Journal of Child Neurology最新文献

The objective of this prospective cohort study was to explore parents' perspectives of patients' experiences of the first available novel disease-modifying therapy for SMA in Sweden. Patients with SMA and their parents/legal guardians were identified in the National Patient Register and the Multi-Generation Register. Data was recorded using an electronic questionnaire administered at baseline, and after 6, 12, and 18 months. In total, 47 parents to 33 children with SMA (mean patient age: 9 years, 59% female; 27% with SMA type I, 33% with type II, and 39% with type III) participated. All parents reported that they wished their child to be treated with nusinersen and most parents (81%) reported that they had sufficient information to make an informed treatment decision. Across follow-up, almost all parents reported having a positive experience of nusinersen. Our study provides unique insights into caregivers' real-world experiences of a novel disease-modifying therapy for SMA.

BackgroundHypoxic-ischemic encephalopathy is a serious neurologic condition caused by reduced blood and oxygen supply to the brain, typically occurring during birth. Mitochondria play a crucial role in the pathophysiological mechanisms of hypoxic-ischemic encephalopathy, yet a comprehensive bibliometric analysis of this research area is lacking. This study aims to identify research hotspots and trends related to mitochondria and hypoxic-ischemic encephalopathy through a detailed bibliometric analysis.MethodsWe searched the Web of Science Core Collection for studies on hypoxic-ischemic encephalopathy and mitochondria published between 2004 and 2024. Using VOSviewer, Citespace, and the R package "bibliometrix," we conducted a comprehensive analysis to explore research trends, key topics, and collaborations.ResultsA total of 162 eligible articles were identified. The annual number of publications has increased over time, with peaks in recent years. The top contributing countries were China, the United States, and the United Kingdom, showing extensive international collaborations. Major institutions include Augusta University, Southern Medical University, and the University of the Basque Country. The leading journals were the International Journal of Molecular Sciences and Neurobiology of Disease. Keyword analysis highlighted neuroprotection, apoptosis, oxidative stress, and ferroptosis as primary research themes. Influential references with strong citation bursts were identified, indicating their impact on the field.ConclusionThis is the first bibliometric analysis of research on mitochondria and hypoxic-ischemic encephalopathy, highlighting key trends and hotspots. Our findings provide valuable insights into the development and direction of research in this field and emphasize the importance of mitochondria in understanding and potentially mitigating the impacts of hypoxic-ischemic encephalopathy.

BackgroundAutism spectrum disorder and epilepsy commonly occur together (ASD+EPI), suggesting shared pathology. However, epilepsy phenotypes within ASD+EPI are very heterogenous. Preterm birth poses a risk for both autism and epilepsy, and therefore may have a distinctive phenotype.MethodsWe used clinical EEG reports from more than 200 patients diagnosed with ASD+EPI and extracted lateralization and location data across multiple EEG time points. We analyzed epilepsy phenotypes between children born <32 weeks, 32-36⁺⁶, and 37-40⁺⁶ weeks to determine whether gestational age at birth impacts propensity for focal vs generalized epileptic activity.ResultsPatients with a history of birth before 32 weeks' gestational age had increased incidence of focal interictal activity compared with patients born after 32 weeks. There were no differences in seizure or interictal categorization between patients born moderately/late preterm and those born at term.ConclusionsThese results suggest that patients born extremely/very preterm who develop ASD+EPI have a predisposition toward focal epileptic activity, which may be due to changes in white matter development following very preterm birth.

ObjectivesMore than half of males with X-linked adrenoleukodystrophy (ALD) develop progressive, inflammatory cerebral demyelination (cerebral adrenoleukodystrophy). Treatment for cerebral adrenoleukodystrophy is limited with no standard therapies for advanced cerebral adrenoleukodystrophy. We reviewed cerebral adrenoleukodystrophy literature and expert opinion, compiling immunopathology, biomarkers, and therapies tested.MethodsWe reviewed published literature from January 1, 1970, through November 1, 2024, and surveyed expert clinicians worldwide caring for cerebral adrenoleukodystrophy patients for unpublished agent use.ResultsWe identified 20 publications with primary data on human cerebral adrenoleukodystrophy immunopathology. Seventeen publications reported cerebral adrenoleukodystrophy biomarkers. We identified 14 publications reporting use of 7 different agents; unpublished clinician reports identified use of 9 different agents.ConclusionsCerebral adrenoleukodystrophy immunopathology represents complex dysregulation of cytokines, macrophages, T cells, astrocytes, oligodendrocytes, and microglia. Partial responses to cerebral adrenoleukodystrophy were noted with intravenous immunoglobulin, sirolimus, leriglitazone, and mycophenolate. Our findings suggest consideration for a randomized platform trial of immunomodulatory agents for advanced cerebral adrenoleukodystrophy.

Rett syndrome is a neurodevelopmental disorder that primarily affects females and is often associated with sleep problems. To date, few studies have examined how sleep problems correspond to aspects of clinical severity in Rett syndrome. In this study, we examined how sleep architecture and sleep-disordered breathing correspond to psychometrically validated outcome measures that are being used in clinical trials. Thirteen participants (mean [M] = 5.96 years, standard deviation [SD] = 2.6), all with confirmed pathogenic variants in MECP2, were enrolled. Participants underwent polysomnography and formal clinical assessments. Six of thirteen participants had obstructive sleep apnea, which was worse during rapid eye movement (REM) sleep with associated hypoxemia and disruptions in sleep architecture. Decreased REM sleep time significantly correlated with higher overall clinical severity (r = -.57; P = .04), lower functional skills (r = -.56; P = .04), and lower social skills (r = -.57; P = .04) using the Revised Motor Behavioral Inventory. Results of t tests revealed that those with obstructive sleep apnea had significantly increased wake time. Those with obstructive sleep apnea also had more behavioral difficulties (higher anxiety, mood disturbance) as captured using the Rett Syndrome Behavior Questionnaire. Taken together, the results of this study show that reduced REM sleep is very common in Rett syndrome and is associated with more impairments in functional and social skills. Obstructive sleep apnea is also very common, and is associated with changes to sleep architecture, higher anxiety, and more mood disturbances. This suggests that providers should routinely screen for sleep problems and implement interventions that can positively impact the quality of life of individuals with Rett syndrome and their families.

Brucellosis is a zoonotic infection common in many parts of the world, but rare in the United States. This case report presents a unique instance of pediatric neurobrucellosis mimicking a brain tumor, marking the first reported case in the United States and only the fourth globally in the general population. Brucellosis is endemic to the Middle East, Indian subcontinent, South Africa, parts of South and Central America, and Mexico. The primary Brucella species causing human infection include Brucella melitensis (reservoir: sheep and goats), Brucella suis (swine), and Brucella abortus (cattle), with transmission primarily via unpasteurized dairy, direct animal contact, or inhalation of aerosols.¹ Neurobrucellosis, a rare complication, manifests in diverse ways, including meningitis, encephalitis, cranial neuropathies, intracranial hypertension, and psychiatric symptoms. Its clinical variability often leads to diagnostic delays and complications. Early recognition and treatment require a high index of suspicion to mitigate its potentially severe outcomes.² This case underscores the importance of considering neurobrucellosis in atypical neurologic presentations.

Pathogenic variants in the HADHA and HADHB genes are associated with impairment of mitochondrial trifunctional protein. Mitochondrial trifunctional protein deficiency is a disorder of long-chain fatty acid oxidation with different clinical presentations: the neonatal-onset form expressing with severe cardiac phenotype, the infantile-onset form with intermediate hepatic phenotype with metabolic crises, and the late-onset form with mild neuromyopathic phenotype. Long-term complications in patients with the intermediate and late-onset phenotypes include peripheral neuropathy and retinopathy. We report a patient harboring 2 compound heterozygous variants in the HADHA gene (p.Tyr724* and p.Gly319Ser) and presenting with an early-onset, progressive sensorimotor axonal polyneuropathy, without any other systemic manifestations typical of mitochondrial trifunctional protein deficiency. We also provide a literature review of HADHA mutated patients presenting with early-onset isolated neuropathy phenotype.

Wernicke encephalopathy is most commonly associated with alcohol consumption and in patients with malnutrition. This case report discusses a rare presentation in an adolescent due to avoidant restrictive food intake disorder following COVID-19 infection. We performed a review of the literature and compiled reported cases of pediatric Wernicke encephalopathy.

BackgroundMany individuals with chronic tic disorders endorse sensory dysregulation. Whether sensory dysregulation is linked with co-occurring conditions or associated with greater tic severity, urge severity, or severity of co-occurring conditions in this population is unknown. Characterizing sensory dysregulation in chronic tic disorders may help illustrate the mechanisms underlying development of chronic tic disorders.MethodsWe enrolled 40 subjects ages 6 to 17 with chronic tic disorders. Sensory profiles were determined by the parent-proxy reported Short Sensory Profile 2 or the self-reported Adolescent/Adult Sensory Profile. Symptom severities for anxiety, tics, obsessive-compulsive disorder, attention-deficit hyperactivity disorder (ADHD), and premonitory urge were assessed. Anxiety disorder diagnoses were determined using the Anxiety and Related Disorders-IV Child and Parent Interview. Obsessive-compulsive disorder and ADHD diagnoses were determined by clinician interview. Relationships between abnormal sensory profiles and co-occurring conditions were assessed with the Fisher exact test. Relationships between sensory profiles and continuous variables were assessed using Student 2-sided t test and linear regression.ResultsGreater total sensory profile scores in youth with chronic tic disorders were associated with worse tic (P = .001) and premonitory urge severities (P = .002). Participants with abnormal sensory avoidance and sensitivity had greater obsessive-compulsive disorder (avoidance: P < .001; sensitivity: P = .002), ADHD (avoidance: P = .01; sensitivity: P < .001), and anxiety (Screen for Child Anxiety-Related Emotional Disorders [SCARED]-Parent avoidance: P = .009; SCARED-Parent sensitivity: P = .01; SCARED-Child avoidance: P = .004; SCARED-Child sensitivity: P < .001) symptom severity compared with participants with normal sensory avoidance and sensitivity.ConclusionSensory dysregulation, specifically abnormal sensory avoidance and sensory sensitivity, is common in youth with chronic tic disorders and associated with increased severity of chronic tic disorders-related symptoms and co-occurring conditions.