Perinatal brain trauma, including hypoxic-ischemic encephalopathy and mechanical injury during pregnancy, labor, or delivery, represents an early-acquired brain injury that disrupts the identical subcortical, brainstem, cerebellar, and emerging cortical visual, oculomotor, and vestibulo-ocular pathways commonly impaired in mild traumatic brain injury (mTBI) or concussion. This topical review examines five key neonatal reflexes: optomotor (optokinetic nystagmus [OKN], head-turning, fix-and-follow), oculomotor (reflexive saccades, doll's eye), vestibulo-ocular (VOR), pupillary light (PLR including relative afferent pupillary defect and alpha-omega pupil), and protective blink reflexes, as rapid, non-invasive biomarkers of pathway integrity in newborns. These hardwired reflexes, robust at birth but cortically refined by 3-6 months, are highly vulnerable to perinatal trauma; their absence, asymmetry, or failure to mature signals risk for cortical visual impairment and gaze instability that mirror post-concussion symptoms. We highlight syndromic red-flag clusters, behavioral state considerations for testing, and immediate infant-adapted visual rehabilitation strategies (fixation/pursuit training, OKN stimulation, vestibular exercises) during the critical 0- to 6-month sensitive period. By linking neonatal reflex assessment to mTBI rehabilitation frameworks, this review supports proactive, life span-oriented intervention in pediatric neurology and neuro-optometry/ophthalmology.
This systematic review and meta-analysis aims to synthesize evidence on the safety and efficacy of brivaracetam (BRV) usage in pediatric epilepsy. The primary outcome of our study was to assess the endurability of BRV in a population of children (age ≤18 years) with epilepsy, which was measured by the retention rate. The responder rate, rate of seizure freedom, rate of adverse effects, and rate of withdrawal from the study were all taken as secondary outcomes, with a total number of 12 citations included in our meta-analysis. Pooled estimation gave us a retention rate of 66%, a responder rate of 35%, and a pooled seizure freedom rate of 13%. When analyzing adverse events data, 25% of patients experienced treatment emergent adverse events, whereas 9% experienced behavioral adverse events. This study reports that BRV is safe and effective in a pediatric population. These findings warrant the necessity for further studies in BRV effectiveness, with specificity toward different classifications of epilepsy, ideal dosages for beneficence, and larger trials.
In complex neurodevelopmental disorders such as Lennox-Gastaut syndrome (LGS), treatable metabolic comorbidities may be masked by the severity of the primary phenotype. We report an 8-year-old boy with LGS and bilateral polymicrogyria whose underlying Imerslund-Gräsbeck syndrome was unmasked following a palliative Gamma Knife corpus callosotomy. Although the patient underwent Gamma Knife corpus callosotomy, his seizures remained uncontrolled. Consequently, vagus nerve stimulator implantation was planned; however, severe anemia (hemoglobin: 3.3 g/dL) was detected on admission for the procedure. Initially, the hematologic abnormalities were attributed to polypharmacy, prompting a dose reduction in antiepileptic medications. A concurrent anemia workup revealed vitamin B12 deficiency, and intramuscular B12 replacement therapy was initiated. However, because the macrocytic anemia was unexpectedly severe and other hematopoietic lineages remained unaffected, advanced investigations were performed. Genetic analysis revealed compound heterozygous missense variants in the CUBN gene. Following parenteral vitamin B12 replacement, the patient achieved not only hematologic recovery but also a remarkable reduction in seizure frequency over the subsequent 9 months. This case illustrates diagnostic overshadowing and underscores the necessity of considering comprehensive genetic and metabolic testing in refractory epilepsy, as addressing a metabolic second hit can significantly optimize neurologic outcomes.
Charcot-Marie-Tooth disease (CMT) comprises a heterogeneous group of inherited peripheral neuropathies with onset often in childhood. Activity-limiting fatigue is a common symptom of many neuromuscular disorders. The aim of this study was to explore the experience of activity-limiting fatigue among children with CMT and evaluate the utility of the generic Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS). Fifteen individuals aged 8-18 years with CMT and 12 parents participated in this study. Participants completed the PedsQL-MFS, and focus group interviews were conducted to gather feedback about the PedsQL-MFS and gain in-depth insights about their experiences of activity-limiting fatigue and impact on quality of life. Children with CMT and their parent-proxy reported significantly lower PedsQL-MFS fatigue scores (indicating greater fatigue) in comparison to normative values (P < .01), which, however, was deemed limited in scope to measure the full experience of fatigue in CMT. During in-depth interviews, 8 domains emerged as important considerations for assessing fatigue in CMT, including impact of fatigue on motor function, impact of fatigue on endurance and performance, recovery from physical activities, location of fatigue, muscle fatigue, timing of fatigue, impact of fatigue on behavior, and relationship to nutrition and hydration. These 8 domains may inform development of a disease-specific patient- and parent-reported outcome measure of fatigue.
Menke-Hennekam syndrome types 1 and 2 (MKHK1 and MKHK2) are autosomal dominant neurodevelopmental disorders characterized by psychomotor developmental delay, intellectual disability, and dysmorphic features. MKHK1 is caused by heterozygous variants in exons 30-31 of the CREBBP gene, whereas MKHK2 results from heterozygous variants in EP300. Although these genes are classically associated with Rubinstein-Taybi syndrome (RTS), Menke-Hennekam syndrome presents a distinct phenotype despite involvement of the same alleles. We report 2 patients who exhibited developmental delay, intellectual disability, and dysmorphic features without typical RTS findings. Genetic analysis revealed a novel frameshift variant in EP300 in one patient and a de novo missense variant in CREBBP in the other. Long-term follow-up and increasing use of whole-exome sequencing have facilitated recognition of Menke-Hennekam syndrome as a distinct clinical entity. Reporting 2 patients with exon 31 variants in CREBBP and EP300, we aim to improve awareness and diagnostic accuracy of this rare disorder.
TANGO2 deficiency disorder is a rare, autosomal recessive, neurometabolic condition typically characterized by recurrent metabolic crises, rhabdomyolysis, cardiac arrhythmias, and neurodegeneration. We report a 5-year-old boy with normal early development followed by fever-triggered metabolic encephalopathy from 10 months, associated with severe high anion-gap metabolic acidosis. He subsequently developed epileptic spasms with hypsarrhythmia, evolving into refractory epilepsy and profound developmental impairment. Serial neuroimaging showed early cortical diffusion restriction followed by progressive cerebral atrophy. Notably, classical features such as rhabdomyolysis, cardiac involvement, and TANGO2 spells were absent, and metabolic evaluation was largely unremarkable between episodes. Genetic analysis identified a homozygous 3.6-kb deletion involving exons 4 to 6 of the TANGO2 gene. This case highlights that TANGO2 deficiency may present predominantly as a developmental and epileptic encephalopathy phenotype and is more commonly due to multi-exon deletions rather than single-nucleotide variations as seen in other inherited metabolic disorders. Early genetic testing, including copy number analysis, is essential for diagnosis and management.
BackgroundKaya-Barakat-Masson syndrome (KABAMAS) is a recently described autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in YIF1B, a gene crucial for trafficking between the endoplasmic reticulum and the Golgi apparatus. Disruption of this pathway leads to Golgi disorganization and neuronal dysfunction, resulting in severe developmental delay, visual impairment, and progressive spasticity.Case PresentationWe report an 11-month-old Turkish girl with profound developmental delay, absent head control, poor feeding, laryngomalacia and cortical visual impairment. Brain magnetic resonance imaging (MRI) revealed corpus callosum thinning and mild ventriculomegaly. Comprehensive metabolic investigations were unrevealing. Whole exome sequencing analysis identified a novel homozygous YIF1B frameshift variant, c.440_441delinsA (p.Ala147Aspfs*51), predicted to cause loss of function.ConclusionThis case broadens the mutational spectrum of YIF1B-related disease and highlights the distinctive clinical pattern of KABAMAS. Recognition of the combination of developmental delay, cortical visual loss, and normal metabolic studies should prompt early genetic analysis. Timely molecular diagnosis enables accurate counseling and multidisciplinary management for affected families.
Most seizures in children with epilepsy occur outside the neurology clinic. Seizure action plans (SAPs) are designed to extend the neurologist's management plan into these settings. Early SAPs primarily targeted caregivers, while current plans target not only caregivers but also teachers, other medical providers, and anyone else who may be able to intervene on behalf of these children. Some studies suggest that SAPs can improve caregiver knowledge, comfort, and confidence with rescue medication administration. However, evidence that SAPs reduce emergency department use or affect other downstream outcomes is less consistent. This topical review summarizes evidence from the past decade on pediatric SAPs across home, school, emergency medical services, emergency departments, primary care, and residential or long-term care settings.
BackgroundTANGO2-related disorder (TDD) is a rare autosomal recessive condition characterized by episodic metabolic crises, rhabdomyolysis, encephalopathy, and life-threatening cardiac arrhythmias, with marked phenotypic variability that often contributes to delayed diagnosis.Case presentationWe report 2 sisters homozygous for the recurrent TANGO2 variant c.460G>A (p.Gly154Arg), identified in a family of Hispanic/Latino ancestry, who exhibited divergent clinical presentations. The older sibling presented with developmental delay and recurrent fasting-induced hypoglycemia associated with hyperCKemia and episodic weakness, whereas the younger sibling showed early hypotonia, ataxia, behavioral dysregulation, and subclinical hypothyroidism without initial metabolic crises. Brain magnetic resonance imaging studies were normal in both patients. In both cases, routine metabolic testing was largely unremarkable between episodes, and early manifestations were interpreted within isolated subspecialty frameworks, delaying diagnostic integration.ConclusionThese cases highlight intrafamilial variability within the recognized TDD spectrum and underscore the importance of early recognition of neurologic and endocrine features as potential red flags. Prompt molecular diagnosis is essential to guide anticipatory management and reduce morbidity and mortality.
Caregivers frequently turn to social media for pediatric seizure guidance, yet it remains unclear whether high-reach content aligns with established first-aid recommendations. We conducted a cross-sectional analysis of 150 high-view seizure-related videos across TikTok, Instagram, and YouTube (50 per platform). Videos were coded for creator type, accuracy, emergency department (ED)/911 guidance, and Global Quality Score (0-5). Overall accuracy was high (88.7%); however, only 49.3% included ED/911 guidance. Educational quality differed by creator type (F = 6.15, P < .001), with Health Care Professional videos demonstrating higher Global Quality Scores than Parent/Caregiver and Influencer content. Parent/Caregiver videos achieved the highest mean views (2.88 million), although median engagement was substantially lower than that of Health Care Professional and Health Organization videos, indicating that the higher mean reach was driven by a small number of viral caregiver posts rather than consistently higher engagement. Accuracy and quality were not independently associated with views. These findings suggest that engagement dynamics, rather than educational completeness, drive reach, underscoring the importance of clinician presence in digital seizure education.
Cognitive and developmental neuroscience in Nigeria faces a range of challenges, including limited research infrastructure, insufficient awareness, and cultural barriers that hinder early diagnosis and intervention for neurodevelopmental disorders (NDDs). Despite these obstacles, significant progress has been made through collaborations with international organizations such as the International Brain Research Organization-Africa Regional Committee (IBRO-ARC), International Society for Neurochemistry (ISN), and The World Academy of Sciences (TWAS), which have provided crucial funding and mentorship to Nigerian neuroscientists. These partnerships have enabled access to advanced research methodologies and fostered knowledge exchange within the African context, particularly through initiatives like the African Brain and Cognitive Development Network (AfriBCD). The impact of maternal and childhood infections, including malaria and congenital viruses, on neurodevelopment highlights the need for targeted public health measures. This article reviews the current state of cognitive and developmental neuroscience in Nigeria, focusing on ongoing research efforts, key challenges, and opportunities for future growth. Strengthening local capacity, expanding sustainable funding opportunities, and facilitating the translation of research into clinical practice are critical steps toward improving the management of neurodevelopmental disorders (NDDs) in Nigeria and enhancing long-term neurodevelopmental outcomes.
BackgroundAttention deficit hyperactivity disorder (ADHD) in children is a common neuropsychiatric disease in the world, which has a significant impact on children, families, and society.AimsThis study aims to examine the trends in ADHD incidence, prevalence, and disability-adjusted life years (DALYs) among children to guide preventive measures.MethodThis cross-sectional analysis used data from the Global Burden of Diseases (GBD) spanning 1990 to 2021 across 204 nations and territories. Children diagnosed with ADHD aged ≤14 years were incorporated into the analysis. The main outcome measures include incidence, prevalence, DALYs, case changes, and estimated annual percentage changes (EAPCs). The trends were categorized by location, nation, age, sex, and Socio-Demographic Index (SDI). Meanwhile, an age-period-cohort (APC) model is used to estimate net drifts, local drifts, longitudinal age curves, and the period relative risks. Bayesian APC (BAPC) models were used to anticipate the global burden of ADHD from 2022 to 2051. Data were analyzed from September 10, 2024, to September 25, 2024.ResultsA total of 33 429 324 children (73.14% male; 26.86% female) were included in the analysis. There were 4 111 621 children with ADHD cases globally in 2021. From 1990 to 2021, pediatric ADHD cases rose 9.92% (95% uncertainty interval [UI], 7.13%-13.16%). Over the past 32 years, the global incidence rate decreased from 215.08 (95% UI, 146.23-314.58) to 204.37 (95% UI, 137.94-295.99), whereas prevalent cases increased from 29 564 63 to 33 429 32. DALYs increased from 362 607 to 410 706, with the middle-SDI region having the highest incidence and DALY rate in 2021. Incidence increased most in Western Europe (EAPC, 0.50%), whereas prevalence increased most rapidly in South Asia (EAPC, 0.33%). In 2021, Australia had the highest national incidence (638.35), prevalence (5295.68), and DALYs (65.13) among 204 nations. High-SDI regions had the highest net drift in both incidence rate and prevalence rate (0.21% for each). APC analysis showed that the burden of ADHD exhibited significant age, period, and cohort dependencies, with notable sex and regional heterogeneity. Incidence and prevalence were significantly higher in males than females, although the gender gap has recently narrowed (eg, incidence rate ratio in 2019.5: male 0.97, female 0.96). Furthermore, incidence rates in high-SDI regions worsened over time and across birth cohorts. BAPC model predicts that ADHD incidence will continue to rise, reaching 247.68 incidence rate by 2051 and 4 468 925 incident cases. The number of prevalent cases is projected to reach 25 357 194, and the DALY rate will rise to 23.93.ConclusionsChildhood ADHD represents a growing global public health challenge, with projected increases in incidence, prevalence, and DALYs, particularly in high-middle-SDI regions. Concurrently, DALY rates are rising most rapidly in low-SDI areas. Enhanced understanding of the epidemiology of childhood ADHD may inform targeted prevention and management strategies.
ObjectiveThis study aimed to evaluate the frequency of school absenteeism and associated clinical, sociodemographic, and psychosocial factors in children, adolescents diagnosed with migraine.MethodsThis cross-sectional, descriptive study included 70 pediatric migraine patients (aged 12-17 years; mean age: 14.8 ± 1.3 years) followed at Necmettin Erbakan University Pediatric Neurology Outpatient Clinic. Participants were diagnosed according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3) criteria. Data were collected via a structured 12-item questionnaire covering demographic characteristics, clinical migraine features, school absenteeism duration, academic impact, parental work loss, and teacher awareness. Statistical analyses included χ2, Mann-Whitney U, and multivariate logistic regression tests.ResultsThe majority of patients were female (62.9%) and in high school (82.9%). Migraine without aura was the predominant subtype (91.4%). The mean school absenteeism over the preceding year was 4.3 ± 2.4 days. Patients with frequent attacks (>1/mo) had significantly longer absenteeism compared with infrequent attackers (5.1 vs 3.3 days; P = .001). Academic decline was reported by 11.4% of patients and was associated with significantly higher absenteeism (7.4 vs 3.9 days; P = .001). Only 22.9% of patients received prophylactic treatment. Parental work loss was universal (100%; mean 2.5 ± 1.1 days). Teacher awareness of migraine diagnosis was absent in all cases (0%).ConclusionMigraine imposes a significant multidimensional burden on children's educational life, with attack frequency being the primary driver of absenteeism. The complete lack of teacher awareness and high rates of parental work loss underscore critical deficiencies in school-health care collaboration. Multidisciplinary strategies integrating optimized prophylaxis, school-based awareness programs, and individualized health plans are urgently needed.
Progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is a rare neurodegenerative disorder caused by pathogenic variants in NAXE gene. Movement disorders are among the clinical features of PEBEL1; however, no case presenting with paroxysmal exercise-induced dyskinesia (PED) has been reported. We reported the case of a 14-year-old girl who presented with PED episodes. Six months after the onset of episodes, she developed encephalopathy and focal status epilepticus. Exome sequencing analysis identified a homozygous pathogenic variant in NAXE gene, and she was diagnosed with PEBEL1. She was started on mitochondrial cocktail and multiple antiseizure medications; however, no response was observed. With the ketogenic diet (KD), seizure control was achieved and improvement in cognitive functions was observed. PED is a clinical feature not previously reported in PEBEL1 cases, and our case expands the phenotypic spectrum of this disorder. Additionally, our case highlights that KD may be a treatment option in PEBEL1.
Background Recurrent herpes simplex virus type 1 (HSV-1) encephalitis in children is rare, and its pathophysiology remains incompletely understood. Both viral reactivation and host immune dysregulation have been implicated. Advances in metagenomic next-generation sequencing (mNGS) and immune profiling provide new opportunities to elucidate disease mechanisms. Case Presentation: We detail a 13-year-old boy of Qiang ethnicity who experienced 3 neurologic episodes, including 2 virologically confirmed HSV-1 encephalitis events over 7 years. The third recurrence involved fever, seizures, and progressive bilateral temporal lobe lesions visible on magnetic resonance imaging. Cerebrospinal fluid (CSF) mNGS confirmed HSV-1 reactivation, and viral genomic sequencing demonstrated a highly conserved viral genome without high-confidence nonsynonymous mutations. Immune profiling showed compartmentalized central nervous system inflammation with elevated CSF cytokines (interleukin [IL]-6, IL-8, IL-10, interferon [IFN]-α, IFN-γ) and altered lymphocyte subsets, despite normal serum results. The patient was treated with acyclovir, intravenous immunoglobulin, and low-dose corticosteroids, which controlled seizures but left persistent neurocognitive deficits. Multidisciplinary follow-up is crucial to mitigate long-term neurocognitive sequelae. Literature Review: We reviewed 10 previously published pediatric cases of recurrent HSV-1 encephalitis, which demonstrated heterogeneous recurrence intervals, contralateral or novel lesion involvement, and frequent cognitive sequelae. Few studies integrated viral genomics or immune profiling. Conclusions The findings suggest that recurrent pediatric HSV-1 encephalitis may be driven by viral reactivation in the context of CNS-restricted immune dysregulation, rather than reinfection or viral evolution.
