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The association of recognisable neurological conditions with an underlying malignancy is well described. In this review we explore the complex interplay of genetic, environmental and tumour factors which contribute to autoimmunity and paraneoplastic conditions. We review the current understanding of the pathogenesis of well recognised paraneoplastic conditions in children including Opsoclonus myoclonus ataxia syndrome, N-Methyl-D Aspartate receptor encephalitis and limbic encephalitis, and the broad approaches to treatment. Rapid advances in oncological treatment has expanded the arsenal of therapeutic modalities. We explore the broad spectrum of immune therapies in childhood cancer, and the potential neurological complications of these novel therapies, and discuss the fine balance of risk and benefit that these bring. • Sex, age, ethnicity, genetic vulnerability and malignancy are factors associated with brain directed autoimmunity. • In OMAS NMDARE immune and oncological management are required for optimal management of these rare childhood conditions. • Immunotherapy in the treatment of childhood cancers has potential to improve both survival and quality of life. • Immune check-point inhibitors are associated with neurological immune-related adverse events in at least 10 % of patients. [ABSTRACT FROM AUTHOR]

Resumen: Introducción: En los últimos años se han producido importantes cambios en la prevención y tratamiento del ictus isquémico agudo en el adulto. Sin embargo, la baja incidencia en edades pediátricas hace más difícil desarrollar protocolos y guías de asistencia específicas. Este trabajo busca conocer la situación de estos niños en nuestra región, con el objetivo de establecer un protocolo autonómico que mejore la atención a estos pacientes. Métodos: Estudio de incidencia de base hospitalaria del ictus infantil (≤15 años de edad) en Aragón (1.308.728 habitantes, 15% ≤15 años), desde 2008 a 2019. Los datos se extrajeron de los episodios de alta hospitalaria, incluidas las defunciones, del Servicio Aragonés de Salud, de acuerdo a los códigos de la Codificación Internacional de Enfermedades (CIE) definidos para enfermedad cerebrovascular. Se analizaron aspectos demográficos, clínicos, diagnóstico-terapéuticos y de pronóstico. Resultados: Se recogieron un total de 21 eventos, ocho isquémicos (38,1%) y 13 hemorrágicos (61,9%). La media de edad fue 9,3 años (desviación típica 1,0). Hubo 12 hombres y nueve mujeres. No se encontraron diferencias estadísticamente significativitas entre ictus isquémicos y hemorrágicos, salvo por el síntoma guía (déficit motor o del lenguaje en isquémicos, y cefalea en hemorrágicos). Ninguno de los eventos isquémicos recibió terapias de reperfusión. Incluyendo los tres pacientes que fallecieron durante el ingreso, ocho (42,1%) tenían una puntuación en la escala modificada de Rankin (mRS) > 2 a los 12 meses. El déficit motor fue la secuela más común (n = 9). Conclusiones: El ictus infantil, aunque infrecuente, supone una importante limitación funcional. En España, Madrid fue pionera en adaptar las redes de asistencia existentes del Código Ictus en el adulto. En el caso de Aragón, esta revisión nos ha permitido trabajar de cerca con los diferentes actores implicados, para poder ofrecer un plan autonómico de atención al ictus isquémico infantil. Sin embargo, registros nacionales prospectivos ayudarían a avanzar en la atención a estos niños. Abstract: Background: Recent years have seen considerable changes in the prevention and treatment of acute ischaemic stroke in adult patients. However, the low incidence of paediatric stroke makes the development of specific guidelines more challenging. This study aims to clarify the situation of these children in our region in order to establish a regional protocol to improve the care provided to these patients. Methods: We performed a regional incidence study of pediatric stroke (≤ 15 years of age) in Aragon, Spain (1 308 728 population, 15% aged ≤ 15 years) between 2008 and 2019. Data were obtained from hospital discharge records, including deaths, from the regional health service of Aragón, according to ICD codes for cerebrovascular disease. We analysed demographic, clinical, diagnostic/therapeutic, and prognostic variables. Results: A total of 21 events were recorded: 8 ischaemic (38.1%) and 13 haemorrhagic strokes (61.9%). The mean age (SD) was 9.3 years (1.0). The sample included 12 boys and nine girls. No statistically significant differences were found between ischaemic and haemorrhagic strokes, except in the chief complaint (language and motor impairment in ischaemic stroke and headache in haemorrhagic stroke). None of the patients with ischaemic stroke received reperfusion therapies. Including the 3 patients who died during hospitalisation, eight patients (42.1%) had modified Rankin Scale scores > 2 at 12 months. Motor deficits were the most common sequela (n = 9). Conclusion: Though infrequent, paediatric stroke has an important functional impact. In Spain, Madrid was the first region to adapt the existing code stroke care networks for adult patients. In Aragon, this review has enabled us to work closely with the different stakeholders to offer a care plan for acute paediatric ischaemic stroke. Nevertheless, prospective national registries would be valuable to continue improving the care provided to these patients.

Inflammation related to influenza virus infection can lead to multiple neurological presentations. Encephalitis is one of them, mostly accompanied by seizures, with different profiles depending on the epidemics and previous medical conditions. All children presenting neurological symptoms and positive for influenza virus RNA detection in a respiratory sample between November 2018 and April 2023, hospitalized in the Department of Paediatric Neurology of Toulouse Children's Hospital, were retrospectively analysed. Among the 1,277 children diagnosed with influenza in our centre, 131 (10.3 %) were hospitalized for neurological features. The year 2020–2021 was marked by zero incidence of positive influenza tests, associated with the COVID-19 pandemic. Among the 131 patients included, 71.6 % were under 5 years old. Most of them (80.9 %) were infected by influenza A virus. The first neurological symptoms were mainly seizures in 73.3 % of patients. Possible or confirmed encephalitis was observed in 29 % of cases, including one acute necrotizing encephalopathy. Few children (6.1 %) presented with acute myositis. Twenty-seven patients (20.6 %) had a personal history of significant previous neurological disorders. Most patients (88.5 %) displayed a rapid favourable outcome, marked by the disappearance of their neurological symptoms within the first 2 days. Anti-epileptic drugs were introduced in 1.5 % of cases, and adapted in 16.8 %, mainly in patients with febrile status epilepticus and an abnormal EEG. Neurological features were frequently associated with influenza infection in children; most were transient. Effects on long-term neurodevelopmental outcomes need to be clarified as our follow-up was limited, especially in children with pre-existing neurological conditions. • Influenza associated neurological manifestations are frequent in children. • Most neurological presentations of influenza are transitory but responsible for a significant number of hospitalisations. • Severe complications of influenza-associated encephalopathy remain rare. • Patients with pre-existing neurological conditions are at greater risk of severe neurological forms of Influenza. [ABSTRACT FROM AUTHOR]

BackgroundWe previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.MethodsUsing a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090).Results490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p

OBJECTIVE: The Bayley Scales of Infant Development (BSID) is the most used diagnostic tool to identify neurodevelopmental disorders in children under age 3 but is challenging to use in low-resource countries. The Ages and Stages Questionnaire (ASQ) is an easy-to-use, low-cost clinical tool completed by parents/caregivers that screens children for developmental delay. The objective was to determine the performance of ASQ as a screening tool for neurodevelopmental impairment when compared with BSID second edition (BSID-II) for the diagnosis of moderate-to-severe neurodevelopmental impairment among infants at 12 and 18 months of age in low-resource countries. METHODS: Study participants were recruited as part of the First Bites Complementary Feeding trial from the Democratic Republic of Congo, Zambia, Guatemala and Pakistan between October 2008 and January 2011. Study participants underwent neurodevelopmental assessment by trained personnel using the ASQ and BSID-II at 12 and 18 months of age. RESULTS: Data on both ASQ and BSID-II assessments of 1034 infants were analysed. Four of five ASQ domains had specificities greater than 90% for severe neurodevelopmental delay at 18 months of age. Sensitivities ranged from 23% to 62%. The correlations between ASQ communications subscale and BSID-II Mental Development Index (MDI) (r=0.38) and between ASQ gross motor subscale and BSID-II Psychomotor Development Index (PDI) (r=0.33) were the strongest correlations found. CONCLUSION: At 18 months, ASQ had high specificity but moderate-to-low sensitivity for BSID-II MDI and/or PDI

ObjectiveTo evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19.DesignLongitudinal cohort study.SettingHospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021.ParticipantsInfants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database.InterventionsGeneral movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6-8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database.Main outcome measuresMotor Optimality Scores Revised (MOS-R) at 3-5 months. Presence of developmental delay (DD) at 6-8 months.Results239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21-24, range 9-28) vs 25 (IQR 24-26, range 20-28) in controls, p

Introduction: Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood‐onset RNDs. Methods: In this mixed‐methodology cross‐sectional study, 20 healthcare professionals (clinicians, genetic counsellors and scientists) and 20 carers completed qualitative semistructured interviews and custom‐designed surveys. Carers undertook validated psychosocial questionnaires. Thematic and quantitative data analysis followed. Results: Participants described high positive interest in advanced therapies, but low knowledge of, and access to, reliable information. The substantial 'therapeutic gap' and 'therapeutic odyssey' common to RNDs were recognised in five key themes: (i) unmet need and urgency for access; (ii) seeking information; (iii) access, equity and sustainability; (iv) a multidisciplinary and integrated approach to care and support and (v) difficult decision‐making. Participants were motivated to intensify RND clinical trial activity and access to advanced therapies; however, concerns around informed consent, first‐in‐human trials and clinical trial procedures were evident. There was high‐risk tolerance despite substantial uncertainties and knowledge gaps. RNDs with high mortality, increased functional burdens and no alternative therapies were consistently prioritised for the development of advanced therapies. However, little consensus existed on prioritisation to treatment access. Conclusions: This study highlights the need to increase clinician and health system readiness for the clinical translation of advanced therapeutics for RNDs. Co‐development and use of educational and psychosocial resources to support clinical decision‐making, set therapeutic expectations and promotion of equitable, effective and safe delivery of advanced therapies are essential. Patient or Public Contribution: Participant insights into the psychosocial burden and information need to enhance the delivery of care in this formative study are informing ongoing partnerships with families, including co‐production and dissemination of psychoeducational resources featuring their voices hosted on the Sydney Children's Hospitals Network website SCHN Brain-Aid Resources. [ABSTRACT FROM AUTHOR]

BackgroundSince 2014, the USA has documented three outbreaks of acute flaccid myelitis (AFM). Unique features and treatment responses of this myelitis variant have not been prospectively studied. This study prospectively measured outcomes in paediatric myelitis patients relative to treatments.MethodsThis was a prospective, multicentre, non-randomised, observational cohort study. The study duration was 5 years and the length of follow-up was 1 year. This study collected data from children and families in North America. Patients were enrolled at academic centres with expertise in myelitis or online via a web portal. Paediatric patients diagnosed with myelitis were eligible for enrolment in the study within 6 months of onset of symptoms. Patients were characterised as transverse myelitis (TM) or the AFM variant based on clinical and radiographic findings.ResultsThe cohort of 90 patients included patients with AFM and TM. Of the 51 patients with AFM there was evidence of two clinically relevant patterns. This included a grey matter restricted form of AFM and a cohort with concomitant white matter that could explain lower extremity motor deficits in patients with lesions restricted to the cervical spine. The improvement in deficits with the use of corticosteroids was similar to what was observed in the TM cohort (p=0.97).ConclusionsClinicians should consider on a case by case basis the approach to therapy for AFM patients. Prospective controlled studies of long-term outcomes would be useful in this growing patient population.

To compare the efficacy and safety of newer and/or second-line disease-modifying treatments (DMTs) with interferon beta-1a. This observational retrospective study included patients younger than 18 years old in the French KIDBIOSEP cohort who had a diagnosis of relapsing multiple sclerosis between 2008 and 2019 and received at least one DMT. Primary outcome was the annualized relapse rate (ARR). Secondary outcomes were the risk of new T2 or gadolinium-enhanced lesions on brain MRI. Among 78 patients enrolled, 50 were exposed to interferon and 76 to newer DMTs. Mean ARR went from 1.65 during pre-treatment period to 0.45 with interferon (p < 0.001). Newer DMTs reduced ARR compared to interferon: fingolimod 0.27 (p = 0.013), teriflunomide 0.25 (p = 0.225), dimethyl-fumarate 0.14 (p = 0.045), natalizumab 0.03 (p = 0.007). Risk of new lesions on MRI was reduced with interferon compared to pre-treatment period; it decreased even more with newer DMTs for T2 lesions. Regarding risk of new gadolinium-enhanced lesions, the added value of new treatments compared to interferon was less obvious, except for natalizumab (p = 0.031). In this real-world setting, newer DMTs showed better efficacy than interferon beta-1a on ARR and risk of new T2 lesions, with a good safety profile. Natalizumab tend to emerge as the most effective treatment. [ABSTRACT FROM AUTHOR]

Abstract Introduction Biomedical progress has facilitated breakthrough advanced neurotherapeutic interventions, whose potential to improve outcomes in rare neurological diseases has increased hope among people with lived experiences and their carers. Nevertheless, gene, somatic cell and other advanced neurotherapeutic interventions carry significant risks. Rare disease patient organizations (RDPOs) may enhance patient experiences, inform expectations and promote health literacy. However, their perspectives are understudied in paediatric neurology. If advanced neurotherapeutics is to optimize RDPO contributions, it demands further insights into their roles, interactions and support needs. Methods We used a mixed‐methodology approach, interviewing 20 RDPO leaders representing paediatric rare neurological diseases and following them up with two online surveys featuring closed and open‐ended questions on advanced neurotherapeutics (19/20) and negative mood states (17/20). Qualitative and quantitative data were analysed using thematic discourse analysis and basic descriptive statistics, respectively. Results Leaders perceived their roles to be targeted at educational provision (20/20), community preparation for advanced neurotherapeutic clinical trials (19/20), information simplification (19/20) and focused research pursuits (20/20). Although most leaders perceived the benefits of collaboration between stakeholders, some cited challenges around collaborative engagement under the following subthemes: conflicts of interest, competition and logistical difficulties. Regarding neurotherapeutics, RDPO leaders identified support needs centred on information provision, valuing access to clinician experts and highlighting a demand for co‐developed, centralized, high‐level and understandable, resources that may improve information exchange. Leaders perceived a need for psychosocial support within themselves and their communities, proposing that this would facilitate informed decision‐making, reduce associated psychological vulnerabilities and maintain hope throughout neurotherapeutic development. Conclusion This study provides insights into RDPO research activities, interactions and resource needs. It reveals a demand for collaboration guidelines, central information resources and psychosocial supports that may address unmet needs and assist RDPOs in their advocacy. Patient or Public Contribution In this study, RDPO leaders were interviewed and surveyed to examine their perspectives and roles in advanced neurotherapeutic development. Some participants sent researchers postinterview clarification emails regarding their responses to questions.

Background and Objectives: The clinical diagnosis of Huntington disease (HD) is typically made once motor symptoms and chorea are evident. Recent reports highlight the onset of cognitive and psychiatric symptoms before motor manifestations. These findings support further investigations of cognitive function across the lifespan of HD sufferers.Methods: To assess cognitive symptoms in the developing brain, we administered assessments from the National Institutes of Health Toolbox Cognitive Battery, an age-appropriate cognitive assessment with population norms, to a cohort of children, adolescents and young adults with (gene-expanded; GE) and without (gene-not-expanded; GNE) the trinucleotide cytosine, adenine, guanine (CAG) expansion in the Huntingtin gene. These five assessments that focus on executive function are well validated and form a composite score, with population norms. We modelled these scores across age, and CAP score to estimate the slope of progression, comparing these results to motor symptoms.Results: We find significant deficits in the composite measure of executive function in GE compared with GNE participants. GE participant performance on working memory was significantly lower compared with GNE participants. Modelling these results over age suggests that these deficits occur as early as 18 years of age, long before motor manifestations of HD.Conclusions: This work provides strong evidence that impairments in executive function occur as early as the second decade of life, well before anticipated motor onset. Future investigations should delineate whether these impairments in executive function are due to abnormalities in neurodevelopment or early sequelae of a neurodegenerative process. [ABSTRACT FROM AUTHOR]

Abstract Background The patient voice is becoming increasingly prominent across all stages of therapeutic innovation. It pervades research domains from funding and recruitment, to translation, care, and support. Advances in genomic technologies have facilitated novel breakthrough therapies, whose global developments, regulatory approvals, and confined governmental subsidisations have stimulated renewed hope amongst rare disease patient organisations (RDPOs). With intensifying optimism characterising the therapeutic landscape, researcher-advocate partnerships have reached an inflexion point, at which stakeholders may evaluate their achievements and formulate frameworks for future refinement. Main text Through this narrative review, we surveyed relevant literature around the roles of RDPOs catering to the rare paediatric neurological disease community. Via available literature, we considered RDPO interactions within seven domains of therapeutic development: research grant funding, industry sponsorship, study recruitment, clinical care and support, patient-reported outcome measures, and research prioritisation. In doing so, we explored practical and ethical challenges, gaps in understanding, and future directions of inquiry. Current literature highlights the increasing significance of ethical and financial challenges to patient advocacy. Biomedical venture philanthropy is gaining momentum amongst RDPOs, whose small grants can incrementally assist laboratories in research, training, and pursuits of more substantial grants. However, RDPO seed funding may encounter long-term sustainability issues and difficulties in selecting appropriate research investments. Further challenges include advocate-industry collaborations, commercial biases, and unresolved controversies regarding orphan drug subsidisation. Beyond their financial interactions, RDPOs serve instrumental roles in project promotion, participant recruitment, biobank creation, and patient registry establishment. They are communication conduits between carers, patients, and other stakeholders, but their contributions may be susceptible to bias and unrealistic expectations. Conclusion Further insights into how RDPOs navigate practical and ethical challenges in therapeutic development may enhance cooperative efforts. They may also inform resources, whose distribution among advocates, parents, and clinicians, may assist decision-making processes around rare disease clinical trials and treatments.

Introduction: Biomedical progress has facilitated breakthrough advanced neurotherapeutic interventions, whose potential to improve outcomes in rare neurological diseases has increased hope among people with lived experiences and their carers. Nevertheless, gene, somatic cell and other advanced neurotherapeutic interventions carry significant risks. Rare disease patient organizations (RDPOs) may enhance patient experiences, inform expectations and promote health literacy. However, their perspectives are understudied in paediatric neurology. If advanced neurotherapeutics is to optimize RDPO contributions, it demands further insights into their roles, interactions and support needs. Methods: We used a mixed‐methodology approach, interviewing 20 RDPO leaders representing paediatric rare neurological diseases and following them up with two online surveys featuring closed and open‐ended questions on advanced neurotherapeutics (19/20) and negative mood states (17/20). Qualitative and quantitative data were analysed using thematic discourse analysis and basic descriptive statistics, respectively. Results: Leaders perceived their roles to be targeted at educational provision (20/20), community preparation for advanced neurotherapeutic clinical trials (19/20), information simplification (19/20) and focused research pursuits (20/20). Although most leaders perceived the benefits of collaboration between stakeholders, some cited challenges around collaborative engagement under the following subthemes: conflicts of interest, competition and logistical difficulties. Regarding neurotherapeutics, RDPO leaders identified support needs centred on information provision, valuing access to clinician experts and highlighting a demand for co‐developed, centralized, high‐level and understandable, resources that may improve information exchange. Leaders perceived a need for psychosocial support within themselves and their communities, proposing that this would facilitate informed decision‐making, reduce associated psychological vulnerabilities and maintain hope throughout neurotherapeutic development. Conclusion: This study provides insights into RDPO research activities, interactions and resource needs. It reveals a demand for collaboration guidelines, central information resources and psychosocial supports that may address unmet needs and assist RDPOs in their advocacy. Patient or Public Contribution: In this study, RDPO leaders were interviewed and surveyed to examine their perspectives and roles in advanced neurotherapeutic development. Some participants sent researchers postinterview clarification emails regarding their responses to questions. [ABSTRACT FROM AUTHOR]

Background: High-level evidence for using steroids in epileptic encephalopathy (EE), other than West syndrome (WS), is lacking. This study investigated the efficacy and safety of pulse intravenous methylprednisolone (IVMP) in EE other than WS.Methods: This is an open-label evaluator-blinded randomised controlled study. Children aged 6 months or more with EE other than WS were included. Eighty children were randomised into intervention and non-intervention groups with 40 in each group. At the first visit (T1) seizure frequency, electroencephalographic (EEG) and Vineland Social Maturity Scale (VSMS) were obtained, and antiseizure medication (ASM) were optimised. After 1 month (T2), subjects were randomised to intervention (ASM+3 months IVMP pulse) or non-intervention group (only ASM) with 40 subjects in each group. They were followed up for 4 months (T3) and assessed.Results: After 4 months of follow-up, 75% of patients receiving IVMP had >50% seizure reduction versus 15.4% in control group (χ2=28.29, p<0.001) (RR 4.88, 95% CI 2.29 to 10.40), median percentage change in seizure frequency (91.41% vs 10%, p<0.001), improvement in EEG (45.5% vs 9.4%, χ2=10.866, p=0.001) and social age domain of VSMS scores (Z=-3.62, p<0.001) compared with baseline. None of the patients in the intervention group had any serious side-effects.Discussion: Three-month pulse IVMP therapy showed significant improvement in seizure frequency, EEG parameters and VSMS scores, with no steroid-related serious adverse effects. It can be considered as a safe and effective add on treatment in children with EE other than WS.Trial Registration Number: CTRI/2019/02/017807. [ABSTRACT FROM AUTHOR]

Background: The patient voice is becoming increasingly prominent across all stages of therapeutic innovation. It pervades research domains from funding and recruitment, to translation, care, and support. Advances in genomic technologies have facilitated novel breakthrough therapies, whose global developments, regulatory approvals, and confined governmental subsidisations have stimulated renewed hope amongst rare disease patient organisations (RDPOs). With intensifying optimism characterising the therapeutic landscape, researcher-advocate partnerships have reached an inflexion point, at which stakeholders may evaluate their achievements and formulate frameworks for future refinement. Main text: Through this narrative review, we surveyed relevant literature around the roles of RDPOs catering to the rare paediatric neurological disease community. Via available literature, we considered RDPO interactions within seven domains of therapeutic development: research grant funding, industry sponsorship, study recruitment, clinical care and support, patient-reported outcome measures, and research prioritisation. In doing so, we explored practical and ethical challenges, gaps in understanding, and future directions of inquiry. Current literature highlights the increasing significance of ethical and financial challenges to patient advocacy. Biomedical venture philanthropy is gaining momentum amongst RDPOs, whose small grants can incrementally assist laboratories in research, training, and pursuits of more substantial grants. However, RDPO seed funding may encounter long-term sustainability issues and difficulties in selecting appropriate research investments. Further challenges include advocate-industry collaborations, commercial biases, and unresolved controversies regarding orphan drug subsidisation. Beyond their financial interactions, RDPOs serve instrumental roles in project promotion, participant recruitment, biobank creation, and patient registry establishment. They are communication conduits between carers, patients, and other stakeholders, but their contributions may be susceptible to bias and unrealistic expectations. Conclusion: Further insights into how RDPOs navigate practical and ethical challenges in therapeutic development may enhance cooperative efforts. They may also inform resources, whose distribution among advocates, parents, and clinicians, may assist decision-making processes around rare disease clinical trials and treatments. [ABSTRACT FROM AUTHOR]

Introduction: Telemedicine is a real-time interactive communication method where patients are assessed and treated remotely. Epilepsy is one of the most frequent neurological disorders in childhood. However, specialists and subspecialists are scarce in rural settings. In neurology, telemedicine has been shown to be useful in the treatment of epilepsy and other neurodevelopmental disorders. Methods: We gathered data from patients diagnosed with epilepsy and managed through telemedicine consultations from January 2011 to February 2020. We collected data on the number of consultations, town/city of origin, treatment, aetiology, seizure type, treatment adherence, loss to follow up, discharges, and comorbidities. Results: We identified a total of 467 patients (180 girls and 287 boys). The largest age group was pre-school children, with 160 cases (34.2%). Seizures were focal in 253 cases (54.2%) and generalised in 214 (45.8%). Seizure aetiology was unknown in the majority of patients (69.3%). Ninety percent of patients presented good treatment adherence, and 76.8% were seizure-free. Regarding treatment, 351 patients (75%) were receiving monotherapy, and the most frequently prescribed drug was magnesium valproate, in 225 patients (64.2%). A total of 158 patients (33.8%) presented 1 comorbidity, and 19 (4%) presented 2 comorbidities. Conclusions: In our study, telemedicine proved to be effective in the treatment and follow-up of paediatric patients with epilepsy living in rural settings. Its usefulness in other neuropaediatric disorders should also be evaluated. Resumen: Introducción: La telemedicina es un método de comunicación interactiva en tiempo real donde los pacientes son valorados y tratados por el médico en diferentes ubicaciones. La epilepsia es de los padecimientos neurológicos más frecuentes en la infancia. Es conocida la dificultad de contar con especialistas y subespecialistas en áreas no urbanas. En neurología, la telemedicina ha demostrado el beneficio en el tratamiento de epilepsia y otros trastornos del neurodesarrollo. Método: Se revisó la base de datos de telemedicina de enero del 2011 a febrero 2020 con diagnóstico de epilepsia. Se obtuvo número de consultas recibidas, ciudad de origen, tratamiento, etiología, tipo de crisis, apego al tratamiento, pacientes desertados, altas y comorbilidades. Resultados: Se identificaron 467 pacientes, 180 femeninas y 287 masculinos. Por edad el grupo predominante fue el prescolar con 160 casos (34.2%). Respecto al tipo de crisis epiléptica 253 pacientes presentaron crisis focales (54.2%) y 214 crisis generalizadas (45.8%). La etiología más frecuente es la desconocida con 69.3% de casos. El 90% tienen buen apego al tratamiento y el 76.8% se encuentran sin crisis. 351 pacientes se encuentran con monoterapia (75%) y el fármaco más utilizado es el valproato de magnesio en 225 (64.2%). 158 pacientes presentan 1 comorbilidad (33.8%) y 19 con 2 comorbilidades (4%). Conclusiones: La telemedicina es una herramienta digital que en nuestro estudio demostró ser eficaz en el tratamiento y seguimiento de pacientes pediátricos epilépticos en comunidades rurales de nuestra entidad. Debe seguir valorándose su utilidad en otros trastornos neuropediátricos.

Background: Mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes (MELAS) syndrome is one of the most well‐known mitochondrial diseases, with most cases attributed to m.3243A>G. MELAS syndrome patients typically present in the first two decades of life with a broad, multi‐systemic phenotype that predominantly features neurological manifestations––stroke‐like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses. Methods: A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed. Results: Three children were included in this case series. All patients presented with seizures and had MRI changes not confined to a single vascular territory. Blood heteroplasmy varied considerably, and one patient required a muscle biopsy. Based on a literature review of 114 patients, the mean age of presentation is 8.1 years and seizures are the most prevalent manifestation of stroke‐like episodes. Heteroplasmy is higher in a tissue other than blood in most cases. Conclusion: The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A>G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered. [ABSTRACT FROM AUTHOR]

Background and Objectives: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy and often presents during childhood. Guidelines for the optimal management of common problems experienced by individuals with CMT do not exist, for either children or adults. We formed the Paediatric CMT Best Practice Guidelines Consortium to develop evidence and consensus-based recommendations for the clinical management of children and adolescents with CMT, with the primary objective of promoting optimal, standardised care globally.Methods: Development of this clinical practice guideline involved a series of systematic reviews covering 10 clinical questions, modified Delphi methodology involving an international panel of clinicians to generate consensus where evidence did not exist, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the body of literature and formulate recommendations.Results: The final guideline includes three evidence-based and 31 consensus-based recommendations. They encompass the management of muscle weakness, balance and mobility impairment, sensory symptoms, muscle cramps, impaired upper limb function, respiratory impairment, maintenance of joint range of motion and non-surgical management of joint deformity. Consensus was not achieved in some management areas, reflecting differences in practice between clinicians and healthcare settings, and highlighting the need for further research.Conclusions: This clinical practice guideline provides practical and implementable guidance on the management of common clinical problems experienced by children with CMT and advocates for improved access to multidisciplinary care. Successful dissemination and implementation of these recommendations will be critical in ensuring their application across multiple healthcare settings. [ABSTRACT FROM AUTHOR]

Objective: To describe onset clinical features predicting time to first relapse and time to long-term visual, motor and cognitive disabilities in paediatric-onset aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSDs).Methods: In this retrospective UK multicentre cohort study, we recorded clinical data of paediatric-onset AQP4-IgG NMOSD. Univariate and exploratory multivariable Cox proportional hazard models were used to identify long-term predictors of permanent visual disability, Expanded Disability Status Scale (EDSS) score of 4 and cognitive impairment.Results: We included 49 paediatric-onset AQP4-IgG patients (38.8% white, 34.7% black, 20.4% Asians and 6.1% mixed), mean onset age of 12±4.1 years, and 87.7% were female. Multifocal onset presentation occurred in 26.5% of patients, and optic nerve (47%), area postrema/brainstem (48.9%) and encephalon (28.6%) were the most involved areas. Overall, 52.3% of children had their first relapse within 1 year from disease onset. Children with onset age <12 years were more likely to have an earlier first relapse (p=0.030), despite showing no difference in time to immunosuppression compared with those aged 12-18 years at onset. At the cohort median disease duration of 79 months, 34.3% had developed permanent visual disability, 20.7% EDSS score 4 and 25.8% cognitive impairment. Visual disability was associated with white race (p=0.032) and optic neuritis presentations (p=0.002). Cognitive impairment was predicted by cerebral syndrome presentations (p=0.048), particularly if resistant to steroids (p=0.034).Conclusions: Age at onset, race, onset symptoms and resistance to acute therapy at onset attack predict first relapse and long-term disabilities. The recognition of these predictors may help to power future paediatric clinical trials and to direct early therapeutic decisions in AQP4-IgG NMOSD. [ABSTRACT FROM AUTHOR]

Objectives: To provide an overview of the outcome measures currently used after sports-related concussion (SRC) in adolescents, categorising by the constructs they assess, follow-up duration and their feasibility of use., Design: Scoping review., Data Sources: We searched three electronic databases (MEDLINE, EMBASE and CINAHL). We also undertook citation tracking of the included articles and searched for ongoing or unpublished trials using ClinicalTrials.gov and Theses Global., Eligibility Criteria: Studies tracking concussion recovery in adolescent athletes., Results: 15 782 records were identified. After initial title and abstract screening, we retrieved 87 studies for full-text screening, with 75 studies fulfilling the eligibility criteria and included in the review, comprising 13 107 participants (9480 male, 3615 female and 12 unreported), ranging in age from 5 to 19 years. 46 different outcome measures were used, with Post-Concussion Symptom Scale (n=42) and Immediate Post-Concussion Assessment and Cognitive Testing (n=21) the most common. Most outcome measures quantified aspects of sensorimotor function including balance, oculomotor function and cognition. Follow-up duration ranged from 7 days to 1 year. 60% of studies ceased follow-up assessments within 6 weeks post-SRC., Conclusions: Adolescent SRC literature uses a wide range of outcome measures. Most research quantifies cognitive/fatigue domains in the acute/subacute stages post-SRC, using male participants. Other key domains such as anxiety/mood, migraine and key modifiers (cervical and sleep disturbance) are less well represented in the literature. Many of the outcome measures used in current research are associated with high cost and require highly qualified examiners, creating barriers to their implementation in some adolescent sporting environments., Study Registration: https://doi.org/10.17605/OSF.IO/N937E., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This investigation evaluates the effectiveness and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) as a treatment modality for drug-resistant epilepsy., Material and Methods: A retrospective review of clinical data from 40 paediatric patients with drug-resistant epilepsy, who underwent SEEG-guided RF-TC at our Epilepsy Center between 2020 and 2022, was conducted. This review included the patients' medical history, imaging and electroencephalography results, surgical procedures, and follow-up outcomes., Results: The duration of SEEG monitoring, accompanied by concurrent electrical stimulation tests, varied from 3 days to 4 weeks. Following RF-TC surgery, 4 patients demonstrated temporary neurological impairments, including central facial and tongue weakness, reduced limb strength, and challenges in fine motor hand movements. All these symptoms were related to lesions in the central region, but showed improvement within 2 weeks to 3 months post-surgery. There were no reported instances of status epilepticus, intracranial haemorrhage, or infections. During a follow-up period of 6 months to 2.5 years, seizure control was achieved in 25 patients (62.5%) at 6 months post-surgery, and a > 50% decrease in seizure frequency was observed in 10 patients. In 5 patients where seizure control was not achieved, the management of epilepsy seemed to be independent of factors such as age at surgery, duration of preoperative disease, seizure type, or negative MRI findings ( p > 0.05). Patients with controlled epilepsy exhibited cognitive improvement, with some demonstrating no EEG abnormalities upon follow-up and a decrease in antiepileptic medication., Conclusions: SEEG-guided RF-TC appears to be a potentially effective and safe therapeutic approach for paediatric patients with drug-resistant epilepsy.

Objectives: To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study., Design: This study was a prospective birth cohort study., Setting: This study population included 104 059 fetal records who participated in The Japan Environment and Children's Study from 2011 to 2014., Participants: Pregnant women whose children had undergone developmental testing were included in this analysis., Primary and Secondary Outcome Measures: Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development., Results: Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers., Conclusion: An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Children with CHD are at heightened risk of neurodevelopmental problems; however, the contribution of acute neurological events specifically linked to the perioperative period is unclear., Aims: This secondary analysis aimed to quantify the incidence of acute neurological events in a UK paediatric cardiac surgery population, identify risk factors, and assess how acute neurological events impacted the early post-operative pathway., Methods: Post-operative data were collected prospectively on 3090 consecutive cardiac surgeries between October 2015 and June 2017 in 5 centres. The primary outcome of analysis was acute neurological event, with secondary outcomes of 6-month survival and post-operative length of stay. Patient and procedure-related variables were described, and risk factors were statistically explored with logistic regression., Results: Incidence of acute neurological events after paediatric cardiac surgery in our population occurred in 66 of 3090 (2.1%) consecutive cardiac operations. 52 events occurred with other morbidities including renal failure (21), re-operation (20), cardiac arrest (20), and extracorporeal life support (18). Independent risk factors for occurrence of acute neurological events were CHD complexity 1.9 (1.1-3.2), p = 0.025, longer operation times 2.7 (1.6-4.8), p < 0.0001, and urgent surgery 3.4 (1.8-6.3), p < 0.0001. Unadjusted comparison found that acute neurological event was linked to prolonged post-operative hospital stay (median 35 versus 9 days) and poorer 6-month survival (OR 13.0, 95% CI 7.2-23.8)., Conclusion: Ascertainment of acute neurological events relates to local measurement policies and was rare in our population. The occurrence of acute neurological events remains a suitable post-operative metric to follow for quality assurance purposes.

Background: Recent years have seen considerable changes in the prevention and treatment of acute ischaemic stroke in adult patients. However, the low incidence of paediatric stroke makes the development of specific guidelines more challenging. This study aims to clarify the situation of these children in our region in order to establish a regional protocol to improve the care provided to these patients., Methods: We performed a regional incidence study of pediatric stroke (≤ 15 years of age) in Aragon, Spain (1308728 population, 15% aged ≤ 15 years) between 2008 and 2019. Data were obtained from hospital discharge records, including deaths, from the regional health service of Aragón, according to ICD codes for cerebrovascular disease. We analysed demographic, clinical, diagnostic/therapeutic, and prognostic variables., Results: A total of 21 events were recorded: 8 ischaemic (38.1%) and 13 haemorrhagic strokes (61.9%). The mean age (SD) was 9.3 years (1.0). The sample included 12 boys and nine girls. No statistically significant differences were found between ischaemic and haemorrhagic strokes, except in the chief complaint (language and motor impairment in ischaemic stroke and headache in haemorrhagic stroke). None of the patients with ischaemic stroke received reperfusion therapies. Including the 3 patients who died during hospitalisation, eight patients (42.1%) had modified Rankin Scale scores > 2 at 12 months. Motor deficits were the most common sequela (n=9)., Conclusion: Though infrequent, paediatric stroke has an important functional impact. In Spain, Madrid was the first region to adapt the existing code stroke care networks for adult patients. In Aragon, this review has enabled us to work closely with the different stakeholders to offer a care plan for acute paediatric ischaemic stroke. Nevertheless, prospective national registries would be valuable to continue improving the care provided to these patients., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

The abundant evidence linking epilepsy with hydroelectrolytical changes in epilepsy reported in the medical literature for over 9 decades is reviewed. Our work on this topic is presented, including the detection by NMR of a decreased water permeability of the red blood cells (RBCs) from children with epilepsy compared with control children. This was interpreted as a generalized membrane defect in epilepsy. The subsequent program of research performed by Gh. Benga's group in Cluj-Napoca led to the discovery of the first water channel protein (WCP) in the RBC membrane, protein later called aquaporin1 (AQP1). A lot of WCPs (AQPs and relatives) have been identified later by various authors, in the body of humans and many other species. The physiological roles of WCPs from the central nervous system (CNS) and their implications in epilepsy and other neurological diseases are reviewed, including the information published in the last months. [ABSTRACT FROM AUTHOR]

Genetic tests are an efficient and effective diagnostic tool in paediatric neurology, and are increasingly incorporated into the diagnostic work-up of our patients. Significant advances in genetic technologies in recent years has expanded both the scale at which genetic testing can be done, and the speed with which results can be returned. However, there is no "perfect" genetic test which will identify all clinically relevant genetic variants. Understanding the appropriate application of each test type is therefore key to securing a diagnosis. It is vital that consent to genetic testing is freely given and adequately informed. In this article, using clinical vignettes, we will discuss the strengths and limitations of each genetic test, and give an overview of how to take informed consent. Our ability to identify variants has outstripped our ability to interpret them reliably so caution should be exercised. We describe the challenges of variant interpretation, and the importance of Clinical Genetics expertise in this process. [ABSTRACT FROM AUTHOR]

Introduction: Around 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality. Often little is known about expected growth and phenotypes in these children. Parents have responded by setting up social media groups to generate data themselves. Given the significant clinical evidence gaps, this research will attempt to identify growth patterns, developmental profiles and phenotypes, providing data on long-term medical and educational outcomes. This will guide clinicians when to investigate, monitor or treat symptoms and when to search for additional or alternative diagnoses., Methods and Analysis: This is an observational, multicentre cohort study recruiting between March 2023 and February 2026. Children aged 6 months up to 16 years with a pathogenic or likely pathogenic variant in a specified gene will be eligible. Children will be identified through the National Health Service and via self-recruitment. Parents or carers will complete a questionnaire at baseline and again 1 year after recruitment. The named clinician (in most cases a clinical geneticist) will complete a clinical proforma which will provide data from their most recent clinical assessment. Qualitative interviews will be undertaken with a subset of parents partway through the study. Growth and developmental milestone curves will be generated through the DECIPHER website (https://deciphergenomics.org) where 5 or more children have the same genetic syndrome (at least 10 groups expected)., Ethics and Dissemination: The results will be presented at national and international conferences concerning the care of children with genetic syndromes. Results will also be submitted for peer review and publication., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Lesion resolution is often observed in children with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and asymptomatic lesions are less commonly reported in MOGAD than in multiple sclerosis (MS)., Objective: We aimed to evaluate brain MRI changes over time in paediatric MOGAD., Methods: Retrospective study in eight UK paediatric neuroscience centres. Acute brain MRI and available follow-up MRIs were reviewed. Predictors for lesion dynamic were evaluated using multivariable regression and Kaplan-Meier survival analyses were used to predict risk of relapse, disability and MOG-Ab status., Results: 200 children were included (MOGAD 97; MS 103). At first MRI post attack, new symptomatic and asymptomatic lesions were seen more often in MS versus MOGAD (52/103 vs 28/97; p=0.002 and 37/103 vs 11/97; p<0.001); 83% of patients with MOGAD showed at least one lesion's resolution at first follow-up scan, and 23% had normal MRI. Only 1 patient with MS had single lesion resolution; none had normal MRI. Disappearing lesions in MOGAD were seen in 40% after the second attack, 21% after third attack and none after the fourth attack.New lesions at first follow-up scan were associated with increased likelihood of relapse (p=0.02) and persistent MOG-Ab serostatus (p=0.0016) compared with those with no new lesions. Plasma exchange was associated with increased likelihood of lesion resolution (p=0.01). Longer time from symptom onset to steroids was associated with increased likelihood of new lesions; 50% increase at 20 days (p=0.01)., Conclusions: These striking differences in lesion dynamics between MOGAD and MS suggest greater potential to repair. Early treatment with steroids and plasma exchange is associated with reduced likelihood of new lesions., Competing Interests: Competing interests: OA-m receives funding from the Association British Neurologists, MS Society and the Berkeley Foundation’s AW Pidgley Memorial Trust. RF has received grant funding from the NIHR Efficacy and Mechanism Evaluation Programme. CH has received educational and travel grants from Merck Serono and Bayer and Biogen. ML receives research grants from Action Medical Research, the DES society, GOSH charity, National Institute for Health Research, MS Society, and SPARKS charity; receives research support grants from the London Clinical Research Network and Evelina Appeal; has received consultation fees from CSL Behring, Novartis and Octapharma; received travel grants from Merck Serono. OC is a member of independent DSMB for Novartis, gave a teaching talk on McDonald criteria in a Merck local symposium, and contributed to an Advisory Board for Biogen; she is Deputy Editor of Neurology, for which she receives an honorarium., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Psychomotor retardation refers to a situation when a child does not attain developmental milestones in the right time, i.e. he or she is unable to master skills that should develop at a given stage of life. Child development proceeds in strictly correlated phases. To attain a higher developmental level, one must first acquire and consolidate the lower level. The maturation of the central nervous system is quite intensive, even prenatally. Its individual structures develop in a specified order, depending on the week of gestation. Brain immaturity is a frequent cause of psychomotor retardation in children. The nervous tissue is composed of neurones (their cell membranes consist of a double lipid layer) and glial cells. Neurones form up to the 20th week of gestation, while glial cell formation starts after birth. This intensive development of the central nervous system may be accompanied by certain defects that will result in psychomotor retardation, which is also influenced by various physiological processes occurring in the child’s life. The type of damage and the grade of its severity depend on its location, area of pathological brain tissue and age at which the defect occurred. Injuries that cause psychomotor retardation in children may be divided into microinjuries, macroinjuries as well as endo- and exogenous causes. Psychomotor retardation is assessed on the Brunet–Lézine scale. It contains tasks that a child should be able to perform at a given stage of his or her development. The result is a psychomotor development quotient. Retardation may present as a complete deficit of given skills and their absence in the later stages of development. Psychomotor retardation may reveal itself at the beginning of the child’s life or in the later period. This depends on the causes of these limitations. The diagnosis of psychomotor retardation requires cooperation of various specialists.

Paediatric Neurology (PN) is a discipline focused on diagnosis, comprehensive management and research into diseases of the central and peripheral nervous system from fetal life to transition into adulthood. The European Paediatric Neurology Society first designed and published the European PN training programme in the European Paediatric Neurology Syllabus in 2002. This was important in gaining recognition for the sub-specialty from the European Academy of Paediatrics and the European Academy of Neurology and in 2003 PN was recognized as a sub-specialty of paediatrics and neurology by the Board of the European Union of Medical Specialties. In 2004, the EPNS founded the Committee of National Advisors (CNA) that comprised representatives from national Paediatric Neurology societies, in order to further enhance Europe wide standards in training and practice., The EPNS Training Advisory Board (TAB) offers nation specific advice/support to PN societies on developing training and care systems. In 2019, the 2nd revision of the Paediatric Neurology Syllabus was approved by the EPNS Board and CNA. We aim to give an overview of the training of Paediatric Neurology (PN) specialists (i.e. Paediatric Neurologists), the relevant professional bodies and the current practice of Paediatric Neurology in Europe, as defined geographically by the World Health Organization. A structured online data collection form was completed by CNA representatives from European countries. The data included training routes and structure of training, epidemiological data, nature of professional societies, organization of Paediatric Neurology care, research, academic life and recognition of the specialty. Data was collected from 43 European countries of which 38 have a national PN Society. In 10 (6 European Union (EU) and 4 non-EU countries) PN is recognized as a core specialty. In 26 countries PN is recognized as a sub-specialty of Paediatrics, Neurology or both (15 EU-11 non-EU). PN is not recognized as a core or sub-specialty in 7 countries (4 EU and 3 non-EU). In 35 countries paediatric neurologists begin their training from Paediatrics, but in 19 countries PN training from Neurology is also possible or the preferred route. Training in PN differs, but in over 50% of countries the three main training modules named in the 2019 2nd revision of the European PN Syllabus (PN, Paediatrics and adult Neurology) are included. Many countries have already adapted their curriculum to the suggestions in the European PN syllabus. There is diversity among European countries in terms of professional organization and PN training. The European PN syllabus has had impact on the development of PN training throughout Europe, independent of duration of training or route from paediatrics or neurology. The syllabus provides a basis for the future development of PN training, the recognition of PN as a (sub) specialty in individual countries and for improving the care of children with neurological disorders in Europe. • A training programme, the European Paediatric Neurology Syllabus has been approved. • Paediatric Neurology is recognized as core or as sub-specialty of Paediatrics or Neurology, in 36/43 European countries. • Training and the practice of paediatric neurology differs greatly among European countries. • Many countries have developed their national curriculum in line with the European Paediatric Neurology Syllabus. • The European Paediatric Neurology Syllabus should act as the basis for further development of PN training in Europe • The European Paediatric Neurology Syllabus recommends a minimum of 5, but ideally 6 years training in paediatric neurology. [ABSTRACT FROM AUTHOR]

Children and young people (CYP) with neurodevelopmental disorders (NDDs) may be particularly vulnerable to adverse mental health effects due to the COVID-19 pandemic. We conducted a cross-sectional U.K. parent-reported study from 2nd April-2nd June 2020, using the Strengths and Difficulties Questionnaire. CYP with NDDs (n = 371), compared to neurotypical controls, had a higher prevalence of emotional symptoms (42% vs. 15%) and conduct problems (28% vs. 9%), and fewer prosocial behaviours (54% vs. 22%). All groups had worse emotional symptoms than pre-COVID groups, and those with attention-deficit/hyperactivity disorder showed inflated conduct problems, while those with autism spectrum disorder exhibited decreased prosocial behaviours. Females with ASDhad higher emotional symptoms compared to males. CYP with NDDs, and those without, showed higher levels of parent-reported mental health problems than comparable cohorts pre-COVID-19. [ABSTRACT FROM AUTHOR]

Dr Rajvinder Karda is a lecturer In gene therapy at the Institute for Women’s Health, University College London. She completed her PhD in gene transfer and neuroscience at Imperial College London in 2016. Her research team mainly focuses on developing preclinical gene therapy and RNA editing treatments for childhood epilepsy. She also collaborates on preclinical gene therapy projects for rare childhood metabolic disorders. She is currently a board member of the British Gene and Cell Therapy Society and chairs the Public and Patient Engagement series. She is also a member of the Scientific Advisory Committee for the Dravet Syndrome Foundation Charity in Spain. [ABSTRACT FROM AUTHOR]

Ehlers-Danlos syndromes (EDS) is an umbrella term describing 14 types, of which 13 are rare and monogenic, with overlapping features of joint hypermobility, skin, and vascular fragility, and generalised connective tissue friability. Hypermobile EDS currently has no identified genetic cause. Most of the rare monogenic EDS types can have neurological features, which are often part of major or minor diagnostic criteria for each type. This review aims to highlight the neurological features and other key characteristics of these EDS types. This should improve recognition of these features, enabling more timely consideration and confirmation or exclusion through genetic testing. In practice, many healthcare professionals still refer to patients as having 'EDS'. However, the different EDS types have distinct clinical features as well as different underlying genetic causes and pathogenic mechanisms, and each requires bespoke management and surveillance. Defining the EDS type is therefore crucial, as EDS is not in itself a diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Research using animal models suggests that intensive motor skill training in infants under 2 years old with cerebral palsy (CP) may significantly reduce, or even prevent, maladaptive neuroplastic changes following brain injury. However, the effects of such interventions to tentatively prevent secondary neurological damages have never been assessed in infants with CP. This study aims to determine the effect of the baby Hand and Arm Bimanual Intensive Therapy Including Lower Extremities (baby HABIT-ILE) in infants with unilateral CP, compared with a control intervention., Methods and Analysis: This randomised controlled trial will include 48 infants with unilateral CP aged (corrected if preterm) 6-18 months at the first assessment. They will be paired by age and by aetiology of the CP, and randomised into two groups (immediate and delayed). Assessments will be performed at baseline and at 1 month, 3 months and 6 months after baseline. The immediate group will receive 50 hours of baby HABIT-ILE intervention over 2 weeks, between first and second assessment, while the delayed group will continue their usual activities. This last group will receive baby HABIT-ILE intervention after the 3-month assessment. Primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes will include behavioural assessments for gross and fine motricity, visual-cognitive-language abilities as well as MRI and kinematics measures. Moreover, parents will determine and score child-relevant goals and fill out questionnaires of participation, daily activities and mobility., Ethics and Dissemination: Full ethical approval has been obtained by the Comité d'éthique Hospitalo-Facultaire/Université catholique de Louvain , Brussels (2013/01MAR/069 B403201316810g). The recommendations of the ethical board and the Belgian law of 7 May 2004 concerning human experiments will be followed. Parents will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations., Trial Registration Number: NCT04698395. Registered on the International Clinical Trials Registry Platform (ICTRP) on 2 December 2020 and NIH Clinical Trials Registry on 6 January 2021. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT04698395?term=bleyenheuft&draw=1&rank=7., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Type II spinal muscular atrophy (SMA) often leads to scoliosis in up to 90% of cases. While pharmacological treatments have shown improvements in motor function, their impact on scoliosis progression remains unclear. This study aims to evaluate potential differences in scoliosis progression between treated and untreated SMA II patients., Methods: Treatment effect on Cobb's angle annual changes and on reaching a 50° Cobb angle was analysed in treated and untreated type II SMA patients with a minimum 1.5-year follow-up. A sliding cut-off approach identified the optimal treatment subpopulation based on age, Cobb angle and Hammersmith Functional Motor Scale Expanded at the initial visit. Mann-Whitney U-test assessed statistical significance., Results: There were no significant differences in baseline characteristics between the untreated (n=46) and treated (n=39) populations. The mean Cobb angle variation did not significantly differ between the two groups (p=0.4). Optimal cut-off values for a better outcome were found to be having a Cobb angle <26° or an age <4.5 years. When using optimal cut-off, the treated group showed a lower mean Cobb variation compared with the untreated group (5.61 (SD 4.72) degrees/year vs 10.05 (SD 6.38) degrees/year; p=0.01). Cox-regression analysis indicated a protective treatment effect in reaching a 50° Cobb angle, significant in patients <4.5 years old (p=0.016)., Conclusion: This study highlights that pharmacological treatment, if initiated early, may slow down the progression of scoliosis in type II SMA patients. Larger studies are warranted to further investigate the effectiveness of individual pharmacological treatment on scoliosis progression in this patient population., Competing Interests: Competing interests: GC, MCP, AD'A, MP, RdS, MC, EB, MP and EM have been a consultant for BIOGEN S.R.L. which owns patent rights to nusinersen of which data from patients in treatment were used in this study. GC, MCP, AD'A, MP, RdS, MC, EB, MP and EM have been a consultant for ROCHE which owns patent rights to risdiplam of which data from patients in treatment were used in this study., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The International PANS Registry (IPR) Epidemiology Study is a registry-based, longitudinal study. We designed this study to improve phenotyping and characterisation of children with paediatric acute-onset neuropsychiatric syndrome (PANS) and PANS-like features and facilitate multidisciplinary and translational health research. This cohort provides new opportunities to address unresolved research questions related to the broad spectrum of heterogenous PANS-like conditions., Participants: Inclusion in the IPR Epidemiology Study remains open indefinitely via IPR enrolment online. Participants include children with PANS or who have PANS-like features and their healthy siblings. We collected cross-sectional survey data based on parent report, including details on phenotypic traits and characteristics that, to our knowledge, have not been previously collected for this patient population. We describe the baseline characteristics of cases and their healthy siblings here., Findings to Date: The IPR Epidemiology Study currently includes 1781 individuals (1179 cases, 602 siblings; from 1010 households). Many households include a sibling (n=390, 39%) and some include multiple cases (n=205, 20%). Mean enrolment age was 11.3±4.3 years for cases and 10.1±5.3 for siblings. Leading PANS-like features include anxiety (94%), emotional lability (92%) and obsessions (90%). Onsets were sudden and dramatic (27%), gradual with a subsequent sudden and dramatic episode (68%) or a gradual progression (5%). The mean age at early signs/symptom onset was 4 years and 7 years at sudden and dramatic increases, respectively. Infection/illness was the most common suspected symptom trigger (84%). Nearly all cases had been treated with antibiotics (88%) and/or non-steroidal anti-inflammatory drugs (79%). Parents reported immune-related conditions in cases (18%) and their nuclear, biological family (48%; 39% in biological mothers)., Future Plans: Future plans include increasing sample size, collecting longitudinal survey data, recruiting appropriate study controls and expanding the scope of the database, prioritising medical record data integration and creating a linked biorepository. Secondary data analyses will prioritise identifying subgroups by phenotypic traits, maternal health and disease characteristics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Children with seizures require immediate and appropriate intervention in the emergency department (ED). This study describes the clinical profile and outcome of paediatric patients with seizures at the ED in a country with limited resources., Design: A prospective, observational cohort study of paediatric patients with seizure presenting to an ED conducted over a six-month period from 1 August 2019 to 31 January2020., Setting: The study was conducted at the ED of Muhimbili National Hospital, a level 1 trauma centre located in Dar es Salaam, Tanzania., Participants: Paediatric patients aged 1 month to 14 years presenting at the ED with acute seizure, defined as any seizure occurring from 24 hours to 7 days prior to the visit, were included in this study. Patients were consecutively enrolled during times a research assistant was present in the department. Newborns, children with repeat visits or no signs of life on arrival were excluded., Outcome: The primary outcome was the proportion of paediatric patients presenting with seizures and their mortality rate; secondary outcome was risk factors for mortality., Result: During the study period, 1011 children were seen in the department, of whom 114 (11.3%) (95% CI 9.3% to 13.3%) presented with seizures. Median age was 24 months (IQR 9-60), 78.1% were under 5 years and 55.3% were males. The majority 76 (66.7%) of the patients presented with generalised seizures. Half 58 (50.9%) of patients presented with fever. Meningitis was the most common aetiology, diagnosed in 30 (26.3%). Overall mortality was 16.7% (95% CI 10.3% to 24.8%). Using negative log binominal analysis, fever (relative risk, RR 2.7), altered mental status (RR 21.1), hypoxia (RR 3.3), abnormal potassium (RR 2.4) and clinical diagnosis of meningitis (RR 3.4) were statistically significantly associated with mortality., Conclusions: Findings from this study revealed higher incidence of paediatric patients with seizures than that reported in high-income countries and other low-income and middle-income countries. The acuity of illness was high, with 16.7% mortality rate. The presence of fever, altered mental status, hypoxia, abnormal potassium levels and meningitis diagnosis were associated with higher risk of mortality. Further research is needed to develop interventions to improve outcomes in paediatric patients with seizures in our setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Delayed sleep phase disorder (DSPD) is a sleep disorder commonly affecting children, particularly those with neurological problems, such as autism and attention deficit hyperactivity disorder (ADHD). DSPD is characterised by difficulty in falling asleep, and it results from misalignment of the internal circadian clock with desired sleep time. For those children for whom good sleep hygiene practice is unsuccessful, supplementation with melatonin is standard practice. Randomised controlled studies have shown that strategically timed administration of melatonin, typically in the dose range 3–6 mg, is effective in advancing circadian rhythm and sleep onset in a clinically significant manner. Supplemental melatonin is available in two formulations, immediate-release and controlled-release; for sleep induction as required in DSPD, immediate-release melatonin is considered to be the more effective formulation, as supported by 19 randomised controlled clinical studies (comprising more than 800 individuals), together with a meta-analysis. The safety of supplemental melatonin administration in children, particularly in the short term, has been well documented. Melatonin supplementation is relevant to a number of aspects of neuroscience nursing; in addition to improving sleep onset in children with neurological disorders, melatonin supplementation may be of benefit in intensive care patients following brain injury, in patients with neurodegenerative disorders, and in nurses themselves to counter the detrimental effects of night-shift working. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to estimate the recurrence rate of culture-positive bacterial meningitis in children in the Netherlands., Design: Nationwide surveillance study, using the database of the Netherlands Reference Laboratory for Bacterial Meningitis to identify patients with culture-positive bacterial meningitis during childhood., Setting: The study was based in the Netherlands., Participants: A total of 9731 children with a first bacterial meningitis episode between 1 July 1987 and 30 June 2019 were identified., Primary and Secondary Outcome Measures: Recurrence was defined as a subsequent episode >28 days, or caused by a different pathogen. Annual incidence and incidence rate ratios (IRRs) comparing the periods 1988-2003 and 2004-2019 were calculated. Predictors of recurrent meningitis were assessed using Cox proportional hazards regression., Results: Sixty-three (0.6%) of the 9731 children with a first bacterial meningitis episode contracted recurrent meningitis. Neisseria meningitidis was the leading pathogen for first meningitis episodes (52%) and Streptococcus pneumoniae for recurrent episodes (52%). The median annual incidence of first episodes per 100 000 children decreased from 11.81 (IQR 11.26-17.60) in 1988-2003 to 2.60 (IQR 2.37-4.07) in 2004-2019 (IRR 0.25, 95% CI 0.23 to 0.26). The incidence of recurrences did not change: 0.06 (IQR 0.02-0.11) in 1988-2003 to 0.03 (IQR 0.00-0.06) in 2004-2019 (IRR 0.65, 95% CI 0.39 to 1.1). Age above 5 years (OR 3.6 (95% CI 1.5 to 8.3)) and a first episode due to Escherichia coli (OR 25.7 (95% CI 7.2 to 92.0)) were associated with higher risks of recurrence., Conclusion: The recurrence rate of childhood bacterial meningitis in the Netherlands was 0.6%. While the incidence rate of first episodes decreased substantially, this was not the case for recurrent episodes. Older age and a first episode due to E. coli were associated with higher recurrence risks., Competing Interests: Competing interests: NMvS receives consultancy fees from MSD and GSK (fees paid to Amsterdam UMC). In addition, NMvS has a patent WO 2013/020090 A3 (inventors: NMvS/V. Nizet) outside the submitted work with royalties paid to University of California San Diego. All sponsors had no role in study design, data collection and analysis, interpretation of the data, writing of the manuscript or decision to submit for publication. Other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness., Design: Phase 3b multicentre, double-blind, randomised placebo-controlled trial., Setting: Twenty-one hospitals in the UK., Participants: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308., Intervention: Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24-36 hours apart, in addition to standard treatment., Main Outcome Measure: The primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended., Secondary Outcome Measures: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data., Results: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG., Conclusions: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis., Trial Registration Number: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925., Competing Interests: Competing interests: MI was a trainee member on the NIHR Efficacy and Mechanism Evaluation Programme Funding Committee from October 2020 to October 2021. MA has received a grant from the NIHR in the last 36 months, for research unrelated to the submitted work. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines; all funds have been paid to his institute. Ava Easton is Chief Executive of the Encephalitis Society, which has previously received grants from CSL Behring (UK). Ming Lim has received grants from the GOSH charity, Boston Children’s Hospital Research Fund and Action Medical Research in the last 36 months, all for research unrelated to the submitted work. Ming Lim is co-chair of the European Paediatric Neurology Education and Training Board and works for an institution which holds research accounts with Roche (Switzerland), Octapharma (Switzerland) and Novartis (Switzerland). Tom Solomon is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, NIHR Programme Grant for Applied Research, NIHR Global Health Research on Brain Infections and the European Union’s Horizon 2020 research and innovation program ZikaPLAN. Tom Solomon is a consultant for the MHRA Vaccine Benefit Risk Expert Working Group. Angela Vincent is a consultant for Aspen NewCo Inc and has received honoraria from UCB and Alexion. L-MY was a member of the NIHR Health Technology Assessment Efficient Study Designs from November 2015 to July 2016. Andrew J Pollard is chair of the Department of Health and Social Care’s Joint committee on Vaccines and Immunisation (JCVI) and was a member of WHO’s SAGE until 1 January 2022. Oxford University has entered a partnership with AstraZenenca on COVID-19 vaccines, but Andrew Pollard does not participate in the JCVI COVID-19 committee., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Children with cerebral palsy (CP) participate less in physical activities and have increased sedentary behaviour compared with typically developing peers. Participate CP is a participation-focused therapy intervention for children with CP with demonstrated efficacy in a phase II randomised controlled trial (RCT) to increase perceived performance of physical activity participation goals. This study will test the effectiveness of Participate CP in a multisite phase III RCT., Methods and Analysis: One hundred children with CP, aged 8-14 years, classified Gross Motor Function Classification System levels I-IV will be randomised to either (1) receive Participate CP once/week for 1 hour for 12 weeks, or (2) waitlist control, usual care group. The waitlist group will then receive Participate CP following the 26-week retention time point. Outcomes will be assessed at baseline, 12 weeks and then 26 weeks post baseline. The primary outcomes are (1) self-reported participation goal performance on the Canadian Occupational Performance Measure at 12 weeks and (2) daily time in moderate-to-vigorous physical activity. Secondary outcomes include home and community participation frequency, involvement and environmental supportiveness, contextual barriers to participation, quality of life, intrinsic motivation for physical activities, child perception of an autonomy-supportive climate for physical activities and physical literacy at 12 and 26 weeks post study entry., Ethics and Dissemination: The Children's Health Queensland Hospital and Health Service, The University of Queensland and the New Zealand Health and Disability Ethics Committees have approved this study. Findings will be disseminated in peer-reviewed journals and conference presentations., Trial Registration Number: ACTRN12618000206224., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: Patients carrying pathogenic variants in GNAO1 often present with early-onset central hypotonia and global developmental delay, with or without epilepsy. As the disorder progresses, a complex hypertonic and hyperkinetic movement disorder is a common phenotype. A genotype-phenotype correlation has not yet been described and there are no evidence-based therapeutic recommendations., Methods: To improve understanding of the clinical course and pathophysiology of this ultra-rare disorder, we built up a registry for GNAO1 patients in Germany. In this retrospective, multicentre cohort study, we collected detailed clinical data, treatment effects and genetic data for 25 affected patients., Results: The main clinical features were symptom onset within the first months of life, with central hypotonia or seizures. Within the first year of life, nearly all patients developed a movement disorder comprising dystonia (84%) and choreoathetosis (52%). Twelve (48%) patients suffered life-threatening hyperkinetic crises. Fifteen (60%) patients had epilepsy with poor treatment response. Two patients showed an atypical phenotype and seven novel pathogenic variants in GNAO1 were identified. Nine (38%) patients were treated with bilateral deep brain stimulation of the globus pallidus internus. Deep brain stimulation reduced hyperkinetic symptoms and prevented further hyperkinetic crises. The in silico prediction programmes did not predict the phenotype by the genotype., Conclusion: The broad clinical spectrum and genetic findings expand the phenotypical spectrum of GNAO1 -associated disorder and therefore disprove the assumption that there are only two main phenotypes. No specific overall genotype-phenotype correlation was identified. We highlight deep brain stimulation as a useful treatment option in this disorder., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Autoimmune-mediated processes are the driving force behind many neurological diseases. Autoimmune encephalitis, a group of syndromes, mediated by or at least associated with autoantibodies against neuronal tissue, have gained increasing importance especially in paediatric neurology. Since the first NMDAR encephalitis was described a growing number of patients with encephalopathy, seizures and psychiatric symptoms were found to suffer from treatable autoimmune disorders. Recently a severe form of encephalitis associated with GABA A R antibodies was described showing extensive MRI abnormalities and refractory seizures. Case We now describe a child with catatonia and encephalopathy due to antibodies against the GABA A receptor. It is a rare paediatric case without the development of seizures despite severe encephalopathy. Relevance The report extends the phenotype of this rare disease. It demonstrates a favourable outcome after introduction of an early and aggressive immunomodulatory therapy. Due to the child's history of previous viral meningitis, the case raises questions about the unrevealed mechanisms leading to autoimmune encephalitis, including the model of a viral trigger as discussed in Herpes infection and NMDAR encephalitis. Finally, it describes in detail the neuropsychological symptoms and cognitive functions during disease flare and recovery. [ABSTRACT FROM AUTHOR]