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Background Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce. Methods In the VRONI study, children aged 5–14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members. Results Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024. Conclusions VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).

As IQ tests are commonly used as key assessment method, we address the question whether our commonly used standardized IQ tests are appropriate for children from families of diverse cultures and different educational levels in a refugee population. We examined 109 refugee children aged 3–7 years (M = 5.10 years, SD = 1.25) with the “Kaufman Assessment Battery for Children “ (KABC-II; Kaufmann & Kaufmann, 2015) on a language-free scale (Scale of Intellectual Functioning, SIF) and learning performance (subtest Atlantis). With a non-verbal IQ of 81.5 (SD = 18.01), the population mean of the refugee children is more than one standard deviation lower than the mean of the German norm population. Standardized scores follow the normal distribution and are not correlated to any of the assessed markers of adversity (flight duration, time spent in Germany, child PTSD in parent rating, parental symptom load, and parental education level).Conclusion: The interpretation of IQ test results for refugee children should be done cautiously as results may underestimate their cognitive capacity. Environmental factors, such as high illiteracy among parents in this study, the lack of institutional education of children and high lifetime stress, may explain our findings.Trial registration: DRKS00021150. What is Known:• There is a high pervasiveness for the use of standardized IQ tests in the German health and education system to determine eligibility for special education and social services. What is New:• Refugee children score significantly lower than German children in a language-free IQ test. As results are normally distributed and not correlated to any of the assessed markers of adversity, the low scores in the refugee group might be due to missing formal education.

This review summarizes the state of knowledge of use of new media on the development in early childhood in 6 sections: descriptive utilization data, psychosocial and emotional development, cognition and language, motor development, nutrition and sleep, and influence of parental media consumption.The review is based on a literature search of this topic in peer-reviewed journals. We included 87 articles, books, and book chapters. The used literature data bases were ERIC, PsycARTICLES, PsycINFO and PSYNDEX.Manifold studies describe in young children's utilization data the pervasive nature of digital exposure and impressive usage times and availability. They confirm adverse influences of electronic media use (television, video games) on children's emotional and behavioral problems and well-being, e. g. on physical activity, sleep and obesity. In general a positive effect in sense of knowledge transfer of age could be found for high quality educational media, however predominantly the impact of media use at younger age was negative.High frequent media use in early childhood is likely to have a negative impact on psychosocial development, positive effects such as knowledge transfer may be seen beyond the age of 18 months. As parental media use is a strong predictor of child media habits, reducing parental media use and enhancing parent-child interactions might be important areas to address when trying to change the media behavior of young children. In view of the scarcity of studies for early childhood, it is advisable to use digital play and communication devices cautiously and restrictively in this vulnerable development phase.Dieses Review fasst den aktuellen Wissensstand zum Gebrauch neuer Medien in der frühen Kindheit für 6 Bereiche zusammen: Deskriptive Gebrauchsdaten, psychosoziale und emotionale Entwicklung, Kognition und Sprache, motorische Entwicklung, Ernährung und Schlaf, Einfluss des elterlichen Medienkonsums.Das Review basiert auf einer Literaturrecherche in peer reviewed Zeitschriften. Insgesamt wurden 87 Artikel, Bücher und Buchkapitel eingeschlossen. Durchsucht wurden die Literaturdatenbänke ERIC, PsycARTICLES, PsycINFO und PSYNDEX.Die Studien dokumentieren die Allgegenwärtigkeit der Mediennutzung im frühen Lebensalter und weisen eindrucksvolle Nutzungszeiten und Verfügbarkeiten auf. Sie bestätigen ungünstige Einflüsse der elektronischen Medien (Fernseher, Videospiele) auf emotionale und Verhaltensprobleme und auf das Wohlergehen der Kinder, wie z. B. körperliche Aktivität, Schlaf und Übergewicht. Es konnten auch positive Einflüsse von pädagogisch hochwertigen Medien identifiziert werden. Jedoch überwiegen die negativen Effekte der Mediennutzung im jungen Alter deutlich.Ein hoher Medienkonsum in der frühen Kindheit hat negative Auswirkungen auf die psychosoziale Entwicklung, wohingegen positive Effekte wie bspw. Wissenstransfer erst ab einem Alter von 18 Monaten beobachtet werden können. Eine reduzierte Nutzung seitens der Eltern und eine verbesserte Eltern-Kind Interaktion sind wichtige Bereiche für eine Veränderung der kindlichen Mediennutzung. Wegen des Mangels an Studien ist es ratsam digitale Spiel- und Kommunikationsgeräte nur mit Vorsicht zu nutzen.

Background Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. Objectives We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). Methods We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. Results Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. Conclusions The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

PURPOSEBi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus.METHODSThrough an international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms.RESULTSA cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections and central/nocturnal hypopnea as core manifestations. A review of brain MRI scans demonstrated a thin corpus callosum in 52%. We evaluated 17 distinct variants. Missense variants in TECPR2 are predominantly located in the N- and C-terminal regions containing β-propeller repeats. Despite constituting nearly half of disease associated TECPR2 variants, classifying missense variants as (likely) pathogenic according to ACMG criteria remains challenging. We estimate a pathogenic variant carrier frequency of 1/1,221 in the general and 1/155 in the Jewish Ashkenazi populations.CONCLUSIONBased on clinical, neuroimaging and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/treatment of individuals with TECPR2-associated disorder. This sets the stage for future prospective natural history studies.CONFLICTS OF INTERESTAll authors involved in the study declare no conflicts of interest relevant to this study.

Summary Background Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. Methods For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. Findings We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. Interpretation In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. Funding Else Kroner-Fresenius-Stiftung, Technische Universitat Munchen, Helmholtz Zentrum Munchen, Medizinische Universitat Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.

This study aims to evaluate the effectiveness of a prefabricated carbon-composite ankle foot orthoses (c-AFOs) on gait parameters in children with unilateral spastic cerebral palsy (USCP) exhibiting a drop foot pattern.Sixteen ambulatory children with USCP and a drop foot pattern were included (mean age: 9 years; gross motor function classification system: I = 14, II = 2) and three-dimensional gait analysis was applied under randomly assigned conditions (barefoot; shoe; c-AFO). Kinematics, kinetics, time-distance parameters and gait indices were investigated.Effects on the drop foot pattern were investigated while the children walked in shoes only. The shoes already increased the maximum ankle dorsiflexion in swing (p= 0.004) and initiated more knee flexion during single support (p⩽ 0.013). Compared to shoe walking, the c-AFO led to additional benefits regarding further ankle dorsiflexion during swing (p⩽ 0.001) and initial contact (p0.001), ankle movement during loading response (p= 0.002), improved the sole angle during initial contact (p0.001) and during mid stance (p= 0.015). Plantarflexion and ankle power generation during push-off decreased when wearing the c-AFO (p⩽ 0.008).Investigated c-AFOs are beneficial for improving drop foot patterns in children with USCP. Significant effects on pathological barefoot pattern were already achieved with the child's regular shoes. This could be considered in clinical decision processes. In comparison to shoe walking, c-AFO additionally improved foot clearance and normalized initial heel contact. The third rocker deteriorates with the c-AFO. Since kinematics improved with the orthoses during swing and early stance phase, c-AFOs might reduce tripping and falling caused by a drop foot during long distance walking.

Mitochondrial dynamics such as fission and fusion play a vital role in normal brain development and neuronal activity. DNM1L encodes a dynamin-related protein 1 (Drp1), which is a GTPase essential for proper mitochondrial fission. The clinical phenotype of DNM1L mutations depends on the degree of mitochondrial fission deficiency, ranging from severe encephalopathy and death shortly after birth to initially normal development and then sudden onset of refractory status epilepticus with very poor neurologic outcome. We describe a case of a previously healthy 3-year-old boy with a mild delay in speech development until the acute onset of a refractory status epilepticus with subsequent epileptic encephalopathy and very poor neurologic outcome. The de novo missense mutation in DNM1L (c.1207C > T, p.R403C), which we identified in this case, seems to determine a unique clinical course, strikingly similar to four previously described patients in literature with the identical de novo heterozygous missense mutation in DNM1L.

Several controlled studies have shown that in children with cerebral palsy, botulinum toxin A (BTX/A) can decrease muscular hyperactivity associated with spasticity and improve function. Studies have hitherto focused on the dimensions of impairment and functional limitations. In this pilot study with BTX/A in children with cerebral palsy, we used the Pediatric Evaluation of Disability Inventory (PEDI) to evaluate the effect of treatment. PEDI is a reliable and valid instrument that focuses on assessing disability in daily life. Patients with cerebral palsy (n = 17, median age 5.5 years, age range 2.5 to 16.5 years) were treated with BTX/A for pes equinus (n = 8) or adductor spasm (n = 9). PEDI assessment was carried out before and 1 month after the first treatment with BTX/A. Scaled scores were calculated according to the user’s manual for the Mobility domain with scores near „0” reflecting low capability and scores near „100” reflecting high capability. We found a significant improvement in the mobility domain-caregiver dimension from 52.3% ± 26.6% to 56.6% ± 26.7% (mean, standard deviation P < 0.05), as well as in the self care domain-functional skills from 63.6% ± 18.7% to 65.2% ± 19.6% (mean, standard deviation P < 0.05). Our data indicate that in young patients with cerebral palsy, BTX/ A therapy of the lower extremity can reduce the disability. For these patients PEDI is a valuable assessment instrument that reflects the effect of treatment with BTX/A on the disability. (J Pediatr Neurol 2003; 1(1): 29-34).

Der Einsatz bildgebender Verfahren und neurophysiologischer Techniken erlaubt in zunehmendem Mase die Exploration neuroplastischer Veranderungen, wie sie moglicherweise infolge einer Intervention im zentralen Nervensystem (ZNS) auftreten konnen. Dies wird anhand von Laufbanduntersuchungen zur Pathophysiologie des Ganges, zur robotergestutzten Laufbandtherapie (Lokomat®) und fur die obere Extremitat exemplarisch fur die „constraint induced movement therapy“ (CIMT) – Behandlungen, die sich durch Aufgabenspezifitat und Zielorientierung auszeichnen – dargestellt. Sowohl auf spinaler als auch auf kortikaler Ebene lassen sich durch die Interventionen hervorgerufene Veranderungen nachweisen und Unterschiede im Ansprechen auf die Therapie in Abhangigkeit des Lasions- und Reorganisationstyps darstellen. Dies belegt, dass eine aufgabenspezifische Plastizitat des ZNS bei Patienten mit Zerebralparese vorhanden ist und dass in klinischen Studien systemphysiologische Untersuchungen und Erkenntnisse als Stratifizierung- oder Evaluationsinstrument Berucksichtigung finden sollten.

An interdisciplinary group of German experts in the field of movement disorders was as- sembled under the auspices of the Society for Neuropediatrics to develop a graphically based guideline for a multidisciplinary treat- ment regime in the management of motor dysfunction in children with bilateral spastic cerebral palsy (BS-CP). The present consensus was accomplished by a cooperation includ- ing neuroscience and rehabilitation medicine. The aim of the "treatment curves CP-motor development" is to present age- and severi- ty-specific therapy options for the treatment of motor dysfunction in children with BS- CP on the basis of the GMFCS development

Unilateral thalamic infarction is a rare condition in adults. This is a case report of a young child presenting with left-sided hemiparesis of sudden onset due to an unilateral venous thalamic infarction. This was attributed to an asymmetric thrombosis of the cerebral internal veins, a partial thrombosis of the vein of Galen and straight sinus. Magnetic resonance imaging resulted primarily in the differential diagnosis of a cerebral tumor or an intracerebral abscess, leading to stereotactic puncture. Subsequent magnetic resonance venography facilitated the correct diagnosis. Heparin-induced thrombocytopenia necessitated anticoagulation treatment with hirudin and later, warfarin. The patient made a complete recovery. We conclude that unclear unilateral thalamic lesions might be symptomatic of a cerebral deep venous thrombosis and might mimic a thalamic tumor. In uncertain cases, we suggest rapid performance of magnetic resonance angiography.

The aim of the present study was to investigate corticospinal and intracortical excitability in patients with congenital stroke. In adults, stroke sequelae reduce corticospinal excitability, as indicated by an elevated threshold for motor evoked potentials (MEP), and increase intracortical excitability, as indicated by reduced intracortical inhibition. Ten patients with pre- or perinatally acquired, unilateral cortico-subcortical infarctions in the middle cerebral artery territory were studied with single pulse transcranial magnetic stimulation (TMS) to measure motor threshold (MT) and with paired pulse TMS to study short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Eight healthy, age-matched subjects served as controls. MT over the affected hemisphere of patients compared with the dominant hemisphere of controls was significantly elevated, reflecting reduced corticospinal excitability, and SICI was significantly reduced, reflecting increased intracortical excitability. No such differences were found for ICF. Findings in patients with congenital stroke were comparable with adulthood stroke. Thus, similar assumptions can be made: reduced corticospinal excitability is probably a consequence of neuronal damage. Reduced intracortical inhibition might represent deficient inhibitory cortical properties or might reflect a compensational mechanism, dispositioning for use-dependent plasticity.

Die klinische Neurophysiologie bedient sich einer Vielzahl von funktionellen und strukturellen Methoden zur Erforschung des sich entwickelnden Gehirns. Die physiologischen Korrelate motorischen Lernens, neuronaler Plastizitat und deren Regulationsmechanismen lassen sich methodisch identifizieren und in ihrer Reifungsdynamik am sich entwickelnden Gehirn darstellen. Die neurophysiologischen Grundlagen komplexer Handlungsablaufe sind funktionell und bildgebend evaluiert und weisen eine signifikante Reifungsdynamik auf. Somit gelingt es der klinischen Neurophysiologie, der Beobachtung, dass Lernvorgange und die Ausfuhrung komplexer Handlungsablaufe einer Reifungsdynamik unterliegen, funktionelle und strukturelle Korrelate des sich entwickelnden Gehirns zuzuordnen.

Background Repetitive peripheral magnetic stimulation (rPMS) has been applied to musculoskeletal pain conditions. Since recent data show that migraine and tension-type headache (TTH) might be closely related to peripheral muscular pain in the neck and shoulder region (supporting the concept of the trigemino-cervical complex (TCC)), this pilot study explores the acceptance of rPMS to the upper trapezius muscles in migraine (partly in combination with TTH). Methods We used rPMS to stimulate active myofascial trigger points (aTrPs) of the upper trapezius muscles in 20 young adults suffering from migraine. Acceptance was assessed by a standardized questionnaire, whereas self-rated effectiveness was evaluated by headache calendars and the Migraine Disability Assessment (MIDAS). Algometry was performed to explore the local effect of rPMS on the muscles. Results Acceptance of rPMS was shown in all subjects without any adverse events, and rPMS had a statistically significant impact on almost every parameter of the headache calendar and MIDAS. Among others, the number of migraine attacks ( p p = 0.001) significantly decreased regarding pre- and post-stimulation assessments. Accordingly, 100.0% of subjects would repeat the stimulation, while 90.0% would recommend rPMS as a treatment option for migraine. Conclusions rPMS might represent a promising tool to alleviate migraine symptoms within the context of myofascial pain. This might be due to stimulation-dependent modulation of the peripheral sensory effect within the TCC in migraine. However, sham-controlled studies with larger and more homogeneous cohorts are needed to prove a potential beneficial effect. Ethics Committee Registration Numbers : 356-14 and 447/14

In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.

We aimed to translate the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire into German and to evaluate its reliability and validity by studying the association between CPCHILD scores and gross motor function as measured by the gross motor function classification system (GMFCS) in children with cerebral palsy (CP). The original CPCHILD questionnaire and manual were translated and back translated. It was administered to primary caregivers of persons with CP (GMFCS levels III–V) and was completed a second time 2 weeks after the first to measure test–retest reliability ( n = 17). Primary caregivers of 68 children with CP; GMFCS level III ( n = 14), level IV ( n = 28), and level V ( n = 26) completed the questionnaire. Mean total CPCHILD scores across GMFCS levels were 67.1 ± 14.9 for GMFCS level III, 56.6 ± 11.8 for level IV, and 44.3 ± 12.9 for level V. Good correlation ( r = − 0.56) was observed between GMFCS and total scores test–retest reliability showed intraclass correlation coefficients between 0.4 and 0.9. The German CPCHILD yielded similar test–retest reliability and score distributions across the GMFCS level as the original version. The best correlations were observed for domains that are close to the functional deficits.

Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere.We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis.Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD).DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume.The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers.

One of the main goals when treating spasticity is to relieve pain and improve function. Intramuscular injection of botulinum toxin type A (BTX-A) has gained widespread acceptance in the treatment of spastic cerebral palsy. Several studies have clearly shown the short-term functional benefit of BTX-A treatment. Information is limited, however, on the efficacy of medium and long-term regimens, using repeated injection of BTX-A. The aim of the present open-label, prospective study was to evaluate functional outcome in children with spastic cerebral palsy after 1 year of treatment with BTX-A, using the Gross Motor Function Measure (GMFM) as a validated outcome measure. Patients (n=25, age 1.5--15.5 years) were treated with BTX-A for adductor spasm (n=12) or pes equinus (n=13). The local effect was evaluated using passive range of motion and modified Ashworth Scale. Apart from a significant improvement in joint mobility and reduction of spasticity compared to pretreatment values (P < 0.01), we demonstrated a significant improvement of gross motor function after 12 months of treatment, with a median gain of 6% in total and goal scores (P < 0.001). An increase in GMFM scores was particularly evident in younger and moderately impaired children (Gross Motor Function Classification System level III). Whether the observed improvement in gross motor function in children with cerebral palsy is specifically related to therapy with BTX-A or represents at least in part the natural course of motor development still needs clarification.

Objective To examine whether, and if so, how psychosocial topics are discussed between parents and pediatricians. Methods Thirty well-child visits at eight pediatricians’ practices in southwest Germany were video recorded. Conversations were analyzed. Results Although psychosocial topics were frequently touched upon, they were rarely thoroughly explored. Pediatricians pursued a rather reserved conversation style. Especially when parents withdraw and psychosocial stressors are less baby-related, pediatricians hardly explore the psychosocial situation. Conclusion In summary, the pediatrician's conversation style, the nature of the stressors and the parents’ openness are paramount in determining the depth of psychosocial exploration. Practice implications In order to ensure a good and fair quality of care to all parents, pediatricians should be provided with tailored communicative skills training allowing them to create a climate in which parents may open up and build trust toward their pediatrician.

Das zum Medikament gewordene Toxin etablierte sich spater als Therapie der Wahl in der Erwachsenenneurologie fur den Torticollis spasmodicus, den Blepharospasmus und den Hemispasmus facialis. Die intramuskulare Injektion von Botulinum-Toxin A gilt hier als effektives, sicheres und nebenwirkungsarmes Therapieverfahren. Seit Beginn der 90er Jahre liegen Erfahrungen bei der Anwendung von Botulinum-Toxin A bei spastischen Bewegungsstorungen im Kindesalter vor. Chancen und Grenzen dieser therapeutischen Moglichkeit sollen – gemeinsam mit den korrespondierenden Erfahrungen aus der Neurologie – dargestellt werden.

Aims: Macrocerebellum is a very rare finding and implies an abnormally large cerebellum. Only few patients with a syndromal or isolated macrocerebellum have been reported so far. We aim to evaluate the MRI spectrum, objectify the macrocerebellum by volumetric analysis, characterize neurological/dysmorphic features and cognitive outcome and report genetic analysis. Methods: All images were qualitatively evaluated for infra- and supratentorial abnormalities. A volumetric analysis was performed using MRI Studio software. Data about neurological and dysmorphic features, outcome and genetic analysis were collected from clinical history and follow-up examination. Results: 5 children were included (median age 2.5 years, range 1–3 years; 3 males, 2 females). The volumetric analysis in 3 patients confirmed the increased cerebellar size compared to age matched controls (in the 2 other patients the volumetric analysis could not be performed). The MRI evaluation showed that an enlargement of the cortical gray matter of the cerebellar hemispheres was mainly contributing to the macrocerebellum. Different additional infra- and supratentorial abnormalities were present in all patients. Muscular hypotonia, ocular movement disorders and impaired motor and cognitive development were found in all children. 3 of 5 patients suffered from epileptic seizures. The 5 children differed significantly in terms of dysmorphic features and involvement of extra-cerebral organs. Chromosomal anomalies were found in 2 patients (a deletion and a duplication on different chromosomes). Conclusion: Based on the literature and our study, all patients with a macrocerebellum have variable impairments in motor and cognitive development. However, the additional neuroimaging findings, dysmorphic features, involvement of extra-cerebral organs and genetic results are highly heterogeneous, suggesting that macrocerebellum is not a clinical and neuroimaging entity.

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.