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

Deep Brain Stimulation in KMT2B-Related Dystonia: Case Report and Review of the Literature With Special Emphasis on Dysarthria and Speech

Objective: KMT2B-related dystonia is a progressive childhood-onset movement disorder, evolving from lower-limb focal dystonia into generalized dystonia. With increasing age, children frequently show prominent laryngeal or facial dystonia manifesting in dysarthria. Bilateral deep brain stimulation of the globus pallidus internus (GPi-DBS) is reported to be an efficient therapeutic option. Especially improvement of dystonia and regaining of independent mobility is commonly described, but detailed information about the impact of GPi-DBS on dysarthria and speech is scarce. Methods: We report the 16-months outcome after bilateral GPi-DBS in an 8-year-old child with KMT2B-related dystonia caused by a de-novo c.3043C>T (p.Arg1015*) non-sense variant with special emphasis on dysarthria and speech. We compare the outcome of our patient with 59 patients identified through a PubMed literature search. Results: A remarkable improvement of voice, articulation, respiration and prosodic characteristics was seen 16 months after GPi-DBS. The patients' speech intelligibility improved. His speech became much more comprehensible not only for his parents, but also for others. Furthermore, his vocabulary and the possibility to express his feelings and wants expanded considerably. Conclusion: A positive outcome of GPi-DBS on speech and dysarthria is rarely described in the literature. This might be due to disease progression, non-effectiveness of DBS or due to inadvertent spreading of the electrical current to the corticobulbar tract causing stimulation induced dysarthria. This highlights the importance of optimal lead placement, the possibility of horizontal steering of the electrical field by applying directional stimulation with segmented leads as well as the use of the lowest possible effective stimulation intensity

Childhood Stroke: Awareness, Interest, and Knowledge Among the Pediatric Community

Objective: Acute childhood stroke is an emergency requiring a high level of awareness among first-line healthcare providers. This survey serves as an indicator of the awareness of, the interest in, and knowledge of childhood stroke of German pediatricians.Methods: Thousand six hundred and ninety-seven physicians of pediatric in- and outpatient facilities in Bavaria, Germany, were invited via email to an online-survey about childhood stroke.Results: The overall participation rate was 14%. Forty-six percent of participants considered a diagnosis of childhood stroke at least once during the past year, and 47% provide care for patients who have suffered childhood stroke. The acronym FAST (Face-Arm-Speech-Time-Test) was correctly cited in 27% of the questionnaires. Most commonly quoted symptoms of childhood stroke were hemiparesis (90%), speech disorder (58%), seizure (44%), headache (40%), and impaired consciousness (33%). Migraine (63%), seizure (39%), and infections of the brain (31%) were most frequently named as stroke mimics. Main diagnostic measures indicated were magnetic resonance imaging (MRI) (96%) and computer tomography (CT) (55%). Main therapeutic strategies were thrombolysis (80%), anticoagulation (41%), neuroprotective measures, and thrombectomies (15% each). Thirty-nine percent of participants had taken part in training sessions, 61% studied literature, 37% discussed with colleagues, and 25% performed internet research on childhood stroke. Ninety-three percent of participants approve skill enhancement, favoring training sessions (80%), publications (43%), and web based offers (35%). Consent for offering a flyer on the topic to caregivers in facilities was given in 49%.Conclusion: Childhood stroke constitutes a topic of clinical importance to pediatricians. Participants demonstrate a considerable level of comprehension concerning the subject, but room for improvement remains. A multi-modal approach encompassing an elaborate training program, regular educational publications in professional journals, and web based offers could reach a broad range of health care providers. Paired with a public adult and childhood stroke awareness campaign, these efforts could contribute to optimize the care for children suffering from stroke

Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1

Background: Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin. Methods: In NF1 patients (n = 11; 19-44 years) and healthy controls (HC; n = 11; 19-31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed. Results: In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness. Conclusions: This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option

Quality of life after brain injury in children and adolescents (QOLIBRI-KID/ADO)-The first disease-specific self-report questionnaire after traumatic brain injury

The subjective impact of the consequences of pediatric traumatic brain injury (pTBI) on different life dimensions should be assessed multidimensionally and as sensitively as possible using a disease-specific health-related quality of life (HRQoL) instrument. The development and psychometrics of the first such self-report questionnaire for children and adolescents after TBI are reported here. Focus group interviews with children, adolescents, and their parents, cognitive debriefing, item pool generation and reduction using Delphi expert panels were performed. The resulting version was psychometrically tested on 300 individuals aged 8–17 years. After item reduction based on factor analyses, differential item functioning, reliability, and validity were investigated. The final 35 items were associated with six scales (Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, Physical Problems). Internal consistency and construct validity were satisfactory. Health-related Quality of life (HRQoL) was significantly lower in older and in female participants, as well as those with cognitive disabilities, anxiety, depression and post-concussion symptoms, than in comparative groups. The new QOLIBRI-KID/ADO is a comprehensive, multidimensional, reliable, and valid instrument, comparable in content and items to the QOLIBRI adult version. Therefore, disease-specific HRQoL can now be measured across the lifespan and may support the amelioration of treatment, care, rehabilitation, and daily life of children and adolescents after TBI.This research was funded by Dr. Senckenbergische Stiftung/Clementine Kinderhospital Dr. Christ‘sche Stiftungen (Germany), and Uniscientia Stiftung (Switzerland)

Advanced Robotic Therapy Integrated Centers (ARTIC): an international collaboration facilitating the application of rehabilitation technologies

Background: The application of rehabilitation robots has grown during the last decade. While meta-analyses have shown beneficial effects of robotic interventions for some patient groups, the evidence is less in others. We established the Advanced Robotic Therapy Integrated Centers (ARTIC) network with the goal of advancing the science and clinical practice of rehabilitation robotics. The investigators hope to exploit variations in practice to learn about current clinical application and outcomes. The aim of this paper is to introduce the ARTIC network to the clinical and research community, present the initial data set and its characteristics and compare the outcome data collected so far with data from prior studies. Methods: ARTIC is a pragmatic observational study of clinical care. The database includes patients with various neurological and gait deficits who used the driven gait orthosis Lokomat® as part of their treatment. Patient characteristics, diagnosis-specific information, and indicators of impairment severity are collected. Core clinical assessments include the 10-Meter Walk Test and the Goal Attainment Scaling. Data from each Lokomat® training session are automatically collected. Results: At time of analysis, the database contained data collected from 595 patients (cerebral palsy: n = 208; stroke: n = 129; spinal cord injury: n = 93; traumatic brain injury: n = 39; and various other diagnoses: n = 126). At onset, average walking speeds were slow. The training intensity increased from the first to the final therapy session and most patients achieved their goals. Conclusions: The characteristics of the patients matched epidemiological data for the target populations. When patient characteristics differed from epidemiological data, this was mainly due to the selection criteria used to assess eligibility for Lokomat® training. While patients included in randomized controlled interventional trials have to fulfill many inclusion and exclusion criteria, the only selection criteria applying to patients in the ARTIC database are those required for use of the Lokomat®. We suggest that the ARTIC network offers an opportunity to investigate the clinical application and effectiveness of rehabilitation technologies for various diagnoses. Due to the standardization of assessments and the use of a common technology, this network could serve as a basis for researchers interested in specific interventional studies expanding beyond the Lokomat®

Therapy of Sialorrhea with Botulinum Toxin - An Update

Jost WH, Baumer T, Berweck S, et al. Therapie der Sialorrhoe mit Botulinumtoxin – ein Update. Fortschritte der Neurologie-Psychiatrie. 2022.The most important salivary glands are the paired parotid and submandibular glands. Adults produce 1 to 1.5liters of saliva which are then regularly swallowed. When the act of swallowing is disturbed, salivation occurs. More rarely, the cause can be found in increased saliva production, for example, when caused through medication. Sialorrhea impairs the quality of life substantially and is frequently often socially stigmatizing. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, as well as, in selected cases, radiation and surgical measures. Over the last 20 years, local injection of botulinum toxin has been successfully applied in the treatment of this condition. With approval of incobotulinumtoxinA toxin for children and adults, this procedure will become the therapy of choice for chronic sialorrhea. The results of the phase III registration trials have demonstrated high efficacy and good safety of the injection treatment in both children and adults. Thieme. All rights reserved

Placebo-controlled clinical trial of incobotulinumtoxinA for sialorrhea in children : sIPEXI

BACKGROUND AND OBJECTIVES: To investigate the efficacy and safety of repeated injections of incobotulinumtoxinA (incoBoNT/A) for treatment of chronic sialorrhea (drooling) associated with neurologic disorders (e.g., cerebral palsy, traumatic brain injury) or intellectual disability in children and adolescents in a prospective phase III study (SIPEXI [Sialorrhea Pediatric Xeomin Investigation]). METHODS: The study enrolled 2- to 17-year-old patients with sialorrhea due to neurologic disorders or intellectual disability. Patients received body weight–dependent doses of incoBoNT/A (20–75 U). A main period with 1 injection cycle (placebo-controlled, double-blind, 6- to 17-year-olds) was followed by an open-label extension with up to 3 further cycles. An additional cohort of 2- to 5-year-olds received active treatment throughout the study. Coprimary endpoints were the change in unstimulated salivary flow rate (uSFR) from baseline to week 4 and the carers' Global Impression of Change Scale (GICS) rating at week 4. Adverse events were recorded. RESULTS: In the main period, 220 patients aged 6–17 years were randomized and treated (148 patients in incoBoNT/A group, 72 patients in placebo group). A total of 35 patients aged 2–5 years received incoBoNT/A (no placebo). A total of 214 patients aged 6–17 years and 33 patients aged 2–5 years continued treatment in the open-label extension period. For the 6- to 17-year-olds, a significant difference between incoBoNT/A and placebo was seen in mean uSFR decrease (difference −0.06 g/min; p = 0.0012) and the carers' GICS rating (difference 0.28 points; p = 0.032) at week 4, in favor of active treatment. The secondary endpoints consistently supported these results. A sustained benefit was observed during the extension. Incidences of adverse events were comparable between incoBoNT/A and placebo and did not increase notably with repeated injections. The most common adverse events were respiratory infections. Efficacy and safety were also favorable in the uncontrolled cohort of 2- to 5-year-olds. DISCUSSION: Both co–primary efficacy endpoints were reached and superiority of incoBoNT/A over placebo was confirmed. IncoBoNT/A (up to 75 U, up to 4 cycles) is an effective and well-tolerated treatment for sialorrhea associated with neurologic disorders in children. TRIAL REGISTRATION INFORMATION: Clinicaltrials.gov: NCT02270736 (clinicaltrials.gov/ct2/show/results/NCT02270736); EU Clinical Trials Register: 2013-004532-30 (clinicaltrialsregister.eu/ctr-search/search?query=2013-004532-30). CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that injection of incobotulinumtoxinA decreases drooling in children aged 6 to 17 years with neurologic disorders