, OMIM 219700) is a rare genetic disorder caused by a chloride channel defect, resulting in lung disease, pancreas insufficiency and liver impairment. Altered L-arginine (Arg)/nitric oxide (NO) metabolism has been observed in CF patients&rsquo, lungs and in connection with malnutrition. The aim of the present study was to investigate markers of the Arg/NO pathway in the plasma and urine of CF patients and to identify possible risk factors, especially associated with malnutrition. We measured the major NO metabolites nitrite and nitrate, Arg, a semi-essential amino acid and NO precursor, the NO synthesis inhibitor asymmetric dimethylarginine (ADMA) and its major urinary metabolite dimethylamine (DMA) in plasma and urine samples of 70 pediatric CF patients and 78 age-matched healthy controls. Biomarkers were determined by gas chromatography&ndash, mass spectrometry and high-performance liquid chromatography. We observed higher plasma Arg (90.3 vs. 75.6 &micro, M, p &lt, 0.0001), ADMA (0.62 vs. 0.57 &micro, M, p = 0.03), Arg/ADMA ratio (148 vs. 135, p = 0.01), nitrite (2.07 vs. 1.95 &micro, M, p = 0.03) and nitrate (43.3 vs. 33.1 &micro, 0.001) concentrations, as well as higher urinary DMA (57.9 vs. 40.7 &micro, M/mM creatinine, p &lt, 0.001) and nitrate (159 vs. 115 &micro, M/mM creatinine, p = 0.001) excretion rates in the CF patients compared to healthy controls. CF patients with pancreatic sufficiency showed plasma concentrations of the biomarkers comparable to those of healthy controls. Malnourished CF patients had lower Arg/ADMA ratios (p = 0.02), indicating a higher NO synthesis capacity in sufficiently nourished CF patients. We conclude that NO production, protein-arginine dimethylation, and ADMA metabolism is increased in pediatric CF patients. Pancreas and liver function influence Arg/NO metabolism. Good nutritional status is associated with higher NO synthesis capacity and lower protein-arginine dimethylation.

OBJECTIVES: The objective of this study was to use the recommended total daily food amounts of the German ‘Dietary Scheme for the first year of life’ (for the first time) to calculate the potential exposure of substances in the infant diet from a public health perspective. Erucic acid was taken as a concrete example, because the European Food Safety Agency (EFSA) recently issued a Tolerable Daily Intake (TDI) for erucic acid with a special note that vulnerable groups, especially young children, may be particularly at risk of exceeding the TDI. METHODS: The age of about 1 month with the highest consumption per kg body weight was chosen for scenarios for the phase of exclusive milk feeding, the age of about 8 months for the CF phase. Principle of calculation was: erucic acid exposure = food consumption volume per kg bodyweight per day x erucic acid concentration in food (from European studies for breastmilk, EFSA food samples for formula, current German market analysis for rapeseed oil, EU food law). We calculated 6 scenarios for the milk phase (4 formula-feeding, 2 breastfeeding) and 8 scenarios for the CF phase (5 CF + formula-feeding, 3 CF + breastfeeding). RESULTS: Out of the 14 scenarios, only 3 resulted in exposures in the safe range below the TDI (range 4.4.– 6.0 mg/kg BW). All scenarios assuming either high consumption (p95) or high concentration led to high exceedances of the TDI (range 7.5–26.2 mg/kg BW), especially when using maximum values of EU law for formula or vegetable oils (33.6 and 43.2 mg/kg BW respectively). CONCLUSIONS: The Dietary Scheme proved to be a suitable frame to calculate the potential exposure of substances in foods forming the daily infant diet. The results give cause for concern, as the calculated high exposure to erucic acid in the scenarios occurs during infancy as a particularly sensitive developmental period and results from the food-based recommendations as public health guidelines. Considering the scarcity of data, in addition to the proven low erucic acid concentrations in rapeseed oil in Germany, it is imperative to analyze the erucic acid content of mature breast milk and formula as well. FUNDING SOURCES: Union for the Promotion of Oil and Protein Plants (UFOP, Berlin, Germany).

Benign Rolandic Epilepsy (BRE) is one of the most common epilepsy syndromes in childhood. Although global intellectual performance is typically normal in BRE-patients, problems were found in specific cognitive domains. To summarize recent empirical findings concerning cognitive development in children with BRE a systematic literature search of clinical studies published between 2009 and 2015 was performed. 19 studies of relevance were found.In most recent studies children with BRE consistently showed general intellectual performance within the normal range. However, in two of the studies patients showed a significantly poorer (but still normal) performance in comparison to controls. The studies provide clear indications for a high prevalence of impairments in language (10 out of 12 studies) and academic performance (6 out of 8 studies) in children with BRE. Regarding deficits in other cognitive domains (attention, memory, visual/auditory perception, executive functions) current findings are inconsistent. In addition, no clear results are found in studies examining cognitive development after remission of BRE. Studies on the relationship between selected clinical/electroencephalographic characteristics (e. g. EEG-patterns, focus lateralization) and cognitive performance and studies on potential benefits of anti-epileptic therapy for cognitive functions also have not yielded consistent results. Studies using fMRI and evoked potentials provide evidence for functional reorganization of neural networks in BRE.Due to the developmental risks in children with BRE early cognitive assessment, early treatment and follow-up assessments are important.

Background: Very low-birth-weight infants with birth weight less than 1,500 g have an increased risk for a worse neurocognitive outcome. Early therapeutic intervention can reduce the level of developmental disorder. To detect the infants with the need of early support it is important to define risk factors affecting the development beside birth weight. Method: During the years 2009 to 2013, a total of 209 very low-birth-weight infants were treated in our neonatal intensive care unit level 1, of which 187 survived. With standardized questionnaire the maternal graduation was asked. At the corrected age of 24 months, we performed a follow-up examination with the Bayley Scales of Infant Development II to the families. The collected data were analyzed with Excel and the statistical program GraphPad Prism (version 4.0). Results: Eleven percent of the parents gave no information about the maternal graduation, 9% of the mothers did not have any school degree, 16% had a certificate of lower German secondary education, 25% had a certificate of middle secondary education, 8% had higher German secondary education, and 31% had a final German secondary-school examination. One hundred fifty (80%) of the surviving infants had participated the follow-up examination. Both participation of the follow-up examination and MDI (mental developmental index) were depending on the maternal graduation. Conclusion: Very low-birth-weight infants of women with low socioeconomic status rarely take part in follow-up examinations and have a worse neurocognitive outcome. In our region (Ruhrgebiet) the part of mothers without or with low school graduation is higher than in other regions of Germany. It is important to register the maternal graduation to detect families with the need of follow-up examinations and early interventions.

Introduction: Mutations in the KCNQ2 gene lead to autosomal dominant benign neonatal seizures or early-onset epileptic encephalopathy. We describe here a female patient with focal epileptic seizures starting from four months of age, carrying a heterozygous duplication of exons 9 – 17 of the KCNQ2 gene. Case Presentation: It is the second child of German non-consanguineous parents without any family history for seizures or epilepsy. After uneventful pregnancy, delivery and neonatal period, the patient developed focal seizures with impairment of awareness several times per week. Cranial MRI, screening for inborn disorders of metabolism or prenatal infections (TORCH) did not show pathogenic results. A panel analysis for epileptic encephalopathies (CeGaT) revealed a heterozygous duplication of exons 9 to 17 of the KCNQ2 gene which was classified as variant of unknown significance. With application of Levetiraetam (at least 40 mg/kg daily, blood level of ~10 μg/mL) absence of seizures except for febrile situations was achieved. After the 7th month, no more seizures were observed, even during infections, and Levetiraetam therapy could be gradually reduced and finally stopped. Psychomotor development of the patient is almost normal. Due to muscular hypotonia, she received physiotherapy, but the developmental milestones were all reached age-appropriately. Conclusion: The clinical interpretation of variants of unknown significance revealed through a panel analysis is often difficult, even with incorporation of data from large databases. So far, a partial KCNQ2 duplication, of exons 3 to 12, has been described only once in the literature in a patient with benign neonatal epilepsy. The reported disease course in our patient carrying another partial duplication of KCNQ2 suggests a benign outcome in this family as well.

Errors in fluid management can lead to significant morbidity in children. We conducted an experimental animal study to determine the margin of safety in accidental hyperinfusion of different glucose and electrolyte containing solutions.Fifteen piglets [bodyweight 12.1 (sd 2.0) kg] were randomly assigned to receive either 100 ml kg⁻¹ of balanced electrolyte solution with glucose 1% (BS-G1), hypotonic electrolyte solution with glucose 5% (HE-G5), or glucose 40% solution (G40) over 1 h. Blood electrolytes, glucose, and osmolality and intracranial pressure (ICP) were measured before, during, and after fluid administration.Hyperinfusion of BS-G1 led to moderate hyperglycaemia [baseline 3.4 (sd 1.3) mmol litre⁻¹, study end 12.6 (1.8) mmol litre⁻¹], but no other relevant pathophysiological alterations. Hyperinfusion of HE-G5 produced marked hyperglycaemia [baseline 3.9 (1.2) mmol litre⁻¹, study end 48.6 (4.3) mmol litre⁻¹, P0.05] and hyponatraemia [baseline 136.4 (1.3) mmol litre(-1), study end 119.6 (2.1) mmol litre⁻¹, P0.05], whereas osmolality remained stable during the course of the study. Hyperinfusion of G40 induced acute hyperglycaemic/hyperosmolar decompensation with an extreme decrease in serum electrolytes [e.g. sodium baseline 138 (1.1) mmol litre⁻¹, 30 min 87.8 (6.4) mmol litre⁻¹, P0.01], leading to cardiac arrest after infusion of 50-75 ml kg⁻¹. ICP remained within a physiological range in all groups.In an animal model of accidental hyperinfusion, BS-G1 showed the widest margin of safety and can therefore be expected to enhance patient safety in perioperative fluid management in children; HE-G5 proved significantly less safe; and G40 was found to be outright hazardous.

In 1991, Biedermann coined the term "kinetic imbalance due to suboccipital strain" ("KiSS-syndrome"). He assumed a functional abnormality of the suboccipital-high cervical spine, resulting in positional preference of the infant;s head. A broad spectrum of symptoms and complaints have been attributed to "KiSS-Syndrome". Patients are advised to undergo manual therapy, with pressure applied locally in order to readjust the cervical spine. Life threatening side-effects have been published repeatedly. We present two infants with brain tumours who developed torticollis and further neurological findings such as ataxia and reflex differences. In both cases, symptoms caused by the tumour were interpreted as "KiSS-syndrome", and appropriate diagnostics and therapy were delayed for months. There is no scientific evidence for the actual existence of "KiSS-syndrome" as a clinical entity or for the positive effects of manual therapy. Approximately 12% of all infants

SIOD is a multisystem disorder caused by a mutant chromatin remodelling protein. The main clinical findings are spondyloepiphyseal dysplasia with disproportionate growth restriction, defective cellular immunity, and steroid-resistant nephrotic syndrome secondary to biopsy proven FSGS leading to ESRF. Concerning ESRF, kidney transplantation is the therapy of choice since FSGS does not recur in the graft. However, with respect to the underlying immune disorder and the increased susceptibility to life threatening infections, the question of the optimal immunosuppressive therapy after renal transplantation remains unresolved. Under conventional immunosuppressive regimens some SIOD patients have developed severe disseminated cutaneous papilloma virus infections or EBV associated lymphoproliferative disease. We present several cases of children with SIOD (four of five had SMARCAL1 mutations) and monotherapy maintenance immunosuppression after renal transplantation and compare them with 13 patients from the SIOD registry. We have found that post-renal transplantation immunosuppressive monotherapy results in a good outcome with a reduced number of severe infections. Due to the underlying immunodeficiency in SIOD, limited immunosuppression may be possible without increasing the risk of acute or chronic rejection.

Item does not contain fulltext Barth syndrome is known as a highly recognizable X-linked disorder typically presenting with the three hallmarks: (left ventricular non-compaction) cardiomyopathy, neutropenia, and 3-methylglutaconic aciduria. Furthermore, growth retardation, mild skeletal myopathy, and specific facial features as well as mitochondrial dysfunction in muscle are frequently seen. Underlying mutations are found in TAZ and lead to defective cardiolipin remodeling.Here, we report atypical clinical manifestations of TAZ mutations in two male patients initially presenting with growth retardation and very mild skeletal myopathy. As other phenotypic hallmarks were missing, Barth syndrome had not been suspected in these patients. One of them has been incidentally diagnosed in the frame of an in-depth cardiolipin research analysis, while the underlying genetic defect was unexpectedly identified in the second one by exome sequencing. CONCLUSION: These cases underline that TAZ mutations might well be an underdiagnosed cause of skeletal myopathy and growth retardation and do not necessarily manifest with the full clinical picture of Barth syndrome.

Das Hurler-Syndrom (MPS 1H) ist eine progressive, autosomal-rezessiv vererbte Erkrankung der Mukopolysaccharide, die zu verminderter Lebensqualitat und vorzeitigem Tod fuhrt. Die prasentierten beiden Kasuistiken belegen den gunstigen Verlauf der psychomotorischen Entwicklung bei Kindern mit MPS 1H nach Blutstammzelltransplantation (BSCT). Die intrakranialen, durch MRT nachgewiesenen Veranderungen—multiple fokale Lasionen und ausgepragter Hydrozephalus—waren nach BSCT rucklaufig. Zum Zeitpunkt der BSCT, die im Alter von 19 bzw. 32 Monaten durchgefuhrt wurde, wiesen beide Kinder eine psychomotorische Retardierung auf und zeigten die typischen Stigmata des Hurler-Syndroms. Aktuell sind beide Patienten in ambulanter Betreuung, eine Graft-versus-host-disease (GvHD) wurde nicht gesehen. Sie haben eine stabile Transplantatfunktion ohne rezidivierende Infektionen wie vor BSCT.

ZusammenfassungDie klinische Trias der immuno-ossären Dysplasie Schimke (IODS) besteht aus spondyloepiphysärer Dysplasie, Nephropathie und Immunopathie. Neurologische Symptome sind bei >50% der Patienten mit IODS nachweisbar. Beschrieben wurden Kopfschmerzen, Doppelbilder, motorische Aphasien, Hemiparästhesien und Hemiparesen, die auf transitorische ischämische Attacken oder Hirninfarkte auf der Basis einer frühen generalisierten Arteriosklerose zurückgeführt werden. Trotz erfolgreicher Nierentransplantation kann es zu neurologischen Symptomen kommen; das transplantierte Organ bleibt von pathologischen Veränderungen verschont. Das Auftreten neurologischer Symptome scheint mit der Schwere der Erkrankung zu korrelieren. Eine Phänotyp-Genotyp-Korrelation besteht insofern, als klinisch schwerer betroffene IODS-Patienten auf beiden Allelen nonsense-, frame-shift-oder splicing-Mutationen des SMARCAL1-Gens aufweisen, wohingegen Patienten mit milden Verläufen missense-Mutationen auf jedem Allel zeigen. Eine wirksame Therapie der IODS und auch der neurologischen Symptome existiert bislang nicht. Die zugrundeliegende Pathologie der Erkrankung bleibt trotz bekanntem Gendefekt unklar.

We report on an otherwise healthy infant who presented with clusters of alternating central facial nerve paresis. At 11 months of age, the patient showed intermittent facial asymmetry compatible with right-sided upper motor neuron facial paresis and accompanying incomplete upper motor neuron hypoglossal paresis. Laboratory work-up and imaging studies did not reveal signs of infection, infarction or structural lesions, and after one week, symptoms spontaneously resolved. Similar episodes affecting alternate sides were noted at ages of 17, 27 and 49 months lasting for 4-14 days. At 49 months, EEG showed right temporo-occipital benign sharp waves with activation during drowsiness and sleep. A diagnosis of benign focal epilepsy with negative motor phenomena was made. She is now 60 months old and no further episodes have occurred without antiepileptic treatment. Ictal orofacial phenomena are the clinical hallmark of benign focal epilepsy with centro-temporal sharp waves (BECTS). As in our patient, negative epileptic motor phenomena frequently lead to a broad diagnostic work-up. In infants presenting with episodic central facial nerve paresis, the possibility of negative epileptic motor phenomena should be considered.

Background Isolated optic neuritis (ON) in childhood may remain a single episode or mark the clinical beginning of multiple sclerosis (MS). Higher age and pathological cranial MRI (cMRI) at presentation were previously demonstrated as independent risk factors of conversion to MS. Objective To further evaluate potential MS risk factors, including cerebrospinal fluid findings (CSF), in children with ON as a first demyelinating event. Methods Children with isolated uni- or bilateral ON as a first demyelinating event below age 18 were included in this retrospective multicenter cohort study. The minimal follow-up (FU) for those not converting to MS according to McDonald 2010 was 2 years. Age, sex, laterality of ON, cMRI (no vs ≥1 MS-compatible lesion outside the optic nerves) and intrathecal oligoclonal IgG bands (OCB) were assessed as risk factors using simple and multiple Cox proportional-hazards regressions. Results Of 357 included children 284 had uni- and 73 bilateral isolated ON. Median FU of patients not developing MS was 4.2 years (range 2.0–22.0). Univariate analyses revealed age (HR 1.15, 95% CI 1.10–1.22, p Conclusion Cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON as a first demyelinating event.