Pediatric Neurology[JOURNAL]
Sun
200 papers
The Effects of Backward Downhill Treadmill Training Following Botulinum Toxin-A Injection and Serial Casting in Children With Cerebral Palsy: A Randomized Controlled Trial.
Atalan Efkere P, Akkaya HE, Uzun Akkaya K … +3 more , Çelik Hİ, Yildiz C, Elbasan B
Pediatr Neurol · 2026 May · PMID 42229287 · Publisher ↗
BACKGROUND: To investigate the effects of Backward Downhill Treadmill Training (BDTT) and structured physiotherapy (SP) following botulinum toxin-A (BoNT-A) injection and serial casting in children with cerebral palsy (C...
BACKGROUND: To investigate the effects of Backward Downhill Treadmill Training (BDTT) and structured physiotherapy (SP) following botulinum toxin-A (BoNT-A) injection and serial casting in children with cerebral palsy (CP). METHODS: The study included 17 children with CP, aged 5-10 years, who had been injected with BoNT-A into the medial gastrocnemius muscles and then followed by a serial casting protocol. Exercises including functional strengthening and stretching were applied to the children in the SP group (n = 9). The BDTT + SP group engaged in BDTT sessions in addition to SP training 3 days a week, for 6 weeks, and for 15 minutes each session. Muscle strength, range of motion, spasticity, selective motor control, gait, morphology of the gastrocnemius muscle, and activities of daily living were evaluated before and after the training. The effectiveness of the BDTT + SP programs together and SP program only was compared using Quade analysis of covariance test. RESULTS: The ankle dorsiflexor muscle strength, the range of motion for dorsiflexion and hip flexion, the dynamic catch response of spasticity, and the morphological aspects of the medial gastrocnemius muscle demonstrated improvement following both BDTT + SP and SP training alone. The BDTT + SP group exhibited greater improvements in several key parameters, including strength of plantar flexors and hip abductors, gait scores, vascularization, and stiffness of the medial gastrocnemius muscle, when compared to the group taking the SP program only. CONCLUSIONS: BDTT, in addition to SP, was associated with greater improvements in strength and vascularization of the BoNT-A-injected muscle in children with CP compared with SP alone.
Clinical Response and Serum Concentrations in Low-Dose Lacosamide Monotherapy for Children With Paroxysmal Kinesigenic Dyskinesia.
Tahara M, Matsuura R, Hirata Y … +5 more , Oba A, Horita H, Daida A, Koichihara R, Kikuchi K
Pediatr Neurol · 2026 May · PMID 42229286 · Publisher ↗
BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief, movement-triggered attacks. Voltage-gated sodium channel-blocking antiseizure medications, such as carbamazepine, although commonly used to t...
BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief, movement-triggered attacks. Voltage-gated sodium channel-blocking antiseizure medications, such as carbamazepine, although commonly used to treat PKD, have limitations in children due to enzyme induction and adverse effects. Lacosamide (LCM) enhances the slow inactivation of voltage-gated sodium channels; however, its efficacy and tolerability are unknown in children with PKD. Therefore, this study evaluated the clinical course of low-dose LCM monotherapy and associated serum concentrations for PKD. METHODS: We retrospectively reviewed records of five patients with PKD treated with LCM monotherapy at Saitama Children's Medical Center between August 2016 and July 2025. Data included age at LCM initiation, pretreatment attack frequency, LCM dose, serum LCM concentrations, treatment response, and adverse events. The primary outcome was the duration to attack remission or reduction, evaluated at 6 months. RESULTS: The median age at LCM initiation was 13.9 (range, 11.4-15.4) years. Attack frequency before treatment was ≥10, 5-10, and 1-5 episodes/day in two, two, and one patient, respectively. The median initial and maintenance doses were 2.0 and 1.9 mg/kg/day, respectively. Attacks disappeared within 2 days in four patients and decreased by 80% within 6 days in one. All patients achieved complete remission by 6 months. In all patients, attacks recurred after discontinuation but resolved within one day of treatment resumption. Serum LCM trough concentrations during maintenance therapy were 1.1-4.1 μg/mL. No adverse events were documented. CONCLUSIONS: Low-dose LCM monotherapy was associated with rapid control of PKD and remission at low serum concentrations, suggesting its clinical potential.
Impaired Brain Growth in Children Perinatally Infected With Chikungunya.
Sarton R, Medina-Santos R, Boumahni B … +6 more , Gauthier P, Renouil M, Medjane S, Bintner M, Zagury JF, Gérardin P
Pediatr Neurol · 2026 May · PMID 42224921 · Publisher ↗
BACKGROUND: Chikungunya neonatal encephalitis can cause microcephaly. However, little is known about brain growth following chikungunya perinatal infection. We sought to evaluate and explore head growth (HG) outcomes aft...
BACKGROUND: Chikungunya neonatal encephalitis can cause microcephaly. However, little is known about brain growth following chikungunya perinatal infection. We sought to evaluate and explore head growth (HG) outcomes after perinatal infection with the chikungunya virus. METHODS: In a child cohort, we compared at adolescence age HG, a proxy indicator of brain growth, and HG dynamics by infectious status. In an adult cohort, we searched for differentially expressed genes (DEGs) known to be related to subcortical brain volumes and head size to generate mechanistic hypotheses that could underly the relationship between chikungunya perinatal infection and brain growth. RESULTS: Cohort 1. Forty-two adolescent children (6 encephalitic, 13 nonencephalitic, 23 noninfected [NI]) were enrolled between January 2020 and January 2021. Head circumference was lower in infected than in NI children regardless of chikungunya presentation. HG showed a loss of percentiles in infected children, and a growth gain in the NI. This observation persisted when we compared nonencephalitic/nonmicrocephalic to NI children after excluding the six encephalitic children. Cohort 2. In the adult cohort, we identified 22 DEGs related to delayed myelination, postnatal microcephaly, hypomyelination, and leukoencephalopathy in the bulk transcriptome of peripheral blood mononuclear cells from 224 infected subjects recruited between August 2018 and October 2020. The relevance of these DEGs for neurologic involvement in chronic chikungunya was supported through pathway analysis. CONCLUSIONS: These findings could support the monitoring of neurocognitive milestones in all children perinatally infected with chikungunya and open up new avenues of research into the neuropathogenesis of chikungunya neonatal encephalitis.
Fatal Fat Embolism Syndrome Without Recognized Fracture in Patients With Duchenne Muscular Dystrophy: Two Case Reports.
Wade CA, Villa C, Goldstein LB … +6 more , Tian C, Zygmunt A, Rice K, Bagwell L, McGovern E, Toupin DN
Pediatr Neurol · 2026 May · PMID 42224920 · Publisher ↗
BACKGROUND: Fat embolism syndrome (FES) is an uncommon cause of sudden death in patients with Duchenne muscular dystrophy (DMD), typically following identifiable fractures. METHODS: We present two cases of sudden fatal F...
BACKGROUND: Fat embolism syndrome (FES) is an uncommon cause of sudden death in patients with Duchenne muscular dystrophy (DMD), typically following identifiable fractures. METHODS: We present two cases of sudden fatal FES in the setting of DMD without clinically recognized trauma or fracture. The first was a 7-year-old boy who had autism spectrum disorder and who also had sudden death after collapsing at home following a walk with no recognized trauma. The second was a 23-year-old man who developed sudden respiratory failure without preceding illness or injury that progressed to shock and subsequent death. RESULTS: Autopsy in both cases revealed extensive fat emboli in the microvasculature in multiple organs. CONCLUSIONS: These cases underscore the risk of FES in patients with DMD without apparent preceding injury.
Multi-Organ Dysfunction in Neonatal Hypoxic Ischemic Encephalopathy and Brain Magnetic Resonance Imaging Outcomes.
Jagadish S, Zimmerman MB, Glykys J
Pediatr Neurol · 2026 May · PMID 42224919 · Publisher ↗
BACKGROUND: Neonates with hypoxic-ischemic encephalopathy (HIE) often exhibit multi-organ dysfunction (MOD). We evaluated the association between MOD (defined as involvement of two or more organ systems) and HIE-related...
BACKGROUND: Neonates with hypoxic-ischemic encephalopathy (HIE) often exhibit multi-organ dysfunction (MOD). We evaluated the association between MOD (defined as involvement of two or more organ systems) and HIE-related brain magnetic resonance imaging (MRI) findings among neonates with neonatal encephalopathy who underwent therapeutic hypothermia. METHODS: Retrospective cohort study of all newborns admitted to the University of Iowa neonatal intensive care unit from January 1, 2008, to June 30, 2022, with encephalopathy who received therapeutic hypothermia. Neonates were classified as having normal or HIE-related changes on MRI. RESULTS: Of 222 newborns, 40% exhibited HIE-related MRI findings. MOD was observed in 56% of all patients. Respiratory issues occurred in 46% of neonates, hepatic and severe neurological dysfunction, defined as seizures or burst suppression in 40%, and cardiac dysfunction in 37%. Severe neonatal encephalopathy was more likely to be associated with MOD. Neonates with HIE changes on MRI were more likely to have MOD than those without (74% vs 45%, P < 0.0001). Neonates with four or more organ dysfunctions had a higher likelihood of abnormal brain MRI (odds ratio = 7.44; 95% confidence interval [CI] 3.51-15.76), and MOD was associated with a greater frequency of global injury on MRI. A logistic regression model showed that the odds ratio for having a brain MRI with HIE findings was 6.63 (95% CI 3.24-13.55, P < 0.0001) with severe neurological dysfunction and 1.95 (95% CI 0.96-3.97, P = 0.065) with cardiac dysfunction. CONCLUSIONS: A greater number of organ dysfunctions in neonates undergoing therapeutic hypothermia is associated with HIE-related changes on brain MRI. The highest risk is observed in patients with severe neurological or cardiac dysfunction.
DDX3X-Related Neurodevelopmental Disorder Presenting as a Cerebral Palsy Mimic.
Eroğlu A
Pediatr Neurol · 2026 May · PMID 42214842 · Publisher ↗
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Seizure Burden and Management in Infants With Hemimegalencephaly Prestaged and Poststaged Transarterial Embolization.
Buraniqi E, Gumayan RLF, Israel S … +7 more , Lowe CR, Landry C, Ruffini L, Kratimenos P, Pearl MS, Tsuchida T, Anwar T
Pediatr Neurol · 2026 May · PMID 42208165 · Publisher ↗
BACKGROUND: Hemimegalencephaly is characterized by unihemispheric hypertrophy, early-onset intractable epilepsy, and developmental delay. Staged transarterial embolization (TAE) was developed to reduce seizure burden in...
BACKGROUND: Hemimegalencephaly is characterized by unihemispheric hypertrophy, early-onset intractable epilepsy, and developmental delay. Staged transarterial embolization (TAE) was developed to reduce seizure burden in infants. This study characterizes the seizure profiles and management of infants treated with TAE. METHODS: Retrospective review of infants <3 months at Children's National Hospital from 2018 to 2023, including demographics, seizure profile, and medication management. RESULTS: Eight infants underwent TAE. The mean age of seizure onset was 9 (0-28) days old, and the average age of first embolization was 50 (13-99) days old. Four patients underwent three stages, three patients had four stages, and one patient had five stages. In the first week of seizure onset, 6 (75%) patients had focal impaired consciousness seizures with elementary motor phenomena and 3 (50%) developed epileptic spasms later. Additionally, 2 (25%) had focal impaired consciousness seizures with autonomic or cognitive phenomena. In the 24 hours before the first embolization, 6 (75%) patients had frequent recurrent electrographic seizures and one (17%) had frequent recurrent electroclinical seizures. At discharge, electrographic seizure freedom was achieved in 6 (75%) of patients, and rare electrographic-only seizures in 2 (25%) patients. One (13%) patient was seizure-free on the megalencephalic hemisphere but developed seizures on the contralateral hemisphere. Patients had a median of 8 antiseizure medications during admission but weaned to a median of 4 medications at discharge. CONCLUSIONS: All patients achieved complete resolution of electroclinical seizures from the affected hemisphere. Infants require escalation of antiseizure medications transiently, but after the final TAE, decreased to more typical epilepsy polytherapy.
Long-Term Mental Well-Being in Pediatric Traumatic Brain Injury Survivors: A Nationwide Longitudinal Study.
Kyösti E, Lindholm P, Mikkonen E … +5 more , Raj R, Ohtonen P, Peltoniemi O, Skrifvars MB, Ala-Kokko T
Pediatr Neurol · 2026 May · PMID 42208164 · Publisher ↗
BACKGROUND: The long-term mental and psychological sequelae of pediatric traumatic brain injury (TBI) are poorly studied, despite the potential for significant late-life impacts. This study investigates the long-term men...
BACKGROUND: The long-term mental and psychological sequelae of pediatric traumatic brain injury (TBI) are poorly studied, despite the potential for significant late-life impacts. This study investigates the long-term mental well-being of a national patient population of pediatric TBI survivors treated in intensive care. METHODS: This longitudinal follow-up study was conducted using a nationwide cohort based on a national intensive care unit registry and questionnaire survey. We used the Achenbach System of Empirically Based Assessment questionnaires to assess behavioral and emotional functioning 11 years after pediatric TBI treated in an intensive care unit. Additional questions addressed chronic diseases, need for therapy and medication, and socioeconomic status. RESULTS: There were 146 out of 337 (43%) responders to the Achenbach System of Empirically Based Assessment questionnaire. Out of the patients 24 (16%) had non-normal (clinical or borderline total score) scores. Psychiatric diagnoses (21% vs 3%, P = 0.008), need for therapy (33% vs 10%, P = 0.007), need for health care visits (96% vs 62%, P = 0.003), need for medication (58% vs 26%, P = 0.003), and chronic diagnoses (58% vs 31%, P = 0.020) were more prevalent in those with non-normal scores compared to those with normal scores. The proportion of females was higher among those with non-normal scores (63% vs 38%, P = 0.010). Females scored worse than males in several scales as follows: anxiety and depression (21% vs 8%, P = 0.025); withdrawal (18% vs 3%, P = 0.006); thought problems (23% vs 7%, P = 0.007); and externalizing behaviors (19% vs 7%, P = 0.032). Female sex was independently associated with one or more clinical or borderline (non-normal) scales in the Adult Self-Report or Youth Self-Report questionnaires (odds ratio 2.7; 95% confidence interval 1.2-6.2; P = 0.021) while injury severity or parental working status were not. CONCLUSIONS: The study highlights significant long-term mental health challenges in pediatric TBI survivors, particularly among females. These findings underscore the need for targeted mental health interventions and continuous monitoring of pediatric TBI patients into adulthood.
Methodological Quality of Clinical Practice Guidelines for the Diagnosis of Simple Febrile Seizures in Children: A Systematic Review Using the Appraisal of Guidelines for Research and Evaluation II Instrument.
Amer YS, Hamad M, Abukhaled M … +6 more , Otaif M, Al Shafi S, Al-Mehmadi S, Hundallah K, Bashiri F, Almuhaizea M
Pediatr Neurol · 2026 Apr · PMID 42202665 · Publisher ↗
BACKGROUND: Febrile seizures (FS) are common neurological events in children between 6 months and 5 years of age. Despite being benign and self-limiting, diagnostic variability persists across clinical practice guideline...
BACKGROUND: Febrile seizures (FS) are common neurological events in children between 6 months and 5 years of age. Despite being benign and self-limiting, diagnostic variability persists across clinical practice guidelines (CPGs). This systematic review aims to evaluate the quality of CPGs for diagnosis of simple FS using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) Instrument, offering insights to improve guideline development. METHODS: A search of bibliographic, CPG, and professional society databases was conducted for CPGs published between January 2011 and October 2025. Eligibility criteria included evidence-based CPGs available in English or Arabic, developed de novo, and targeting simple FS diagnosis in children. AGREE II was used by four appraisers to assess six CPG quality domains and two overall assessments. Discrepancies were resolved through focus group discussions. RESULTS: Out of 42 records retrieved, the following five CPGs met the eligibility criteria: American Academy of Pediatrics (2011), Japanese Society of Child Neurology (JSCN, 2015), Finnish Medical Association Duodecim and Finnish Pediatric Neurology Association (2020), Royal Children's Hospital Melbourne (2020), and American College of Radiology (ACR, 2021). The AGREE II standardized scores indicated variability in methodologic quality across CPGs, with the ACR and JSCN demonstrating higher rigor of development and clarity, while other CPGs scored lower in applicability and editorial independence. All CPGs consistently recommended supportive care, with limited use of diagnostics like electroencephalogram and neuroimaging. CONCLUSIONS: Substantial variability exists in the quality of FS CPGs. Enhancing guideline development with robust methodologies, improved implementation strategies, and greater transparency is essential to strengthen clinical utility and promote consistent, evidence-based practice.
Selective Episodic Memory Impairment in Pediatric Anti-Glutamic Acid Decarboxylase 65 Limbic Encephalitis With Relapsing Course.
Anand V, Vinayan KP, Sanji B … +2 more , Manoj PA, Radhakrishnan S
Pediatr Neurol · 2026 May · PMID 42190348 · Publisher ↗
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Understanding Misdiagnosis in Pediatric Epilepsy: A Prospective Analysis of Predictors and Patterns.
Patel M, Gupta MK, Saini L … +6 more , Kumar Mittal A, Gupta R, Dhanesh Goel A, Bhardwaj P, Sharma PP, Singh K
Pediatr Neurol · 2026 May · PMID 42190347 · Publisher ↗
BACKGROUND: The objective of this study was to determine the proportion of children misdiagnosed with epilepsy, to assess the diagnostic accuracy of the AIIMS modified INCLEN Diagnostic Tool for Epilepsy tool in a real-w...
BACKGROUND: The objective of this study was to determine the proportion of children misdiagnosed with epilepsy, to assess the diagnostic accuracy of the AIIMS modified INCLEN Diagnostic Tool for Epilepsy tool in a real-world tertiary setting cohort and to identify predictors of this condition. METHODS: From January to December 2024, a prospective study was carried out at a tertiary health care facility. Children who were referred to our tertiary center with a previous diagnosis of epilepsy or who were already taking anti-seizure medication, aged one month to 18 years, were recruited. Patients were evaluated with AIIMS modified INCLEN Diagnostic Tool for Epilepsy diagnostic tool and the diagnosis was validated by a pediatric neurologist. The diagnostic agreement was assessed using Cohen kappa and predictors of misdiagnosis were found using logistic regression. RESULTS: Among the 438 enrolled epilepsy patients, 53 (12.1%) patients were misdiagnosed as having epilepsy when events were nonepileptic in nature. On further evaluation, the most common actual diagnosis was migraine, followed by functional/dissociative seizures and movement disorders. There was substantial agreement between the tool and expert diagnosis. Age, father's occupation, and residential status were among the significant predictors. Using logistic regression, age (≥10 years) and urban residency were found to be independent predictors for misdiagnosis. CONCLUSIONS: Misdiagnosis in pediatric epilepsy is common. The study emphasized the importance of structured validated tools in improving accuracy while avoiding misdiagnosis in pediatric epilepsy. These findings highlight the importance of structured clinical assessment in improving diagnostic precision in pediatric epilepsy. Further research is required to assess the effectiveness of structured screening tools in primary and district-level health care settings.
Early Identification of Risk for Cerebral Palsy in a Cohort of Preterm Infants: Development of a Propensity Score Model Using Neonatal Risk Factors.
Scheidt M, Silveira RC, Procianoy RS … +1 more , Valentini NC
Pediatr Neurol · 2026 Jul · PMID 42184473 · Publisher ↗
BACKGROUND: To develop a preliminary propensity score model to predict cerebral palsy (CP) based on neonatal risk factors in preterm infants. METHODS: This case-control study included preterm infants followed for neurode...
BACKGROUND: To develop a preliminary propensity score model to predict cerebral palsy (CP) based on neonatal risk factors in preterm infants. METHODS: This case-control study included preterm infants followed for neurodevelopment and growth. Five controls were selected per case, totaling 108 participants (90 without CP and 18 with CP). Logistic regression was used to identify significant risk factors and estimate propensity scores. RESULTS: Of the 19 risk factors analyzed, 10 were significant; five were retained as independent predictors in the final model as follows: abnormal magnetic resonance imaging, seizures, peri-intraventricular hemorrhage, periventricular leukomalacia, and duration of invasive mechanical ventilation. The following two cutoff points were evaluated: 0.5 (50%), yielded 72.2% of sensitivity and 97.8% specificity, and 0.2 yielding higher sensitivity (83.3%) but lower specificity (91.1%) (20%). CONCLUSIONS: The model effectively discriminates CP risk in preterm infants. A higher cutoff (0.5) improves specificity and reduces false positives, whereas a lower cutoff (0.2) increases sensitivity and identifies more cases. Early identification may facilitate timely interventions and improve neurodevelopmental outcomes. Larger studies are needed to validate and refine the model.
Reduced Magnetic Resonance Imaging-Visible Perivascular Spaces in Neonatal Hypoxic-Ischemic Encephalopathy: A Combined Clinical-Imaging Model for Severity Prediction.
Dong X, He Y, Li J … +8 more , Liu M, Wu Y, Zhan C, Zhang H, Lin H, Jin K, Xiang Y, Zhuang X
Pediatr Neurol · 2026 Jul · PMID 42184472 · Publisher ↗
BACKGROUND: To evaluate magnetic resonance imaging (MRI)-visible perivascular spaces (PVSs) as an imaging marker of glymphatic function in neonatal hypoxic-ischemic encephalopathy (HIE) and to assess the diagnostic utili...
BACKGROUND: To evaluate magnetic resonance imaging (MRI)-visible perivascular spaces (PVSs) as an imaging marker of glymphatic function in neonatal hypoxic-ischemic encephalopathy (HIE) and to assess the diagnostic utility of a combined clinical-PVS model. METHODS: This retrospective study included 266 neonates with HIE, categorized as mild (n = 50) or moderate-to-severe (n = 216). PVS burden in the basal ganglia (BG) and white matter was assessed on T2-weighted imaging using visual grading and volumetric quantification. Logistic regression models (clinical vs combined clinical-PVS vs traditional MRI injury pattern model) were constructed, with performance evaluated by the area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis. RESULTS: A significant severity-dependent reduction in PVS metrics was observed in the BG. Neonates in the moderate-to-severe group exhibited significantly lower BG PVS fractions compared to the mild group (P < 0.001). Multivariate analysis identified BG PVS fraction and clinical indicators as independent predictors of severity. The combined clinical-PVS model achieved an AUC of 0.82, which was significantly higher than the AUC of 0.69 yielded by the traditional MRI injury pattern model (P < 0.05). CONCLUSIONS: HIE severity is characterized by a progressive reduction in BG PVS, suggesting a structural collapse of the glymphatic network in severe injury. The combined application of clinical markers and quantitative PVS metrics provides superior diagnostic accuracy compared to conventional MRI injury patterns. This objective approach complements clinical assessment and enhances risk stratification for neonates with HIE.
SLC6A1-Related Neurodevelopmental Disorder: A Scoping Review of Clinical Features and Emerging Therapeutic Strategies.
Samanta D
Pediatr Neurol · 2026 Jul · PMID 42173049 · Publisher ↗
BACKGROUND: Solute carrier family 6 member 1 (SLC6A1) gene encodes gamma-aminobutyric acid transporter 1 (GAT-1), the principal synaptic gamma-aminobutyric acid (GABA) transporter. Pathogenic heterozygous loss-of-functio...
BACKGROUND: Solute carrier family 6 member 1 (SLC6A1) gene encodes gamma-aminobutyric acid transporter 1 (GAT-1), the principal synaptic gamma-aminobutyric acid (GABA) transporter. Pathogenic heterozygous loss-of-function variants of SLC6A1 cause a developmental and epileptic encephalopathy characterized by early-onset epilepsy, intellectual disability, and autistic features. Despite a rapidly expanding translational pipeline, clinical evidence remains fragmented. This scoping review systematically maps the published evidence on the phenotypic spectrum and therapeutic landscape of SLC6A1-related neurodevelopmental disorder. METHODS: A systematic search of PubMed, Embase, OVID/MEDLINE, Web of Science, and ClinicalTrials.gov was conducted through March 2026, supplemented by hand-searching reference lists and American Epilepsy Society conference abstracts (2019-2025). The review was conducted per the Arksey and O'Malley framework and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. RESULTS: Epilepsy affects approximately 90% of clinically identified individuals, with seizure onset typically between 14 months and 5 years; predominant types include absence (60-72%), myoclonic-atonic (24-35%), and atonic seizures. Intellectual disability or developmental delay is present in 82-100% of patients, with cognitive impairment antedating seizure onset in over 60% of cases. Autistic features occur in 22-65% and hypotonia in 60-71%. Clinical severity correlates with degree of residual GAT-1 activity as follows: variants with near-total loss of GABA uptake (<10% residual function) are 4.6-fold enriched in severe phenotypes. Valproate remains the most consistently effective antiseizure medication, followed by lamotrigine, clobazam, and ethosuximide. Although levetiracetam is commonly used, behavioral adverse effects should be monitored. The ketogenic diet and acetazolamide represent evidence-supported adjunctive options. Among disease-modifying strategies, 4-phenylbutyrate restores GAT-1 trafficking in endoplasmic reticulum -retained variants and has demonstrated seizure reduction in 80% and seizure freedom in 40% of treated patients in the largest clinical cohort. Adeno-associated virus serotype 9-mediated gene replacement normalized electroencephalography abnormalities in preclinical models, with the first Phase I/II human trial (NCT07173153) dosing its initial patient in December 2025. CONCLUSIONS: As a severe developmental and epileptic encephalopathy, SLC6A1-related neurodevelopmental disorder is defined by a specific functional loss of GABA transport. This clear mechanistic substrate has allowed for the development of a highly focused translational pipeline, ranging from gene therapies to pharmacological chaperones. Critical gaps include the absence of prospective natural history data with standardized outcomes, lack of randomized controlled trials, and incomplete characterization of the adult phenotype. Prioritizing multinational registry-based cohort studies and validated disease-specific outcome measures is essential to support rigorous evaluation of transformative emerging therapies.
Risk Factors for Delirium in Pediatric Intensive Care Units: A Systematic Review and Meta-Analysis.
Zhang Z, Zhou P
Pediatr Neurol · 2026 Jul · PMID 42173048 · Publisher ↗
BACKGROUND: Delirium is a frequent and serious complication in critically ill children admitted in the pediatric intensive care units (PICUs). This systematic review and meta-analysis aimed to identify and quantify risk...
BACKGROUND: Delirium is a frequent and serious complication in critically ill children admitted in the pediatric intensive care units (PICUs). This systematic review and meta-analysis aimed to identify and quantify risk factors associated with delirium in the PICU. METHODS: Searches were conducted across PubMed, Embase, Web of Science, and Scopus from inception to November 9, 2025. Observational studies reporting delirium in PICU settings were included. Univariate odds ratios were pooled using DerSimonian-Laird random-effects models. RESULTS: Thirty-four studies were included. A total of 23 risk factors with at least five contributing studies were meta-analyzed. Significant predictors of delirium included younger age, developmental delay, neurological disorders, mechanical ventilation, prolonged ventilation, noninvasive ventilation, and multiple medication exposures, including benzodiazepines, opioids, dexmedetomidine, antiepileptics, and corticosteroids. Additional significant factors included vasoactive support, cyanotic heart disease, blood or component transfusion, physical restraints, and longer PICU stays. Sensitivity analyses showed robust findings for most predictors. Publication bias was minimal for most risk factors. CONCLUSIONS: Multiple modifiable and nonmodifiable risk factors contribute to delirium in critically ill children. The use of univariate data and high heterogeneity are important limitations that limit firm conclusions from the present evidence.
Diagnostic Complexity of Pediatric Hemophagocytic Lymphohistiocytosis With Central Nervous System Involvement.
Jang S, Kim HJ, Cha JH … +8 more , Kim J, Yoon H, Kim W, Choi JY, Kang HJ, Kim MJ, Kim SY, Chae JH
Pediatr Neurol · 2026 Jul · PMID 42173047 · Publisher ↗
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome frequently involving the central nervous system (CNS) and associated with poor outcomes. Neurological manifestations may precede or obs...
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome frequently involving the central nervous system (CNS) and associated with poor outcomes. Neurological manifestations may precede or obscure systemic features, resulting in diagnostic challenges. METHODS: We retrospectively reviewed pediatric patients with HLH treated at Seoul National University Children's Hospital between 2000 and 2024. CNS involvement was defined by neurological symptoms and abnormal cerebrospinal fluid (CSF) findings and/or brain imaging abnormalities. Clinical features, neuroimaging findings, CSF profiles, genetic testing results, treatment, and outcomes were analyzed. RESULTS: Among 136 screened patients with HLH, 20 met criteria for CNS involvement. Neurological symptoms were the initial manifestation in 6 of 20 patients (30%), and seizures were the most common symptom (14/20, 70%). Brain imaging abnormalities were observed in all patients who underwent neuroimaging (19/19), typically demonstrating multifocal parenchymal lesions with bilateral or multilobar involvement. CSF abnormalities were present in 13 of 18 patients (72%) but were nonspecific. More than half of the patients (11/20, 55%) were initially evaluated under alternative diagnostic considerations, contributing to delayed recognition of HLH. Genetic testing identified causative variants in 6 of 12 tested patients (50%), most commonly in UNC13D or STXBP2. Among the 19 patients with follow-up data, 7 (37%) survived. CONCLUSIONS: Pediatric HLH with CNS involvement shows heterogeneous and often misleading initial presentations. Neurological-predominant manifestations may contribute to delayed recognition of HLH. Careful longitudinal assessment and consideration of genetic evaluation may facilitate earlier diagnosis in selected patients.
A Randomized, Double-Blind, Pilot Study of N-Acetylcysteine for Motor and Cognitive Symptoms in Youth With Neurofibromatosis Type 1.
Gilbert DL, Aschbacher-Smith LE, Migneault KY … +6 more , Huddleston DA, Cecil KM, Beebe DW, Zhang B, Ratner N, Prada CE
Pediatr Neurol · 2026 Jul · PMID 42173046 · Publisher ↗
BACKGROUND: Children and youth with neurofibromatosis type 1 (NF1) commonly experience motor, behavioral, and cognitive problems. Promising findings from an NF1 mouse model suggested that the antioxidant N-acetylcysteine...
BACKGROUND: Children and youth with neurofibromatosis type 1 (NF1) commonly experience motor, behavioral, and cognitive problems. Promising findings from an NF1 mouse model suggested that the antioxidant N-acetylcysteine (NAC) might address underlying mechanistic deficits. METHODS: We conducted a 12-week (8-week treatment, 4-week washout), double-blind, placebo-controlled randomized trial of NAC in 8-16-year-olds with NF1. We screened 481 children, identified 203 eligible, and randomized 25; 23 received at least one dose (10 NAC at ∼70 mg/kg/day; 13 placebo). Outcomes were safety, tolerability, motor function (primary: Physical and Neurological Examination for Subtle Signs), cognitive function (secondary: attention deficit/hyperactivity disorder symptom scores and executive function measures), and exploratory biomarkers (transcranial magnetic stimulation and magnetic resonance spectroscopy measures). RESULTS: In the modified intention to treat analysis, no significant difference in Physical and Neurological Examination for Subtle Signs was observed between groups. In completer analyses, NAC did not improve any secondary or exploratory outcome at 8 weeks. NAC was generally well tolerated, although two participants were withdrawn by parents because of worsening behavior. Test-retest reliability of scales, measures, and biomarkers over 12 weeks was generally moderate. CONCLUSIONS: NAC was generally well tolerated but did not improve motor or behavioral outcomes in youth with NF1. Larger, longer trials with preceding dose-escalation and target-engagement studies are needed to evaluate new therapies.
Navigating Humanism in Pediatric Neurology: A Global Survey of Attitudes, Challenges, and Cultural Influences.
Mittal R, Sondhi V, Treat L … +1 more , Torres AR
Pediatr Neurol · 2026 Jul · PMID 42167046 · Publisher ↗
BACKGROUND: Humanism in medicine emphasizes the value of compassionate care and dignity in the face of illness. This principle-is central to child neurology, where physicians manage complex, lifelong conditions affecting...
BACKGROUND: Humanism in medicine emphasizes the value of compassionate care and dignity in the face of illness. This principle-is central to child neurology, where physicians manage complex, lifelong conditions affecting children and their families. However, little is known about how pediatric neurologists worldwide view and practice humanistic care. METHODS: A modified version of a validated humanism assessment tool was distributed to pediatric neurologists across diverse geographic and socioeconomic settings between February and May 2024. Self-reported responses (n = 155) were analyzed for agreement with humanistic principles and real-world application. Data were stratified by region, resource setting, age, experience, and employment type. RESULTS: Over 90% of respondents strongly agreed with core humanistic principles, including treating patients with dignity (143/153, 93.5%), respecting autonomy (144/153, 94.1%), and addressing emotional needs (143/153, 93.5%). However, marked variability in consistent application was observed. Only 99/153 (64.7%) "always" treated patients with dignity, and fewer than half reported consistently addressing emotional needs (64/151, 41.8%) or tailoring care to individuals (62/152, 40.8%). Physicians in high-resource settings more commonly reported adherence to these principles, though they also more frequently noted distractions that limited attentiveness. Age and experience correlated with stronger humanistic engagement, while younger physicians reported challenges with high-needs patients. Regional differences were observed in communication preferences and use of humor, reflecting cultural and systemic influences. CONCLUSIONS: Although pediatric neurologists endorse humanistic values, their application varies with context. Factors like structure, culture, and experience influence differences. This global overview of humanism in child neurology highlights the need for strategies to foster empathy, resilience, and connection.
Responsive Neurostimulation for Treatment of SCN1A-Associated Developmental and Epileptic Encephalopathies.
Philliben R, Willis E, Kim-McManus O … +3 more , Holder D, Policherla J, Espinoza AC
Pediatr Neurol · 2026 Jul · PMID 42167045 · Publisher ↗
BACKGROUND: Dravet syndrome and other SCN1A-associated epilepsies are developmental and epileptic encephalopathies with high seizure burden and frequent status epilepticus despite modern antiseizure therapies. Evidence f...
BACKGROUND: Dravet syndrome and other SCN1A-associated epilepsies are developmental and epileptic encephalopathies with high seizure burden and frequent status epilepticus despite modern antiseizure therapies. Evidence for responsive neurostimulation (RNS) in SCN1A-spectrum epilepsy remains limited. METHODS: We performed a multicenter retrospective clinical observation of six individuals with genetically confirmed SCN1A-spectrum epilepsy treated with RNS (five Dravet syndrome, one with genetic epilepsy with febrile seizures plus). RESULTS: Five patients underwent network-targeted bilateral thalamic depth lead implantation (four centromedian, one anterior nucleus) and one received frontal cortical strip leads based on individualized localization. Duration of activated stimulation ranged from 7 to 63 months. Seizure response at last follow-up was heterogeneous: one patient achieved >90% reduction, three achieved 50-90%, one achieved 1-49%, and one had no meaningful reduction (67% responders, ≥50% reduction). Notably, one patient had >9 months of seizure freedom and another had complete resolution of myoclonic-atonic seizures at most recent follow-up. Caregivers frequently reported improvements beyond seizure frequency, including reduced clusters/status epilepticus, decreased rescue and acute-care utilization, improved participation, and shorter postictal recovery. Patient 5 had stimulation-related paresthesia that resolved with reduction in stimulation frequency. Otherwise, no device- or stimulation-related complications were observed. CONCLUSIONS: These descriptive findings suggest that RNS, particularly thalamic targeting, may be a palliative consideration for select SCN1A-spectrum patients while underscoring variable benefit and the importance of multidimensional outcome assessments.
Descriptive Epidemiology of Pediatric Autoimmune Diseases of the Central Nervous System in the Afro-Descendant Population of the Caribbean Island of Martinique.
Tassin A, Lacofrette L, Gomez NG … +5 more , Bretonneau A, Signate A, Deiva K, Charollais A, Felix A
Pediatr Neurol · 2026 Jul · PMID 42167044 · Publisher ↗
BACKGROUND: The epidemiology of primary autoimmune diseases of the central nervous system is poorly described in Caribbean and Afro-descendant children. We studied the incidence, clinical and biological characteristics,...
BACKGROUND: The epidemiology of primary autoimmune diseases of the central nervous system is poorly described in Caribbean and Afro-descendant children. We studied the incidence, clinical and biological characteristics, immunological profiles, and prognosis of these diseases in Martinique. METHODS: We conducted a descriptive, retrospective, monocentric, population-based study from January 2010 to July 2024 including all children aged 0-17 years hospitalized for autoimmune encephalitis, multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein-associated disease (MOGAD) in the pediatric units of the Martinique University Hospital. The sequelae were assessed using an Expanded Disability Status Scale score. RESULTS: Twenty-five children were hospitalized for primary autoimmune disease of the CNS in Martinique and 16% were admitted to intensive care. The median age at onset was 14 years (2-17 years). The incidence rates found were 0.34 per 100,000 person-years (95% confidence interval 0.09-0.88) for NMOSD and 0.52 per 100,000 person-years (0.19-1.13) for MOGAD, and 0.60 per 100,000 person-years (0.24-1.24) for multiple sclerosis. The immunological profile of NMOSD/MOGAD was 70% seropositive (4 aquaporin-4 and 3 myelin oligodendrocyte glycoprotein). First-line treatment was high-dose corticosteroid therapy in most cases (88%). Long-term sequelae were rare in our population and mortality was null. CONCLUSIONS: Our study showed an increase in the incidence of NMOSD diseases compared to international studies and no significant difference in the incidence rates of the other autoimmune disorders of the CNS in children. Outcomes were comparable to European and North American countries in our population. The immunological profile showed a high proportion of anti-aquaporin-4 antibodies compared to the literature.
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