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

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

Qualitative and quantitative muscle ultrasound in patients with Duchenne muscular dystrophy: Where do sonographic changes begin?

OBJECTIVE: The number of studies investigating and understanding the disease mechanisms of Duchenne muscular dystrophy (DMD) in human clinical trials have increased substantially over the last decade. Suitable clinical instruments for the measurement of disease progress and drug efficiency are mandatory, but currently not available, especially in the youngest patients. The aim of this study was to detect a reproducible pattern of muscle involvement in early stages potentially preceding evidence of motor regression. MATERIAL AND METHODS: A cohort of 25 DMD patients aged 1-6 years at the first presentation were examined at multiple timepoints and compared with age-matched healthy controls. Muscle ultrasound was quantified using computer-analyzed gray scale levels (GSL) and blinded visual rating, using a modified Heckmatt scale. RESULTS: Changes in muscle echogenicity in DMD patients occurred very early, clearly preceding motor regression and in some cases, even before the motor plateau phase was reached. Visual rating and GSL identified the earliest changes in the proximal adductor magnus muscle. CONCLUSION: Muscle ultrasound can be used as an additional method to assess the disease progression and for decision-making in paucisymptomatic DMD patients. Sonographic changes in the ad-ductor magnus muscle seem to be the first detectable changes with a recognisable pattern.

Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review.

BACKGROUND: KCNQ2 related disorders comprise both benign seizure disorders and early onset epileptic encephalopathies. Especially within the latter group, patients suffer from refractory seizures to standard antiepileptic drugs and developmental delay. Besides the hope of personalized medical approaches to treat the recently unraveled large amount of genetic channelopathies, there are sparse systematic data on treatment responses in KCNQ2 related epilepsy in larger cohorts. METHODS: We searched PubMed using the free text term search 'KCNQ2 AND Epilepsy' and identified additional records using PubMed Medical Subject Headings (MeSH). Based on patients' clinical information about their therapy they were assigned to one of four groups: 'seizure freedom', 'responder', 'successful therapy', and 'unsuccessful therapy'. RESULTS: Out of 52 studies, 217 subjects were eligible for further data analyses. 133 patients were classified as 'benign' seizure disorders whereas 84 patients were classified as 'Early Onset Epileptic Encephalopathy (EOEE)'. In the 'benign' group, 92.5% of patients became seizure free while 3.8% did not respond to treatment. In contrast 65.5% of patients in the 'EOEE' group were reported seizure free, while 14.3% showed no treatment success (p = 0.003). Spontaneous seizure remission (without medication) was 30.1% in the 'benign' group. Phenobarbital and sodium channel blockers most often lead to seizure freedom in patients with a 'benign' course. In patients with 'EOEE' seizure freedom was more likely achieved when receiving sodium channel blockers. CONCLUSIONS: Seizures associated with mutations within the voltage gated potassium channel KCNQ2 are well controlled by medical treatment in patients with 'benign' courses and moderately well in patients with the 'EOEE' group. A significant number of patients in the 'benign' group may experience seizure freedom spontaneously. Phenobarbital might be considered in benign courses, while sodium channel blockers seem appropriate for both 'benign' and 'EOEE' patients.

Three by three weeks of robot-enhanced repetitive gait therapy within a global rehabilitation plan improves gross motor development in children with cerebral palsy - a retrospective cohort study.

AIM: To assess the improvement in gross motor function following three blocks of a three-week, intensive robot-enhanced treadmill therapy (ROBERT-Program). METHOD: retrospective chart review in a before-after interventional trial in children with cerebral palsy attending a university hospital outpatient rehabilitation centre. Patients received three blocks of a three-week, 12 sessions ROBERT-Program over a mean period of 24 months. Outcome measures were block specific and cumulative improvement in GMFM 66, D and E. Longterm GMFM 66 improvements were compared to the individuals' expected increment as derived from previously published GMFM-66 percentiles. 95% confidence intervals (CI) and paired t-test were calculated. RESULTS: 20 children (8 GMFCS Level II; 12 GMFCS Level III, mean age 5.9 years (CI: [5.0; 6.7])) were treated. For each block a significant increase in motor performance in similar size could be observed without deterioration between blocks. The cumulative improvement during 21 months observation period was: 6.5 (CI: [4.8; 8.2]) in GMFM 66, which represents a clinically meaningful effect size of 3.6 (CI: [1.4; 5.8]) above the expected improvement. INTERPRETATION: Progressive clinically meaningful improvement in motor performance for three blocks of ROBERT-Program was observed. Cumulative GMFM 66 improvements exceeded the individuals' age-specific expected course.

Children with migraine: Provocation of headache via pressure to myofascial trigger points in the trapezius muscle? - A prospective controlled observational study.

BACKGROUND: The objective was to evaluate a supposed clinical interdependency of myofascial trigger points and migraine in children. Such interdependency would support an interaction of spinal and trigeminal afferences in the trigemino-cervical complex as a contributing factor in migraine. METHODS: Children ≤18 years with the confirmed diagnosis of migraine were prospectively investigated. Comprehensive data on medical history, clinical neurological and psychological status were gathered. Trigger points in the trapezius muscle were identified by palpation and the threshold of pressure pain at these points was measured. Manual pressure was applied to the trigger points, and the occurrence and duration of induced headache were recorded. At a second consultation (4 weeks after the first), manual pressure with the detected pressure threshold was applied to non-trigger points within the same trapezius muscle (control). Headache and related parameters were again recorded and compared to the results of the first consultation. RESULTS: A total of 13 girls and 13 boys with migraine and a median age of 14.5 (Range 6.3-17.8) years took part in the study. Manual pressure to trigger points in the trapezius muscle led to lasting headache after termination of the manual pressure in 13 patients while no patient experienced headache when manual pressure was applied to non-trigger points at the control visit (p < 0.001). Headache was induced significantly more often in children ≥12 years and those with internalizing behavioural disorder. CONCLUSION: We found an association between trapezius muscle myofascial trigger points and migraine, which might underline the concept of the trigemino-cervical complex, especially in adolescents. SIGNIFICANCE: In children with migraine headache can often be induced by pressure to myofascial trigger points, but not by pressure to non-trigger points in the trapezius muscle. This supports the hypothesis of a trigemino-cervical-complex in the pathophysiology of migraine, which might have implications for innovative therapies in children with migraine.

Early-Onset Myopathies: Clinical Findings, Prevalence of Subgroups and Diagnostic Approach in a Single Neuromuscular Referral Center in Germany.

BACKGROUND: Early-onset myopathies are a heterogeneous group of neuromuscular diseases with broad clinical, genetic and histopathological overlap. The diagnostic approach has considerably changed since high throughput genetic methods (next generation sequencing, NGS) became available. OBJECTIVE: We present diagnostic subgroups in a single neuromuscular referral center and describe an algorithm for the diagnostic work-up. METHODS: The diagnostic approach of 98 index patients was retrospectively analysed. In 56 cases targeted sequencing of a known gene was performed, in 44 patients NGS was performed using large muscle specific panels, and in 12 individuals whole exome sequencing (WES) was undertaken. One patient was diagnosed via array CGH. Clinical features of all patients are provided. RESULTS: The final diagnosis could be found in 63 out of 98 patients (64%) with molecular genetic analysis. In 55% targeted gene sequencing could establish the genetic diagnosis. However, this rate largely depended on the presence of distinct histological or clinical features. NGS (large myopathy-related panels and WES) revealed genetic diagnosis in 58.5% (52% and 67%, respectively). The genes detected by WES in our cohort of patients were all covered by the panels. Based on our findings we propose an algorithm for a practical diagnostic approach.Prevalences:MTM1- and LAMA2-patients are the two biggest subgroups, followed by SEPN1-, RYR1- and Collagen VI-related diseases. 31% of genetically confirmed cases represents a group with overlap between "congenital myopathies (CM)" and "congenital muscular dystrophies (CMD)". In 36% of the patients a specific genetic diagnosis could not be assigned. CONCLUSIONS: A final diagnosis can be confirmed by high throughput genetic analysis in 58.5% of the cases, which is a higher rate than reported in the literature for muscle biopsy and should in many cases be considered as a first diagnostic tool. NGS cannot replace neuromuscular expertise and a close discussion with the geneticists on NGS is mandatory. Targeted candidate gene sequencing still plays a role in selected cases with highly suspicious clinical or histological features. There is a relevant clinical and genetic overlap between the entities CM and CMD.

[Childhood stroke : What are the special features of childhood stroke?] / "Childhood stroke" : Was macht den Schlaganfall beim Kind besonders?

Childhood arterial ischemic stroke differs in essential aspects from adult stroke. It is rare, often relatively unknown among laypersons and physicians and the wide variety of age-specific differential diagnoses (stroke mimics) as well as less established care structures often lead to a considerable delay in the diagnosis of stroke. The possible treatment options in childhood are mostly off-label. Experiences in well-established acute treatment modalities in adult stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in children and only based on case reports and case series. The etiological clarification is time-consuming due to the multitude of risk factors which must be considered. Identifying each child's individual risk profile is mandatory for acute treatment and secondary prevention strategies and has an influence on the individual outcome. In addition to the clinical neurological outcome the residual neurological effects of stroke on cognition and behavior are decisive for the integration of the child into its educational, later professional and social environment.

[Epilepsy-new diagnostic tools, old drugs? : Therapeutic consequences of epilepsy genetics]. / Epilepsie ­ neue Diagnostik, alte Medikamente? : Die Konsequenzen der Epilepsiegenetik.

BACKGROUND: Recent advances in the field of epilepsy genetics have led to an increased fraction of patients with epilepsies where the etiology of the disease could be identified. Nevertheless, there is some criticism regarding the use of epilepsy genetics because in many cases the identification of a pathogenetic mutation does not lead to an adaptation of therapy or to an improved prognosis. In addition, the interpretation of genetic results might be complicated due to the considerable numbers of variants of unclear significance. OBJECTIVE: This publication presents the arguments in favour of a broad use of genetic investigations for children with epilepsies. Several diseases where a genetic diagnosis does in fact have direct therapeutic consequences are mentioned. In addition, the indirect impact of an established etiology, encompassing the avoidance of unnecessary diagnostic measures, possibility of genetic counselling, and the easing of the psychologic burden for the caregivers, should not be underestimated. CONCLUSION: The arguments in favour of broad genetic diagnostics prevail notwithstanding the lack of relevant new developments regarding the therapy.

Proximal muscular atrophy and weakness: An unusual adverse effect of deferasirox iron chelation therapy.

Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug.