Childhood haemorrhagic stroke: a 7-year single-centre experience

BACKGROUND: In recent years, there has been increasing research interest in improving diagnostic and management protocols in childhood arterial ischaemic stroke (AIS). However, childhood stroke comprises, in approximately equal parts, both arterial ischaemic and haemorrhagic stroke (HS). // OBJECTIVE: The aim of this study was to focus on the aetiology, clinical presentation, treatment and short-term outcome of children with spontaneous intracranial bleeding in a university hospital and elucidate differences to childhood AIS. // DESIGN: We performed a retrospective analysis of electronic medical records of children (28 days-18 years) diagnosed with HS between 2010 and 2016. // RESULTS: We included 25 children (male child, n=11) with a median age of 8 years 1 month. The most common clinical presentations were vomiting (48%), headache (40%) and altered level of consciousness (32%). In more than half of the patients, HS was caused by vascular malformations. Other risk factors were brain tumour, coagulopathy and miscellaneous severe underlying diseases. Aetiology remained unclear in one child. Therapy was neurosurgical in most children (68%). Two patients died, 5 patients needed further (rehabilitation) treatment and 18 children could be discharged home. // CONCLUSIONS: HS differs from AIS in aetiology (vascular malformations as number one risk factor), number of risk factors ('mono-risk' disease), clinical presentation (vomiting, headache and altered level of consciousness) and (emergency) therapy

Health-Related Quality of Life after Pediatric Traumatic Brain Injury: A Quantitative Comparison between Children’s and Parents’ Perspectives of the QOLIBRI-KID/ADO Questionnaire

Pediatric health-related quality of life (HRQoL) as a measure of subjective wellbeing and functioning has received increasing attention over the past decade. HRQoL in children and adolescents following pediatric traumatic brain injury (pTBI) has been poorly studied, and performing adequate measurements in this population is challenging. This study compares child/adolescent and parent reports of HRQoL following pTBI using the newly developed Quality of Life after Brain Injury in Children and Adolescents (QOLIBRI-KID/ADO) questionnaire. Three hundred dyads of 8–17-year-old children/adolescents and their parents were included in the study. The parent–child agreement, estimated using intraclass correlation coefficients and Cohen’s κ, displayed poor to moderate concordance. Approximately two-fifths of parents (39.3%) tended to report lower HRQoL for their children/adolescents on the total QOLIBRI-KID/ADO score. At the same time, about one-fifth (21.3%) reported higher HRQoL Total scores for their children/adolescents. The best agreement for parents rating adolescents (aged 13–17 years) was found in terms of the Total score and the Cognition and Self scale scores. To date, parent-reported HRQoL has been the preferred choice in pediatric research after TBI. However, with a parent–child disagreement of approximately 60%, our results highlight the importance of considering self-reports for children/adolescents capable of answering or completing the HRQoL measures

Monogenic variants in dystonia: an exome-wide sequencing study

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

Botulinumtoxin (BTX) Biologisches Prinzip und Medikament interventioneller Neuropädiatrie

Bis vor wenigen Jahren war Botulinumtoxin (BTX) dem Pädiater ausschließlich als Ursache des Säuglingsbotulismus bekannt. In der Erwachsenenneurologie wurde es bereits vor 25 Jahren eingeführt. Die Neuropädiatrie hat es seit etwa 15 Jahren als wirksames, sicheres und reversibles Medikament für Kinder etabliert. Von den 7 verschiedenen Serotypen wird prädominant Serotyp A, in geringerem Umfang auch B eingesetzt. BTX hemmt temporär die cholinerge Transmission. Die zur Verfügung stehenden Präparate (BTX-A: BOTOX, Dysport; BTX-B: NeuroBloc) haben für das Kindesalter spezifische Wirkprofile. Sie sind nicht schematisch austauschbar und bedürfen besonderer Anwenderkenntnis. Die Einführung von BTX in die Behandlung der Cerebralparesen (CP) ist ein wesentlicher, evidenzbasierter und international bestätigter Therapiefortschritt der letzten Jahre. Die Option BTX sollte für jedes Kind mit einer CP kompetent diskutiert und entschieden werden: nicht als isolierte Therapieoption, sondern als Bestandteil eines entwicklungsneurologisch adaptierten, interdisziplinären Therapiekonzepts. Der Dialog zwischen den BTX in der Pädiatrie einsetzenden Disziplinen (Neuropädiatrie, Sozialpädiatrische Zentren, Pädiatrische Rehabilitation, Neurologie, Kinderorthopädie) wird es erlauben, das Indikationsspektrum auszuweiten und das therapeutische Vorgehen zu standardisieren.Not many years have passed since paediatricians only thought of botulinum toxin (BTX) as the agent responsible for infant botulism. Although introduced 25 years ago as a drug for treating certain neurological disorders in adults, it is only in the past 15 years that paediatric neurologists have established BTX as an effective and safe medication (with a dependably reversible mode of action) for the treatment of children. There are seven distinct BTX serotypes of which predominantly serotype A, and to a lesser extent serotype B are used for medical treatment. The effect of BTX is based on its temporary inhibition of cholinergic neurotransmission. Commercially available preparations (BTX-A: BOTOX und Dysport; BTX-B: NeuroBloc) have specific characteristics in children. They are not schematically interchangeable and their safe and effective use requires special training. The introduction of BTX constitutes a major evidence-based and internationally confirmed advance in the treatment of cerebral palsy (CP). This treatment option should be considered and competently discussed for each child with CP as part of an interdisciplinary therapeutic concept that is adapted to each child’s individual stage of motor development. BTX for children is considered in paediatric neurology, rehabilitation, neurology, orthopaedics and in sociopaediatric centres. In dialogue between these disciplines it should be possible to further develop the range of indications for BTX in children and to standardise the sequence of procedures