To date, there are no age-appropriate instruments for assessing the subjective impact of pediatric traumatic brain injury (TBI) sequelae on multiple domains of health-related quality of life (HRQoL) in young children. The present study therefore aims to develop and examine the psychometric properties of a new disease-specific, self-reported HRQoL instrument, the Quality of Life after Brain Injury for children aged 6–7 years (QOLIBRI-KIDDY). Questionnaire development included focus group interviews, cognitive debriefings, and Delphi expert panels. The pilot version of the instrument was tested in 72 children (6.00–7.92 years of age; 60% boys; 86% after mild TBI). After item reduction based on a confirmatory scale analysis considering the six-factor structure of the questionnaire versions for older children, adolescents, and adults (Cognition, Self, Daily Life & Autonomy, Social Relationships, Emotions, Physical Problems), its reliability and validity were investigated. The final version of the QOLIBRI-KIDDY comprises 23 items. Psychometric analyses indicated internal consistency to be satisfactory ( ɑ = 0.49–0.72; ω = 0.57–0.78). Construct validity suggested the expected overlap between generic HRQoL and TBI-specific HRQoL ( r = 0.17–0.36). There were small ( r > 0.2) to moderate ( r > 0.3) correlations between lower TBI-specific HRQoL and participants with lower learning rates, anxiety, depression, and post-concussion symptoms, particularly on the Cognition, Social Relationships, Emotions, and Physical Problems scales. The comparison of known groups revealed significant moderate and significant effects for lower HRQoL in children with depressive symptoms on the Emotions scale ( d = − 0.46) and with post-concussion symptoms on the Cognition ( d = − 0.42) and Social Relationships scales ( d = − 0.56). The QOLIBRI-KIDDY is a comprehensive, yet economical tool, comparable in content and items to the other age-adapted QOLIBRI versions. Its application has the potential to provide longitudinal data on subjects after TBI from childhood to older age, with a subjective perspective that can contribute to improving the therapy, rehabilitation, and daily life of young children.

BACKGROUND:The QOLIBRI-KID/ADO-Proxy is the first disease-specific health-related quality of life (HRQoL) proxy questionnaire developed for use in the field of pediatric traumatic brain injury (TBI), when children are unable to report their HRQoL themselves. METHODS:Its psychometric properties in a German-speaking context are examined in two samples (development and validation). Dyads of 600 parents and their children (aged 8-17 years) were included. RESULTS:The 35-item questionnaire covers six dimensions (Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, and Physical Problems). Results showed good to excellent internal consistencies, acceptable test-retest reliability, and low to fair parent-child agreement. Confirmatory factor analyses supported the one-level six-factor structure. In terms of construct validity, there was an overlap between the disease-specific and the generic HRQoL. Lower parent-reported HRQoL in children was associated with lower parental education, lower functional recovery (Study I), more recent TBI, and more severe depressive, anxiety, and post-concussion symptoms. Findings differed between the two studies in terms of age, gender, and TBI severity. Study I found more severe TBI linked to lower HRQoL in adolescents, while Study II indicated lower HRQoL ratings in girls. CONCLUSION:The QOLIBRI-KID/ADO-Proxy is recommended when individuals are unable to self-report their HRQoL.

Abstract Background The German Rivermead Post-Concussion Symptoms Questionnaire (RPQ) can be used to assess post-concussion symptoms (PCS) after traumatic brain injury (TBI) in adults, adolescents, and children. Methods In this study, we examined the psychometric properties of the German RPQ proxy version (N = 146) for children (8—12 years) after TBI at the item, total and scale score level. Construct validity was analyzed using rank correlations with the proxy-assessed Post-Concussion Symptoms Inventory (PCSI-P), the Patient Health Questionnaire 9 (PHQ-9), and the Generalized Anxiety Disorder Scale 7 (GAD-7). Furthermore, sensitivity testing was performed concerning subjects’ sociodemographic and injury-related characteristics. Differential item functioning (DIF) was analyzed to assess the comparability of RPQ proxy ratings for children with those for adolescents. Results Good internal consistency was demonstrated regarding Cronbach’s α (0.81—0.90) and McDonald’s ω (0.84—0.92). The factorial validity of a three-factor model was superior to the original one-factor model. Proxy ratings of the RPQ total and scale scores were strongly correlated with the PCSI-P (ϱ = 0.50—0.69), as well as moderately to strongly correlated with the PHQ-9 (ϱ = 0.49—0.65) and the GAD-7 (ϱ = 0.44—0.64). The DIF analysis revealed no relevant differences between the child and adolescent proxy versions. Conclusions The German RPQ proxy is a psychometrically reliable and valid instrument for assessing PCS in children after TBI. Therefore, RPQ self- and proxy-ratings can be used to assess PCS in childhood as well as along the lifespan of an individual after TBI.

Background: The ATTeST study (NCT02770807), conducted in 22 centers on five continents, was a randomized, double-blind, placebo-controlled phase 3 clinical trial of safety and efficacy of two dose levels of intra-erythrocyte dexamethasone sodium phosphate (EryDex) compared to placebo, on neurological symptoms of children with ataxia-telangiectasia (A-T).Methods: The primary efficacy endpoint was change in neurological symptoms from baseline to month 6, measured by modified International Cooperative Ataxia Rating Scale (mICARS) and compared between EryDex and the placebo control using a mixed model repeated measures (MMRM) analysis. The point estimate of treatment effect (least square mean [LSM]) and a p-value are presented.Results: Between March 2nd, 2017 and May 13th, 2021, 175 participants were randomized and received at least one dose of drug: 59 low dose (LD), 57 high dose (HD), and 59 placebo, comprising the intention to treat (ITT) population. Modified ITT (mITT) population comprised 164 participants who received ≥1 dose of drug and had ≥1 efficacy assessments. Per protocol (PP) population comprised 107 participants who missed ≤1 dose of treatment. In the mITT population, mICARS LSM scores were -1·37 (p=0·0847) and -1·40 (p=0·0765), and in PP population LSM scores were -2·80 (p=0·0037) and -2·21 (p=0·0193) for LD and HD group, compared to placebo. For 6 to 9-year-olds in mITT population, LSM scores were -1·35 (p=0·2392) and -2·79 (p=0·0185) for LD and HD; and in PP population, LSM scores were -3·59 (p=0·0071) and -4·39 (p=0·0016) for LD and HD group, compared to placebo. Safety data are presented descriptively.Conclusions: At 6-month follow-up HD EryDex was effective in reducing mICARS scores in 6 to 9-year-olds. Both LD and HD EryDex were effective when used without skipping treatments and as outlined in the protocol. There were no safety concerns identified. Further studies of HD EryDex in the 6 to 9-year group are under way.Trial Registration: NCT02770807.Funding: EryDel S.p.A., Quince Therapeutics.Declaration of Interest: Declares “none” for interests: A.V., B.P., M.R., R.B., S.I.P., S.G., S.W., S.P., V.L., D.T., A.H., A.N. declares being a part of consortium which obtained Horizon 2020 grant for this project. A.S-P. declares funds, equipment and drug from EryDel received for this trial; grants for research in A-T (AT children’s project, AEFAT, Action for AT, Klinbeforsk, and Dam Foundation); and being the President of Norwegian Society for Medical Genetics. E.F. declares receiving support from EryDel for this project. G.J. declares being employed as a Chief Medical Officer by the study sponsor; he was medical monitor for this trial, and received stock options. I.M. declares receiving consulting fees/honoraria/travel support from Boehringer-Ingelheim, Takeda and CSL-Behring, for work unrelated to this project. She declares holding unpaid leadership positions in the past (president for ESID Society, MAB IPOPI). K.V. declares getting honoraria from MedLink Neurology and holding leadership positions (Secretary General, Indian Epilepsy Society and Asian Epilepsy Academy). L.B. declares holding a leadership role in Newron Pharmaceuticals and receiving stock options from Quince Therapeutics. MK.K. declares funding to her institution from EryDel for this trial; receiving funding from Quince Therapeutics for expanded access program; and getting travel support for the investigator meeting. M.M. declares receiving a grant/contract and travel support from EryDel; leadership position with Diatheva SrL; and holding EryDel and Quince Therapeutics stocks. P.P. declares EryDel’s research support for this trial, paid to his institution; research grants from ICMR, DST, SERB, DBT, Welcome-DBP, PACE, SKAN and MJF all paid to his institution; honoraria as faculty/speaker/author or travel/meeting registration support from the International Parkinson and Movement Disorder Society, Movement Disorders Societies of Korea, Taiwan and Bangladesh, and National Institute of Mental Health and Neurosciences; leadership positions include Chair of Education Committee of IPMDS, and unpaid Editor-in-Chief of Annals of Movement Disorders. R.Y. declares research grants from Indian Council of Medical Research (ICMR), Parkinson’s and Movement Disorders Research Fund of NIMHANS, SKAN foundation; book royalties from Jaypee Publisher; speaker honoraria from International Parkison’s and Movement Disorders Society; and leadership role in Parkinson’s Society of Karnataka. R.G. declares participation in data safety monitoring or advisory boards of: Biogen, Hikma, Merck, Roche, and Sanofi. T.C. declares consulting fees from Syneos Health Communications and Scholar Rock; honoraria for CME educational program development/review from MedForce and Muscular Dystrophy Association; and participation on safety monitoring or advisory boards for Taysha Giant Axonal Neuropathy. W.W. declares research funding from EryDel to the institution for this trial; being a member of a data safety monitoring board for clinical trial of an IMP in A-T; and being trustee of charity STARS. H.L. declares research funding and equipment from EryDel to the institution for this trial; consulting fees from EryDel for analysis of adverse events and presentation to the FDA, travel support for attending investigator meetings for this trial. V.U. declares research funding from EryDel to his institution for this trial. S.Z. declares that the Frankfurt University was funded by the Horizon grant of the EU and EryDel for conducting this trial; research grants outside submitted work (Palas GmbH Company Karlsruhe Germany “Aerosol measurement” and a grant from Ministry of Health of the German Republic (BMBF) for the study of Tiotropium in asthma 1-5 years); consulting fees or honoraria from Engelhard GmbH, Bӧhringer Ingelheim, Allergy Therapeutics, AstraZeneca, Sanofi Aventis, EryDel SpA, and Lofarma; member of EAACI Guidelines group on allergic asthma. M.K. declares funding from EryDel for this trial and funding from Quince Therapeutics for the expanded access program; consulting fees from Desitin Pharma, Eisai Pharma, STADApharm, and Life Science Consulting; travel support from Desitin Pharma; participation on a data safety monitoring board for Eisai Pharma; being on the Board and being a Vice President for Neuropaediatric Society (Germany, Austria, Switzerland).Ethical Approval: The trial was conducted in accordance with the Good Clinical Practice guidelines of the International Conference on Harmonization (ICH) and the ethical principles of the Declaration of Helsinki. Written informed consent/parental permission was obtained from all participants and/or parents or legal guardians, before screening. An independent data and safety monitoring board reviewed the safety data throughout the trial. The protocol, approved by regulatory authorities and ethics committees of all participating study sites.

Until recently, no disease-specific health-related quality of life (HRQoL) questionnaire existed for pediatric traumatic brain injuries (TBIs). In this revalidation study, the psychometric properties and the validity of the 35-item QOLIBRI-KID/ADO questionnaire in its final German version were examined in 300 children and adolescents. It is the first self-reported TBI-specific tool for measuring pediatric HRQoL in individuals aged between 8 and 17 years. The six-factor model fits the data adequately. The questionnaire's internal consistency was excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability, and the measure's construct validity was supported by the overlap between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. The discriminant validity tests showed that older children and girls reported a significantly lower HRQoL than comparison groups, and this was also true of children who were anxious or depressed, or who suffered from post-concussion symptoms, replicating the results of the questionnaire's first developmental study. Our results suggest that the QOLIBRI-KID/ADO is a reliable and valid multidimensional tool that can be used together with the adult version in clinical contexts and research to measure disease-specific HRQoL after pediatric TBI throughout a person's life. This may help improve care, treatment, daily functioning, and HRQoL after TBI.

Foramina parietalia permagna (FPP) is a rare anatomical defect that affects the parietal bones of the human skull. FPP is characterized by symmetric perforations on either side of the skull, which are caused by insufficient ossification during embryogenesis. These openings are typically abnormally large and can range from a few millimeters to several centimeters in diameter. Enlarged foramina are often discovered incidentally during anatomical or radiological examinations and in most cases left untreated unless symptoms develop. Although this calvarial defect is usually asymptomatic, it may be accompanied by neurological or vascular conditions that can have clinical significance in certain cases. FPP is an inherited disorder and arises due to mutations in either Msh homeobox 2 (MSX2) or aristaless-like homeobox 4 (ALX4) genes. In almost all cases, one parent is affected. Clinical findings and diagnostic imaging typically contribute to determine the diagnosis.

BACKGROUND:Ataxia telangiectasia is a multisystem disorder with progressive neurodegeneration. Corticosteroids can improve neurological functioning in patients with the disorder but adrenal suppression and symptom recurrence on treatment discontinuation has limited their use, prompting the development of novel steroid delivery systems. The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in children with ataxia telangiectasia. METHODS:This multicentre, randomised, double-blind, placebo-controlled, phase 3 trial was done at 22 centres in 12 countries (Australia, Belgium, Germany, India, Israel, Italy, Norway, Poland, Spain, Tunisia, the UK, and the USA). Eligible participants were children aged 6 years or older weighing more than 15 kg who met clinical criteria for ataxia telangiectasia but who had preserved autonomous gait. Participants were randomly assigned (1:1:1) to low-dose (approximately 5-10 mg), or high-dose (approximately 14-22 mg) intra-erythrocyte dexamethasone sodium phosphate, or placebo, using an independent interactive web response system, with minimisation for sex and age (6-9 years vs ≥10 years). Intravenous intra-erythrocyte dexamethasone sodium phosphate was administered once a month for 6 months. Participants, employees of the sponsor, investigators, all raters of efficacy endpoints, and central reviewers were masked to treatment assignment and dose allocations. The primary efficacy endpoint was change in the modified International Cooperative Ataxia Rating Scale (mICARS) from baseline to month 6, assessed in the modified intention-to-treat (mITT) population, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline efficacy assessment. This trial is registered with Clinicaltrials.gov (NCT02770807) and is complete. FINDINGS:Between March 2, 2017, and May 13, 2021, 239 children were assessed for eligibility, of whom 176 were randomly assigned. One patient assigned to high-dose intra-erythrocyte dexamethasone sodium phosphate did not initiate treatment. 175 patients received at least one dose of treatment (59 patients received the low dose and 57 received the high dose of intra-erythrocyte dexamethasone sodium phosphate, and 59 received placebo). The mITT population comprised 164 participants (56 children in the low-dose group, 54 children in the high-dose group, and 54 in the placebo group). Compared with the placebo group, no differences were identified with regard to change in mICARS score from baseline to 6 months in the low-dose group (least squares mean difference -1·37 [95% CI -2·932 to 0·190]) or the high-dose group (-1·40 [-2·957 to 0·152]; p=0·0765). Adverse events were reported in 43 (73%) of 59 participants in the low-dose group, 47 (82%) of 57 participants in the high-dose group, and 43 (73%) of 59 participants in the placebo group. Serious adverse events were observed in six (10%) of 59 participants in the low-dose group, seven (12%) of 57 participants in the high-dose group, and seven (12%) of 59 participants in the placebo group. There were no reports of hyperglycaemia, hypertension, hirsutism, or Cushingoid appearance in any of the treatment groups, nor any treatment-related deaths. INTERPRETATION:Although there were no safety concerns, the primary efficacy endpoint was not met, possibly related to delays in treatment reducing the number of participants who received treatment as outlined in the protocol, and potentially different treatment effects according to age. Studies of intra-erythrocyte delivery of dexamethasone sodium phosphate will continue in participants aged 6-9 years, on the basis of findings from subgroup analyses from this trial. FUNDING:EryDel and Quince Therapeutics.

The impact of pediatric traumatic brain injury (pTBI) on health-related quality of life (HRQoL) in children and adolescents remains understudied. Short scales have some advantages in terms of economy and administration over longer scales, especially in younger children. The aim of the present study is to psychometrically evaluate the six-item German version of the QOLIBRI-OS-KID/ADO scale for children and adolescents. In addition, reference values from a general German pediatric population are obtained to assist clinicians and researchers in the interpretation of HRQoL after pTBI. A total of 297 individuals after TBI and 1997 from a general population sample completed the questionnaire. Reliability, validity, and comparability of the assessed construct were examined. The questionnaire showed satisfactory reliability (α = 0.75 and ω = 0.81 and α = 0.85 and ω = 0.86 for the TBI and general population samples, respectively). The QOLIBRI-OS-KID/ADO was highly correlated with its long version (R2 = 67

In the field of pediatric traumatic brain injury (TBI), relationships between pre-injury and injury-related characteristics and post-TBI outcomes (functional recovery, post-concussion depression, anxiety) and their impact on disease-specific health-related quality of life (HRQoL) are under-investigated. Here, a multidimensional conceptual model was tested using a structural equation model (SEM). The final SEM evaluates the associations between these four latent variables. We retrospectively investigated 152 children (8-12 years) and 148 adolescents (13-17 years) after TBI at the recruiting clinics or online. The final SEM displayed a fair goodness-of-fit (SRMR = 0.09, RMSEA = 0.08 with 90% CI [0.068, 0.085], GFI = 0.87, CFI = 0.83), explaining 39% of the variance across the four latent variables and 45% of the variance in HRQoL in particular. The relationships between pre-injury and post-injury outcomes and between post-injury outcomes and TBI-specific HRQoL were moderately strong. Especially, pre-injury characteristics (children's age, sensory, cognitive, or physical impairments, neurological and chronic diseases, and parental education) may aggravate post-injury outcomes, which in turn may influence TBI-specific HRQoL negatively. Thus, the SEM comprises potential risk factors for developing negative post-injury outcomes, impacting TBI-specific HRQoL. Our findings may assist healthcare providers and parents in the management, therapy, rehabilitation, and care of pediatric individuals after TBI.

The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) assesses post-concussion symptoms (PCS) after traumatic brain injury (TBI). The current study examines the applicability of self-report and proxy versions of the German RPQ in adolescents (13–17 years) after TBI. We investigated reliability and validity on the total and scale score level. Construct validity was investigated by correlations with the Post-Concussion Symptoms Inventory (PCSI-SR13), Generalized Anxiety Disorder Scale 7 (GAD-7), and Patient Health Questionnaire 9 (PHQ-9) and by hypothesis testing regarding individuals’ characteristics. Intraclass correlation coefficients (ICC) assessed adolescent–proxy agreement. In total, 148 adolescents after TBI and 147 proxies completed the RPQ. Cronbach’s α (0.81–0.91) and McDonald’s ω (0.84–0.95) indicated good internal consistency. The three-factor structure outperformed the unidimensional model. The RPQ was strongly correlated with the PCSI-SR13 (self-report: r = 0.80; proxy: r = 0.75) and moderately–strongly with GAD-7 and PHQ-9 (self-report: r = 0.36, r = 0.35; proxy: r = 0.53, r = 0.62). Adolescent–proxy agreement was fair (ICC [2,1] = 0.44, CI95% [0.41, 0.47]). Overall, both self-report and proxy assessment forms of the German RPQ are suitable for application in adolescents after TBI. As proxy ratings tend to underestimate PCS, self-reports are preferable for evaluations. Only if a patient is unable to answer, a proxy should be used as a surrogate.

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.

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.

Previous studies have found facial emotion recognition (FER) impairments in individuals with epilepsy. While such deficits have been extensively explored in individuals with focal temporal lobe epilepsy, studies on individuals with generalized epilepsies are rare. However, studying FER specifically in individuals with juvenile myoclonic epilepsy (JME) is particularly interesting since they frequently suffer from social and neuropsychological difficulties in addition to epilepsy-specific symptoms. Furthermore, recent brain imaging studies have shown subtle microstructural alterations in individuals with JME. FER is considered a fundamental social skill that relies on a distributed neural network, which could be disturbed by network dysfunction in individuals with JME. This cross-sectional study aimed to examine FER and social adjustment in individuals with JME. It included 27 patients with JME and 27 healthy controls. All subjects underwent an Ekman-60 Faces Task to examine FER and neuropsychological tests to assess social adjustment as well as executive functions, intelligence, depression, and personality traits. Individuals with JME performed worse in global FER and fear and surprise recognition than healthy controls. However, probably due to the small sample size, no significant difference was found between the two groups. A potential FER impairment needs to be confirmed in further studies with larger sample size. If so, patients with JME could benefit from addressing possible deficits in FER and social difficulties when treated. By developing therapeutic strategies to improve FER, patients could be specifically supported with the aim of improving social outcomes and quality of life.

BACKGROUND AND PURPOSE:Ataxia-telangiectasia (A-T) is a rare, autosomal recessive, multisystem disorder that leads to progressive neurodegeneration with cerebellar ataxia and peripheral polyneuropathy. Cerebellar neurodegeneration is well described in A-T. However, peripheral nervous system involvement is an underdiagnosed but important additional target for supportive and systemic therapies. The aim of this study was to conduct neurophysiological measurements to assess peripheral neurodegeneration and the development of age-dependent neuropathy in A-T.METHODS:In this prospective study, 42 classical A-T patients were assessed. The motor and sensory nerve conduction of the median and tibial nerves was evaluated. Data were compared to published standard values and a healthy age- and gender-matched control group of 23 participants. Ataxia scores (Klockgether, Scale for the Assessment and Rating of Ataxia) were also assessed.RESULTS:In A-T, neurophysiological assessment revealed neuropathic changes as early as the first year of life. Subjective symptomatology of neuropathy is rarely described. In the upper extremities, motor neuropathy was predominantly that of a demyelinating type and sensory neuropathy was predominantly that of a mixed type. In the lower extremities, motor and sensory neuropathy was predominantly that of a mixed type. We found significant correlations between age and the development of motor and sensory polyneuropathy in A-T compared with healthy controls (p < 0.001).CONCLUSIONS:In A-T, polyneuropathy occurs mostly subclinically as early as the first year of life. The current study of a large national A-T cohort demonstrates that development of neuropathy in A-T differs in the upper and lower extremities.

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials. The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly. This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5

OBJECTIVE:The aim was to investigate the monitoring, interventions, and occurrence of critical, potentially life-threatening incidents in patients with Dravet syndrome (DS) and caregivers' knowledge about sudden unexpected death in epilepsy (SUDEP). METHODS:This multicenter, cross-sectional study of patients with DS and their caregivers in Germany consisted of a questionnaire and prospective diary querying the disease characteristics and demographic data of patients and caregivers. RESULTS:Our analysis included 108 questionnaires and 82 diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 (SD ± 10.0 years) and primary caregivers were 92.6% (n = 100) female, with a mean age of 44.7 (SD ± 10.6 years). Monitoring devices were used regularly by 75.9% (n = 82) of caregivers, and most monitored daily/nightly. Frequently used devices were pulse oximeters (64.6%), baby monitors (64.6%), thermometers (24.1%), and Epi-Care (26.8%). Younger caregiver and patient age and history of status epilepticus were associated with increased use of monitoring, and 81% of monitor users reported having avoided a critical incident with nocturnal monitoring. The need for resuscitation due to cardiac or respiratory arrest was reported by 22 caregivers (20.4%), and most cases (72.7%) were associated with a seizure. Caregivers reported frequently performing interventions at night, including oropharyngeal suction, oxygenation, personal hygiene, and change of body position. Most caregivers were well informed about SUDEP (n = 102; 94%) and monitored for a lateral or supine body position; however, only 39.8% reported receiving resuscitation training, whereas 52.8% (n = 57) knew what to do in case the child's breathing or heart activity failed. SIGNIFICANCE:Critical incidents and the need for resuscitation are reported frequently by caregivers and may be related to high mortality and SUDEP rates in DS. Resuscitation training is welcomed by caregivers and should be continuously provided. Oxygen monitoring devices are frequently used and considered useful by caregivers.

BackgroundPost-concussion symptoms (PCS) are a common consequence of pediatric traumatic brain injury (pTBI). They include cognitive, emotional, and physical disturbances. To address the lack of age-adapted instruments assessing PCS after pTBI, this study examines the psychometric properties of the German 17-item post-TBI version of the Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8–12 years. The study also aims to establish reference values based on data from a pediatric general population sample to better estimate the prevalence and clinical relevance of PCS after pTBI in clinical and research settings.MethodsA total of 132 children aged 8–12 years from a post-acute TBI sample and 1,047 from a general population sample were included in the analyses. The questionnaire was translated from English into German and linguistically validated using forward and backward translation and cognitive debriefing to ensure comprehensibility of the developed version. Reliability and validity were examined; descriptive comparisons were made with the results of the English study. Measurement invariance (MI) analyses between TBI and general population samples were conducted prior to establishing reference values. Factors contributing to the total and scale scores of the PCSI-SR8 were identified using regression analyses. Reference values were calculated using percentiles.ResultsMost children (TBI: 83%; general population: 79%) rated at least one symptom as “a little” bothersome. The German PCSI-SR8 met the psychometric assumptions in both samples and was comparable to the English version. The four-factor structure comprising physical, emotional, cognitive, and fatigue symptoms could be replicated. The MI assumption was retained. Therefore, reference values could be provided to determine the symptom burden of patients in relation to a comparable general population. Clinical relevance of reported symptoms is indicated by a score of 8, which is one standard deviation above the mean of the general population sample.ConclusionThe German version of the PCSI-SR8 is suitable for assessment of PCS after pTBI. The reference values allow for a more comprehensive evaluation of PCS following pTBI. Future research should focus on validation of the PCSI-SR8 in more acute phases of TBI, psychometric examination of the pre-post version, and child-proxy comparisons.