Search Results (38)

Background: Hypoxic–ischemic encephalopathy (HIE) is a leading cause of severe neurological impairments in childhood. Therapeutic hypothermia (TH) is both safe and effective in neonates born at ≥36 weeks gestation with moderate to severe HIE. We aimed to evaluate short-term outcomes—including brain injury detected on magnetic resonance imaging (MRI)—in infants born at 34–35 weeks of gestation drawing on our clinical experience with neonates under 36 weeks of gestational age (GA). Methods: In this retrospective cohort study, 20 preterm infants with a GA of 34 to 35 weeks and a matched cohort of 80 infants with a GA of ≥36 weeks who were diagnosed with moderate to severe HIE and underwent TH were included. Infants were matched in a 1:4 ratio based on the worst base deficit in blood gas and sex. Maternal and neonatal characteristics, brain MRI findings and short term outcomes were compared. Results: Infants with a GA of 34–35 weeks had a lower birth weight and a higher rate of caesarean delivery (both p < 0.001). Apgar scores, sex, intubation rate in delivery room, blood gas pH, base deficit and lactate were comparable between the groups. Compared to infants born at ≥36 weeks of GA, preterm neonates were more likely to receive inotropes, had a longer time to achieve full enteral feeding, and experienced a longer hospital stay. The mortality rate was 10% in the 34–35 weeks GA group. Neuroimaging revealed injury in 66.7% of infants born at 34–35 weeks of gestation and in 58.8% of those born at ≥36 weeks (p = 0.56). Injury was observed across multiple brain regions, with white matter being the most frequently affected in the 34–35 weeks GA group. Thalamic and cerebellar abnormal signal intensity or diffusion restriction, punctate white matter lesions, and diffusion restriction in the corpus callosum and optic radiations were more frequently detected in infants born at 34–35 weeks of gestation. Conclusions: Our study contributes to the growing body of literature suggesting that TH may be feasible and tolerated in late preterm infants. Larger randomized controlled trials focused on this vulnerable population are necessary to establish clear guidelines regarding the safety and efficacy of TH in late preterm infants. Full article

Smith–Lemli–Opitz syndrome (SLOS) is a rare, autosomal recessive genetic disorder caused by mutations in the DHCR7 gene, which encodes the enzyme responsible for the final step in cholesterol biosynthesis. Impaired enzyme function leads to cholesterol deficiency, affecting the development and function of the entire organism. The accumulation of cholesterol precursors enhances the formation of oxysterols, which are involved in the pathomechanism of neurological, ophthalmological, and vascular changes in patients. This review analyzes 53 studies published between 2020 and 2025 on the molecular mechanisms underlying the clinical features of SLOS, including cholesterol deficiency, oxysterol accumulation, and the latest diagnostic methods, including LC-MS/MS chromatography and biomarkers such as GFAP for monitoring disease progression. MRI is discussed as a supportive tool for neuroimaging, along with advances in prenatal diagnostics, such as the detection of cholesterol precursors in neonatal hair. Therapeutic options are also reviewed, with particular emphasis on cholesterol supplementation, cholic acid, and experimental treatments such as vitamin E supplementation, statin therapy, gene therapy, and liver transplantation. Current research indicates that expanding knowledge in this area not only improves patient prognosis but also provides hope for the development of effective therapies in the future. Full article

Prognostication of neurodevelopmental outcomes for neonates with hypoxic–ischemic encephalopathy (HIE) is primarily reliant on structural assessment using conventional brain magnetic resonance imaging in the clinical setting. Diffuse optical tomography (DOT) can provide complementary information on brain function at the bedside, further enhancing prognostic accuracy. The predictive accuracy and generalizability of DOT-based neuroimaging markers are unknown. This study aims to test the feasibility of prospectively recruiting and retaining neonates for 12 months in a larger study that investigates the prognostic utility of DOT-based biomarkers of HIE. The study will recruit 25 neonates with HIE over one year and follow them beyond NICU discharge at 6 and 12 months of age. Study subjects will undergo resting-state DOT measurement within 7 days of life for a 30–45-min period without sedation. A customized neonatal cap with 10 sources and eight detectors per side will be used to quantify cortical functional connectivity and to generate brain networks using MATLAB-based software (version 24.2). The Ages and Stages Questionnaires—3rd edition will be used for standardized developmental assessments at follow-up. This feasibility study will help refine the design and sample-size calculation for an adequately powered larger study that determines the clinical utility of DOT-based neuroimaging in perinatal brain injury. Full article

Introduction: Hyperbilirubinemia in newborns can lead to kernicterus, a severe form of neonatal encephalopathy caused by bilirubin toxicity. Despite timely interventions such as exchange transfusion, kernicterus can still develop, especially in high-risk infants. MRI is crucial for detecting early and evolving signs of bilirubin-induced brain damage. Case Report: We report a term newborn who developed severe hyperbilirubinemia and kernicterus despite receiving exchange transfusion. The infant presented on day 3 of life with jaundice, hypotonia, and feeding difficulties and had a bilirubin level of 51 mg/dL. After exchange transfusion, bilirubin levels normalized, but neurotoxicity persisted. Initial MRI at one month showed mild T1 hyperintensity in the hippocampi with no changes in the basal ganglia. At two months, T1 hyperintensities in the hippocampi partially resolved. By six months, MRI revealed T2 hyperintensities in the globus pallidus and hippocampal atrophy, consistent with kernicterus. Magnetic resonance spectroscopy (MRS) showed reduced N-acetylaspartate (NAA) levels, indicating neuronal loss. Discussion: MRI is essential in monitoring bilirubin-induced brain injury. In this case, early MRI findings showed mild hippocampal T1 hyperintensity, which resolved partially. At six months, T2 hyperintensities in the globus pallidus confirmed chronic bilirubin encephalopathy. MRS demonstrated a reduction in N-acetylaspartate, indicative of neuronal loss. Susceptibility-Weighted Imaging (SWI) showed no abnormalities, likely due to the myelination process in neonates. Conclusions: This case highlights the importance of repeated MRI in detecting bilirubin-induced brain damage. Early neuroimaging enables timely interventions and improves long-term neurodevelopmental outcomes in infants with severe hyperbilirubinemia. Full article

Background: Perinatal asphyxia is a major cause of neonatal morbidity and mortality, often resulting in hypoxic-ischemic encephalopathy (HIE) with long-term neurodevelopmental impairments. While therapeutic hypothermia has emerged as a promising intervention to reduce brain damage, its specific impact on key brain structures and long-term neurodevelopmental outcomes remains underexplored. This study aims to evaluate the effects of therapeutic hypothermia on brain volumetry, cortical thickness, and neurodevelopment in term neonates with perinatal asphyxia. Methods: This prospective cohort study enrolled 34 term neonates with perinatal asphyxia, with 12 receiving therapeutic hypothermia and 22 serving as controls without hypothermia. Brain MRI data were analyzed using Infant FreeSurfer to quantify the basal ganglia volumes, gray matter, white matter, cerebellum, cortical gyri, and cortical thickness. Neurodevelopmental outcomes were assessed at 18 and 24 months, using the Bayley Scale III, evaluating the motor, cognitive, and language domains. Genetic analyses, including next-generation sequencing (NGS) and microarray testing, were performed to investigate potential neurodevelopmental markers and confounding factors. Results: Neonates treated with hypothermia demonstrated significantly larger gray and white matter volumes, with a 3.7-fold increase in gray matter (p = 0.025) and a 2.2-fold increase in white matter (p = 0.025). Hippocampal volume increased 3.4-fold (p = 0.032) in the hypothermia group. However, no significant volumetric differences were observed in the cerebellum, thalamus, or other subcortical regions. Moderate correlations were found between white matter volume and cognitive outcomes, but these associations were not statistically significant. Conclusions: Therapeutic hypothermia appears to have region-specific neuroprotective effects, particularly in gray and white matter and the hippocampus, which may contribute to improved neurodevelopmental outcomes. However, the impact was not uniform across all brain structures. Further research is needed, to investigate the long-term benefits and to optimize therapeutic strategies by integrating advanced neuroimaging techniques and genetic insights. Full article

Bacterial meningoencephalitis in newborns is a severe and life-threatening pathology, which results from meningeal infection and the subsequent involvement of the brain parenchyma. The severity of the acute onset of symptoms and the risk of neurodevelopmental adverse sequelae in children strongly depend on the timing of the infection, the immunological protection transmitted by the mother to the fetus during pregnancy, and the neonate’s inflammatory and immune system response after birth. Although the incidence of neonatal meningitis and meningoencephalitis and related mortality declined in the past twenty years with the improvement of prenatal care and with the introduction of intrapartum antibiotic prophylaxis against Streptococcus beta Hemolyticus group B (Streptococcus Agalactiae) in the 1990s, bacterial meningitis remains the most common form of cerebrospinal fluid infection in pediatric patients. To date, the rate of unfavorable neurological outcomes is still from 20% to 60%, and the possibility of containing its rate strongly depends on early diagnosis, therapy, and a multidisciplinary approach, which involves neonatologists, neurologists, neuroradiologists, and physiotherapists. Neonatal meningitis remains difficult to diagnose because the responsible bacteria vary with gestational age at birth, age at presentation, and environmental context. The clinical presentation, especially in the newborn, is very ambiguous. From a clinical point of view, the definitive test for diagnosis is lumbar puncture in patients with symptoms suggestive of neurological involvement. Therefore, neuroimaging is key for raising clinical suspicion of meningitis or corroborating the diagnosis based on clinical and laboratory data. Our pictorial review offers a practical approach to neonatal meningoencephalitis by describing the epidemiology, the pathophysiology of bacterial meningoencephalitis, defining the indications and suggesting optimized protocols for neuroimaging techniques, and showing the main neuroimaging findings to reach the diagnosis and offering proper follow-up of bacterial meningitis. Moreover, we tried identifying some peculiar MRI patterns related to some bacteria. Full article

Maternal nutrition during pregnancy is known to be important for offspring growth and health and has also been increasingly recognized for shaping offspring brain development. On the other hand, recent advancements in brain imaging technology have provided unprecedented insights into fetal, neonatal, and pediatric brain morphometry and function. This review synthesizes the current literature regarding the impact of maternal nutrition on offspring brain development, with a specific focus on findings from neuroimaging studies. The diverse effects of maternal nutrients intake or status during pregnancy on neurodevelopmental outcomes in children are discussed. Neuroimaging evidence showed associations between maternal nutrition such as food categories, macronutrients, and micronutrients including vitamins and minerals during pregnancy and child brain imaging features measured using imaging techniques such as ultrasound, magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG). This review demonstrates the capability of neuroimaging in characterizing how maternal nutrition during pregnancy impacts structure and function of the developing brain that may further influence long-term neuropsychological, cognitive, and behavioral outcomes in children. It aims to inspire future research utilizing neuroimaging to deepen our understanding of the critical impacts of maternal nutrition during pregnancy on offspring brain development. Full article

We present the Open Spina Bifida Aperta (OSBA) atlas, an open atlas and set of neuroimaging templates for spina bifida aperta (SBA). Traditional brain atlases may not adequately capture anatomical variations present in pediatric or disease-specific cohorts. The OSBA atlas fills this gap by representing the computationally averaged anatomy of the neonatal brain with SBA after fetal surgical repair. The OSBA atlas was constructed using structural T2-weighted and diffusion tensor MRIs of 28 newborns with SBA who underwent prenatal surgical correction. The corrected gestational age at MRI was 38.1 ± 1.1 weeks (mean ± SD). The OSBA atlas consists of T2-weighted and fractional anisotropy templates, along with nine tissue prior maps and region of interest (ROI) delineations. The OSBA atlas offers a standardized reference space for spatial normalization and anatomical ROI definition. Our image segmentation and cortical ribbon definition are based on a human-in-the-loop approach, which includes manual segmentation. The precise alignment of the ROIs was achieved by a combination of manual image alignment and automated, non-linear image registration. From the clinical and neuroimaging perspective, the OSBA atlas enables more accurate spatial standardization and ROI-based analyses and supports advanced analyses such as diffusion tractography and connectomic studies in newborns affected by this condition. Full article

Accurate prediction of scoliotic curve progression is crucial for guiding treatment decisions in adolescent idiopathic scoliosis (AIS). Traditional methods of assessing the likelihood of AIS progression are limited by variability and rely on static measurements. This study developed and validated machine learning models for classifying progressive and non-progressive scoliotic curves based on gait analysis using wearable inertial sensors. Gait data from 38 AIS patients were collected using seven inertial measurement unit (IMU) sensors, and hip–knee (HK) cyclograms representing inter-joint coordination were generated. Various machine learning algorithms, including support vector machine (SVM), random forest (RF), and novel deep convolutional neural network (DCNN) models utilizing multi-plane HK cyclograms, were developed and evaluated using 10-fold cross-validation. The DCNN model incorporating multi-plane HK cyclograms and clinical factors achieved an accuracy of 92% in predicting curve progression, outperforming SVM (55% accuracy) and RF (52% accuracy) models using handcrafted gait features. Gradient-based class activation mapping revealed that the DCNN model focused on the swing phase of the gait cycle to make predictions. This study demonstrates the potential of deep learning techniques, and DCNNs in particular, in accurately classifying scoliotic curve progression using gait data from wearable IMU sensors. Full article

Anthropometric measures at birth, indexing prenatal growth, are associated with later cognitive development. Children in low- and middle-income countries (LMIC) are at elevated risk for impaired prenatal and early postnatal growth and enduring cognitive deficits. However, the associations of neonatal physical growth with neural activity are not well-characterized in LMIC contexts, given the dearth of early childhood neuroimaging research in these settings. The current study examined birth length, weight, and head circumference as predictors of EEG relative power over the first three years of life in rural Limpopo Province, South Africa, controlling for postnatal growth and socioeconomic status (SES). A larger head circumference at birth predicted lower relative gamma power, lower right hemisphere relative beta power, and higher relative alpha and theta power. A greater birth length also predicted lower relative gamma power. There were interactions with timepoints such that the associations of birth head circumference and length with EEG power were most pronounced at the 7-month assessment and were attenuated at the 17- and 36-month assessments. The results identify birth head circumference and length as specific predictors of infant neural activity within an under-resourced context. Full article

(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes ERCC6 (CS type B) and ERCC8 (CS type A). We assessed this, presenting a series of patients with genetically confirmed CSB. (2) Materials and Methods: We retrospectively collected demographic, clinical, genetic, neuroimaging, and serum neurofilament light-chain (sNFL) data about CSB patients; diagnostic and severity scores were also determined. (3) Results: Data of eight ERCC6/CSB patients are presented. Four patients had CS I, three patients CS II, and one patient CS III. Various degrees of ataxia and spasticity were cardinal neurologic features, with variably combined systemic characteristics. Mean age at diagnosis was lower in the type II form, in which classic CS signs were more evident. Interestingly, sNFL determination appeared to reflect clinical classification. Two novel premature stop codon and one novel missense variants were identified. All CS I subjects harbored the p.Arg735Ter variant; the milder CS III subject carried the p.Leu764Ser missense change. (4) Conclusion: Our work confirms clinical variability also in the ERCC6/CSB type, where manifestations may range from severe involvement with prenatal or neonatal onset to normal psychomotor development followed by progressive ataxia. We propose, for the first time in CS, sNFL as a useful peripheral biomarker, with increased levels compared to currently available reference values and with the potential ability to reflect disease severity. Full article

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been examined to the age of school entry level. A total of 51 Colombian children with antenatal ZIKV exposure without CZS and 70 unexposed controls were evaluated at 4–5 years of age using the Behavior Rating Inventory of Executive Function (BRIEF), the Pediatric Evaluation of Disability Inventory (PEDI-CAT), the Bracken School Readiness Assessment (BSRA), and the Movement Assessment Battery for Children (MABC). The mean ages at evaluation were 5.3 and 5.2 years for cases and controls, respectively. Elevated BRIEF scores in Shift and Emotional Control may suggest lower emotional regulation in cases. A greater number of cases were reported by parents to have behavior and mood problems. BSRA and PEDI-CAT activity scores were unexpectedly higher in cases, most likely related to the COVID-19 pandemic and a delayed school entry among the controls. Although PEDI-CAT mobility scores were lower in cases, there were no differences in motor scores on the MABC. Of 40 cases with neonatal neuroimaging, neurodevelopment in 17 with mild non-specific findings was no different from 23 cases with normal neuroimaging. Normocephalic children with ZIKV exposure have positive developmental trajectories at 4–5 years of age but differ from controls in measures of emotional regulation and adaptive mobility, necessitating continued follow-up. Full article

In drug-resistant epilepsy, a visual inspection of intracranial electroencephalography (iEEG) signals is often needed to localize the epileptogenic zone (EZ) and guide neurosurgery. The visual assessment of iEEG time-frequency (TF) images is an alternative to signal inspection, but subtle variations may escape the human eye. Here, we propose a deep learning-based metric of visual complexity to interpret TF images extracted from iEEG data and aim to assess its ability to identify the EZ in the brain. We analyzed interictal iEEG data from 1928 contacts recorded from 20 children with drug-resistant epilepsy who became seizure-free after neurosurgery. We localized each iEEG contact in the MRI, created TF images (1–70 Hz) for each contact, and used a pre-trained VGG16 network to measure their visual complexity by extracting unsupervised activation energy (UAE) from 13 convolutional layers. We identified points of interest in the brain using the UAE values via patient- and layer-specific thresholds (based on extreme value distribution) and using a support vector machine classifier. Results show that contacts inside the seizure onset zone exhibit lower UAE than outside, with larger differences in deep layers (L10, L12, and L13: p < 0.001). Furthermore, the points of interest identified using the support vector machine, localized the EZ with 7 mm accuracy. In conclusion, we presented a pre-surgical computerized tool that facilitates the EZ localization in the patient’s MRI without requiring long-term iEEG inspection. Full article

Background: Magnetic resonance imaging (MRI) including diffusion-weighted imaging within seven days after birth is widely used to obtain prognostic information in neonatal encephalopathy (NE) following perinatal asphyxia. Later MRI could be useful for infants without a neonatal MRI or in the case of clinical concerns during follow-up. Therefore, this review evaluates the association between cranial MRI beyond the neonatal period and neurodevelopmental outcomes following NE. Methods: A systematic literature search was performed using PubMed and Embase on cranial MRI between 2 and 24 months after birth and neurodevelopmental outcomes following NE due to perinatal asphyxia. Two independent researchers performed the study selection and risk of bias analysis. Results were separately described for MRI before and after 18 months. Results: Twelve studies were included (high-quality n = 2, moderate-quality n = 6, low-quality n = 4). All reported on MRI at 2–18 months: seven studies demonstrated a significant association between the pattern and/or severity of injury and overall neurodevelopmental outcomes and three showed a significant association with motor outcome. There were insufficient data on non-motor outcomes and the association between MRI at 18–24 months and neurodevelopmental outcomes. Conclusions: Cranial MRI performed between 2 and 18 months after birth is associated with neurodevelopmental outcomes in NE following perinatal asphyxia. However, more data on the association with non-motor outcomes are needed. Full article

Background: Cutting-edge neonatal programs diagnose cerebral palsy (CP) or “high risk of CP” using validated neurobehavioral exams in combination with risk history and neuroimaging. In rat models, digital gait analyses are the gold standard adult assessment, but tools in infant rats are limited. Refinement of infant rat neurobehavioral correlates of CP will establish translational behavioral biomarkers to delineate early mechanisms of CP in both humans and rodent models of CP. Objective: To facilitate precision medicine approaches of neurodevelopmental health and integrate basic and clinical research approaches for CP, we developed and piloted a new assay of neonatal rat neurobehavior to mimic human neonate exams. Methods: Our established rat model of CP secondary to chorioamnionitis (CHORIO) that induces bilateral motor impairment reminiscent of spastic CP was used. On postnatal day 10 (P10), 5 min videos were recorded of 26 (6 sham and 20 CHORIO) animals moving freely in a cage were reviewed by an evaluator trained in the human General Movements Assessment (GMA). Non-blinded observation revealed two behaviors that differed between rat pups in each group (time spent rearing; multi-dimensional nose sweeping; and sniffing). Each video was re-coded for these criteria by an evaluator blind to group status. Differences between sham and CP groups were analyzed using a Mann–Whitney U-test or Student’s t-test (p < 0.05 level of significance). Results: Neonatal rats with CP exhibited sensorimotor impairment and decreased spatial exploration. CP rats spent significantly less time rearing (17.85 ± 1.60 s vs. 34.8 ± 2.89 s, p = 0.007) and engaged in multi-dimensional nose sweeping and sniffing (2.2 ± 0.58 episodes vs. 5.5 ± 0.96 episodes, p = 0.03) than sham controls. Conclusions: These pilot findings of harmonized translational and precision biobehavioral assays provide an opportunity for increased expediency of clinical trials at the earliest stages of brain development. Full article