Intracranial empyema complicating sinusitis in childhood: Epidemiology, imaging findings and outcome.

BACKGROUND: To describe clinical presentations of intracranial sinusitis complications in childhood, their pitfalls and imaging findings. MATERIEL AND METHODS: This retrospective IRB-approved single-center study included infants diagnosed with sinusitis and empyema and/or other intracranial complications who underwent imaging between September 2008 and September 2019. Three radiologists individually reviewed clinical charts and imaging findings, including sinusitis complications and at-risk anatomical variations. RESULTS: 21 children (76% males and 24% females, mean age 13±3.1 years) with imaging pansinusitis were included. Headache (95%) and fever (90%) were the main clinical nonspecific signs. Ten (48%) children presented an extradural empyema, nine (43%) children had a subdural empyema and two (10%) children had both. Frontal location sinusitis was the most common (76%). In MRI, all empyema presented as a hypo intensity on pre-contrast T1-WI, a hyperintensity on T2-WI, a reduced apparent diffusion coefficient (ADC) on diffusion weighted imaging (DWI) and a peripheral contrast enhancement on post-contrast T1-WI. CT or MRI revealed intracranial complications such as a collection size increase (52%), a midline shift (62%), intraparenchymal abscesses (24%), a cerebral venous thrombosis (29%), an intracranial pressure increase (29%), cerebral ischemia (43%) and Pott's Puffy Tumor (10%). Imaging highlighted sinus anatomical abnormalities in 52% of cases. All children were treated with sinus drainage and/or neurosurgery. Long-term follow-up was favorable in 14 cases (67%). CONCLUSION: Complications of sinusitis are life threatening in the studied population. Empyema and cerebral complications may be misleading. Brain contrast-enhanced CT covering sinuses and orbits, is mainly the first examination done but MRI is mandatory.

Hemidystonia with polymicrogyria is part of ATP1A3-related disorders.

INTRODUCTION: Pathogenic variants in ATP1A3 cause various phenotypes of neurological disorders, including alternating hemiplegia of childhood 2, CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) and rapid-onset dystonia-parkinsonism (RDP). Early developmental and epileptic encephalopathy has also been reported. Polymicrogyria has recently been added to the phenotypic spectrum of ATP1A3-related disorders. CASE REPORT: We report here a male patient with early developmental delay who at 12 months presented dystonia of the right arm which evolved into hemidystonia at the age of 2. A cerebral MRI showed bilateral perisylvian polymicrogyria with intact basal ganglia. Whole-exome and whole-genome sequencing analyses identified a de novo new ATP1A3 missense variant (p.Arg914Lys) predicted pathogenic. Hemidystonia was thought not to be due to polymicrogyria, but rather a consequence of this variant. CONCLUSION: This case expands the phenotypic spectrum of ATP1A3-related disorders with a new variant associated with hemidystonia and polymicrogyria and thereby, suggests a clinical continuum between the different phenotypes of this condition.

Childhood cancer risks estimates following CT scans: an update of the French CT cohort study.

OBJECTIVES: Increased risks of central nervous system (CNS) tumors and leukemia associated with computed tomography (CT) exposure during childhood have been reported in recent epidemiological studies. However, no evidence of increased risks was suggested in a previous analysis of the French CT cohort. This study benefits from an updated cohort with a longer follow-up and a larger sample size of patients. METHODS: The patients were followed from the date of their first CT (between 2000 and 2011) until their date of cohort exit defined as the earliest among the following: 31 December 2016, date of death, date of first cancer diagnosis or date of their 18th birthday. Cancer incidence, vital status, cancer predisposing factors (PFs), and additional CT scans were collected via external national databases. Hazard ratios (HRs) associated to cumulative organ doses and sex were estimated from Cox models. RESULTS: At the end of follow-up, mean cumulative doses were 27.7 and 10.3 mGy for the brain and the red bone marrow (RBM), respectively. In patients without PFs, an HR per 10 mGy of 1.05 (95% CI: 1.01-1.09) for CNS tumors, 1.17 (95% CI: 1.09-1.26) for leukemia, and 0.96 (95% CI: 0.63-1.45) for lymphoma was estimated. These estimates were not modified by the inclusion of CT scans performed outside the participating hospitals or after the inclusion period. CONCLUSIONS: This study shows statistically significant dose-response relationships for CNS tumors and leukemia for patients without PFs. KEY POINTS: • Computed tomography is the most important contributor to the collective dose for diagnostic imaging to the French population. • Concerns have been raised about possible cancer risks, particularly after exposure to CT in childhood, due to the greater radiation sensitivity of children and to their longer life expectancy. • Analysis of the updated French CT cohort shows statistically significant dose-response relationships for CNS tumors and leukemia.

A practical guide to optimize arterial spin labeling in neonates at 1.5 Tesla: what the radiologist needs to know.

Arterial spin labeling magnetic resonance imaging is highly suited to the exploration of brain perfusion in neonates and has the potential to provide relevant complementary information to neuroimaging studies, with insights into neurodevelopmental outcomes. Applying this technique within the first days of life is challenging and requires specific technical adaptations. The literature on this topic is scarce and heterogeneous, especially on 1.5-T scanners, limiting widespread clinical adoption. This paper aims to describe a simple approach for arterial spin labeling in neonates, with key considerations for radiologists.

Cystic fibrosis and noninvasive liver fibrosis assessment methods in children.

BACKGROUND: Noninvasive assessments of liver fibrosis are currently used to evaluate cystic fibrosis (CF)-related liver disease. However, there is scarce data regarding their repeatability and reproducibility, especially in children with CF. The present study aimed to evaluate the repeatability and reproducibility of transient elastography (TE) (FibroScan®) and point shear-wave elastography using virtual touch quantification (pSWE VTQ) in children with CF. METHODS: TE and pSWE VTQ were performed in 56 children with CF by two different operators. Analysis of repeatability and reproducibility was available in 33 patients for TE and 46 patients for pSWE VTQ. Intra- and interobserver agreement were assessed using the intraclass correlation coefficient (ICC) and their 95% confidence interval (CI), and Bland and Altman graphs. RESULTS: For TE, ICC was 0.91 (0.83-0.95) for intraobserver agreement and 0.92 (95% CI: 0.86-0.96) for interobserver agreement. For pSWE VTQ, ICC was 0.83 (0.72-0.90) for intraobserver agreement and 0.67 (0.48-0.80) for interobserver agreement. CONCLUSIONS: Both technics can be proposed in the follow-up of patients, according to their availability in CF centers. IMPACT: This study shows that TE and pSWE VTQ are reliable methods to evaluate liver fibrosis in children with CF. This study shows for the first time that TE and pSWE VTQ are both repeatable and reproducible in children with CF. These data indicate that both TE and pSWE VTQ can be proposed for the follow-up of patients with CF, according to their availability in each CF center.

Brain fetal magnetic resonance imaging to evaluate maturation of normal white matter during the third trimester of pregnancy.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) could improve the estimation of fetal brain maturation and the interpretation of white matter signal intensity in pathological conditions. OBJECTIVE: To investigate T2-based and diffusion-weighted imaging (DWI) measurements for the evaluation of fetal brain maturation during the last trimester of pregnancy. MATERIALS AND METHODS: One hundred sixty-eight fetal brain MRIs were retrospectively analyzed (age range: 28-37 weeks of gestation) after ensuring that none of the children developed psychomotor or cognitive impairment (median follow-up: 4.7 years). Bilateral regions of interest were drawn on the frontal, occipital, parietal and temporal lobes from T2-W imaging and DWI, when available, to evaluate signal intensity and apparent diffusion coefficient (ADC) values. Ratios were calculated with two references (pons or thalamus and cerebrospinal fluid) to standardize signal intensities. Reproducibility was evaluated with intraclass correlation coefficients (ICCs) and Bland-Altman plots. Correlations with gestational age were evaluated with univariate and multivariate linear regressions. RESULTS: T2 measurements were achieved in all cases, and DWI was available in 37 cases. Measurements and ratios were reproducible in eight localizations (i.e. intra- and interobserver ICCs >0.5): frontal T2/thalamus, parietal T2/thalamus, occipital T2/pons, parietal ADC/thalamus, occipital ADC/pons, temporal ADC/pons, occipital ADC and temporal ADC. The frontal T2/thalamus and parietal T2/thalamus correlated with gestational age (P<0.0001 and P=0.014, respectively). In the multivariate modeling, frontal T2/thalamus remained an independent predictor of the gestational age (P<0.0001). CONCLUSION: The frontal T2/thalamus ratio emerged as a potential additional biomarker of fetal brain maturation during the last trimester of pregnancy.

Brain MRI after therapeutic hypothermia in asphyxiated newborns: Predictive value at one year of imaging features.

PURPOSE: To compare early brain MRI using a composite imaging score and outcome at one year in asphyxiated newborns treated by hypothermia. METHODS: This retrospective study included for two years consecutive asphyxiated term newborns treated by hypothermia for hypoxic-ischemic encephalopathy, and who had brain MRI before day 8. Therapeutic hypothermia was initiated within the first 6 h of life and continued for 72 h. Imaging protocol included T1 and T2 sequences, diffusion-weighted imaging (DWI), evaluated with a specific composite score, and spectroscopy. Clinical evaluation was performed at one year of age, outcome was classified as favorable/unfavorable. The primary endpoint was the correlation between our MRI score and outcome with the definition of a threshold. The secondary endpoints were to find the most relevant criteria within the score and to evaluate objective signal measurements to support subjective criteria. RESULTS: Among the 33 included patients, 9 died during the first days of life, 20 had a favorable outcome, 4 an unfavorable one. MRI score was correlated to a poor clinical outcome (p < 0.001). Most of the criteria within the score and spectroscopy results were relevant (p < 0.05). Cerebral edema was objectively assessed by the signal intensity ratio of white matter compared to cerebrospinal fluid (CSF) on T2-weighted images (p < 0.001). CONCLUSION: MRI score was predictive of neurodevelopmental outcome at one year. The most relevant criteria within the score were DWI abnormalities in basal ganglia and thalami and loss of white-cortical grey matter differentiation. Signal intensity ratio between white matter and CSF higher than 0.75 supports the presence of edema.

[Nephrocalcinosis in children]. / Néphrocalcinose de l'enfant.

Nephrocalcinosis is defined by calcium phosphate or calcium oxalate deposits in the kidney parenchyma, particularly in tubular epithelial cells and interstitial tissue. It should be differentiated from urolithiasis where calcium salts deposits are located in the kidney and urinary tract. The epidemiology of nephrocalcinosis in children is unknown but the condition is not so rare, with an increased incidence in preterm infants. Often detected as an incidental finding, nephrocalcinosis may be classified according to the radiological type: medullary, cortical or diffuse. Nephrocalcinosis in children can be caused by a variety of etiology. The most common causes concern medullary nephrocalcinosis and include hereditary tubular disorders, in particular distal renal tubular acidosis and Dent disease, metabolic disorders such as idiopathic hypercalciuria and hyperoxaluria, and iatrogenic causes such as vitamin D intoxication. In the newborn, the main cause is hypercalciuria of the premature baby, whose multifactorial origin is largely iatrogenic. Primary hyperoxaluria which can lead to early onset nephrocalcinosis and usually to chronic kidney disease should always be considered and further investigated. In order to provide a specific diagnosis, it is essential to take into account the family history, the clinical context and complete laboratory data. Early initiation of an appropriate etiological treatment is recommended and may prevent or delay the progression to chronic kidney disease in some cases.

Neuroprotective role of lactate in rat neonatal hypoxia-ischemia.

Hypoxic-ischemic (HI) encephalopathy remains a major cause of perinatal mortality and chronic disability in newborns worldwide (1-6 for 1000 births). The only current clinical treatment is hypothermia, which is efficient for less than 60% of babies. Mainly considered as a waste product in the past, lactate, in addition to glucose, is increasingly admitted as a supplementary fuel for neurons and, more recently, as a signaling molecule in the brain. Our aim was to investigate the neuroprotective effect of lactate in a neonatal (seven day old) rat model of hypoxia-ischemia. Pups received intra-peritoneal injection(s) of lactate (40 µmol). Size and apparent diffusion coefficients of brain lesions were assessed by magnetic resonance diffusion-weighted imaging. Oxiblot analyses and long-term behavioral studies were also conducted. A single lactate injection induced a 30% reduction in brain lesion volume, indicating a rapid and efficient neuroprotective effect. When oxamate, a lactate dehydrogenase inhibitor, was co-injected with lactate, the neuroprotection was completely abolished, highlighting the role of lactate metabolism in this protection. After three lactate injections (one per day), pups presented the smallest brain lesion volume and a complete recovery of neurological reflexes, sensorimotor capacities and long-term memory, demonstrating that lactate administration is a promising therapy for neonatal HI insult.

Improved stenosis outcome in stroke-free sickle cell anemia children after transplantation compared to chronic transfusion.

We report here the 3-year stenosis outcome in 60 stroke-free children with sickle cell anaemia (SCA) and an abnormal transcranial Doppler history, enrolled in the DREPAGREFFE trial, which compared stem cell transplantation (SCT) with standard-care (chronic transfusion for 1-year minimum). Twenty-eight patients with matched sibling donors were transplanted, while 32 remained on standard-care. Stenosis scores were calculated after performing cerebral/cervical 3D time-of-flight magnetic resonance angiography. Fourteen patients had stenosis at enrollment, but only five SCT versus 10 standard-care patients still had stenosis at 3 years. Stenosis scores remained stable on standard-care, but significantly improved after SCT (P = 0·006). No patient developed stenosis after SCT, while two on standard-care did, indicating better stenosis prevention and improved outcome after SCT.

Childhood Langerhans cell histiocytosis with severe lung involvement: a nationwide cohort study.

BACKGROUND: Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed. METHODS: Among 1482 children (< 15 years) registered in the French LCH registry (1994-2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure. RESULTS: The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine-corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging. CONCLUSIONS: Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.

Chest computed tomography findings for a cohort of children with pulmonary Langerhans cell histiocytosis.

OBJECTIVE: This study was undertaken to describe the spectrum of lung computed-tomography (CT) findings in children with pulmonary Langerhans cell histiocytosis (PLCH) and to evaluate for this population the CT-scan nodule and cyst scores proposed by adult pulmonologists at diagnosis and during follow-up. METHODS: Among 175 children with PLCH identified in the French national population-based Langerhans cell histiocytosis cohort, 60 were retrospectively selected by the availability of CT for a central review by three pediatric radiologists. These 60 patients are representative of childhood PLCH for almost all clinical aspects, except a lower percentage of risk organ involvement (38% vs 54%; P = 0.05). RESULTS: The 60 children's chest CT scans (n = 218) were reviewed. At diagnosis, 63% of them had nodules, 53% had cysts, and 29% had both. The percentages of patients with nodules or cysts increased from diagnosis to peak disease activity, respectively, from 63% to 73% and from 53% to 66%. The costophrenic angle was involved in 71%. Patients with pneumothorax (25%) had a higher median cyst score. Alveolar consolidation was observed in 34%. Patients with low CT-scan nodule and cyst scores had no long-term pulmonary sequelae. CONCLUSIONS: Well-known characteristics of adult PLCH (nodules and cysts) were observed in children. The chest CT scores proposed by adult pulmonologists could easily be applied to childhood PLCH. Lesions in children, unlike those in adults, are frequently located near the costophrenic angles. Alveolar consolidation might be considered an atypical feature of childhood PLCH.

Magnetic resonance imaging diagnosis of subependymal giant cell astrocytomas in follow-up of children with tuberous sclerosis complex: should we always use contrast enhancement?

BACKGROUND: Subependymal giant cell astrocytomas (SEGAs) arise in 10-26% of tuberous sclerosis complex (TSC) patients. SEGAs cause obstructive hydrocephalus and increase morbi-mortality. It is recommended that TSC patients be followed with contrast enhanced magnetic resonance imaging (CE-MRI), but repetitive use of gadolinium-based contrast-agents (GBCAs) may cause organ deposits. OBJECTIVE: To compare the diagnostic performances of non-CE- and CE-MRI to differentiate SEGAs from subependymal nodules in TSC patients during follow-up. MATERIALS AND METHODS: Thirty-five TSC patients (median age: 2.4 years) were enrolled in this retrospective single-center study from September 2007 to January 2019. Inclusion criteria were a certain diagnosis of TSC and at least three follow-up brain MRIs with GBCA injection. Two consecutive MRI scans per patient were selected and anonymized. Three radiologists performed a blinded review of non-enhanced and enhanced MRI sequences during different sessions. The diagnostic performances were compared (sensitivity, specificity, positive/negative predictive values, accuracy, inter/intra-observer agreements). RESULTS: The accuracies for detecting SEGAs were good and similar between the non-enhanced and enhanced MRI sequences. The sensitivity and specificity of non-CE-MRI to diagnose SEGA ranged from 75% to 100% and from 94% to 100%, respectively. The differences in numbers of false-positive and false-negative patients between non-CE- and CE-MRI never exceeded one case. Nodules size >10 mm, location near the Monro foramen, hydrocephalus and modifications between two consecutive MRI scans were significantly associated with the diagnosis of SEGA for the three readers (all P-values <0.05). Inter- and intra-observer agreements were also excellent for non-enhanced and enhanced MRI sequences (kappa=0.85-1 and 0.81-0.93, respectively). CONCLUSION: The performances of non-enhanced and enhanced MRI sequences are comparable for detecting SEGAs, questioning the need for systematic GBCA injections for TSC patients.

Impact at school age of early chronic methicillin-sensitive Staphylococcus aureus infection in children with cystic fibrosis.

BACKGROUND: Bacterial infection early in life may increase structural lung lesions in children with cystic fibrosis (CF). METHODS: A 9-year monocentric (Bordeaux University Hospital, France) retrospective study in children with CF to evaluate the impact of the early-onset (at 1 year of age, Y1) of chronic meticillin-sensitive Staphylococcus aureus (MSSA) infection on the severity of bronchiectasis and Bhalla score on CT scan, clinical status, lung function tests, and serum immunoglobulins (IgG) at the age of 6 years (Y6). RESULTS: A total of 37 children were included: 10 had contracted chronic MSSA infection at Y1 and 27 at a later date. Children with MSSA infection at Y1 showed increased Y6 CT scan bronchiectasis severity scores vs late MSSA infection (mean ± SD: 4.7 ± 0.8 vs 2.5 ± 0.5, P < .05) and Bhalla scores (7.3 ± 1.1 vs 4.7 ± 0.8, P < .05), but no significant decrease in lung function ([% reference values] FEV1: 83.7 ± 6 vs 90.6 ± 2.2, P = .21; FEF25-75: 67.8 ± 8.9 vs 76.3 ± 3.9, P = .18). In addition, Y6 serum IgG was greater in the early chronic Y1 MSSA group (11.3 ± 0.7 vs 8.9 ± 0.7 g/L, P < .05). Clinical symptoms or nutritional status were similar in both infection groups. CONCLUSION: Early chronic MSSA infection may enhance the progression of structural lung disease in CF at 6 years.

Maternal alcoholism and neonatal hypoxia-ischemia: Neuroprotection by stilbenoid polyphenols.

The impact of maternal nutrition on neurodevelopment and neonatal neuroprotection is a research topic with increasing interest. Maternal diet can also have deleterious effects on fetal brain development. Fetal exposure to alcohol is responsible for poor neonatal global development, and may increase brain vulnerability to hypoxic-ischemic encephalopathy, one of the major causes of acute mortality and chronic neurological disability in newborns. Despite frequent prevention campaigns, about 10% of women in the general population drinks alcohol during pregnancy and breastfeeding. This study was inspired by this alarming fact. Its aim was to evaluate the beneficial effects of maternal supplementation with two polyphenols during pregnancy and breastfeeding, on hypoxic-ischemic neonate rat brain damages, sensorimotor and cognitive impairments, in a context of moderate maternal alcoholism. Both stilbenoid polyphenols, trans-resveratrol (RSV - 0.15 mg/kg/day), and its hydroxylated analog, trans-piceatannol (PIC - 0.15 mg/kg/day), were administered in the drinking water, containing or not alcohol (0.5 g/kg/day). In a 7-day post-natal rat model of hypoxia-ischemia (HI), our data showed that moderate maternal alcoholism does not increase brain lesion volumes measured by MRI but leads to higher motor impairments. RSV supplementation could not reverse the deleterious effects of HI coupled with maternal alcoholism. However, PIC supplementation led to a recovery of all sensorimotor and cognitive functions. This neuroprotection was obtained with a dose of PIC corresponding to the consumption of a single passion fruit per day for a pregnant woman.

Pediatric minor head injury imaging practices: results from an ESPR survey.

PURPOSE: Computed tomography (CT) for minor head injury exposes a large number of children to ionizing radiation, with an associated increased lifetime risk of malignancy. To study imaging practices for children with minor head injury and the level of awareness of radiologists of the current clinical decision rules for minor traumatic brain injury (TBI). METHODS: A questionnaire consisting of 17 questions was distributed electronically to 472 ESPR members. The questionnaire covered demographic information, employment status, years of experience and the current practice setting of the participants, the number of CTs performed for pediatric head trauma, awareness of clinical decision rules and use of shielding, pediatric CT protocol and MRI. RESULTS: The response rate was 18.4%. The majority of participants was aged over 50 years and was full-time consultants. Regarding decision rules, 73.8% of respondents cited the NICE head injury guidelines, and 79% reported that the decision to perform CT was agreed between specialists. Shielding was used by 58.3% and 67.4% applied a specific pediatric protocol. MRI was not used for pediatric head trauma by 70.6% of respondents, although always available in 68.6% of cases. The reported obstacles to MRI use were machine availability (42.7%), the long acquisition time (39%) and patients' intolerance (18.3%), and less frequently the cost and the need for sedation. CONCLUSION: There is room for decreasing the use of CT for pediatric minor TBI. The use of shielding and application of pediatric CT protocols constitute areas for improvement.

Neuroprotective Effect of Maternal Resveratrol Supplementation in a Rat Model of Neonatal Hypoxia-Ischemia.

Neonatal hypoxia-ischemia (nHI) is a major cause of death or subsequent disabilities in infants. Hypoxia-ischemia causes brain lesions, which are induced by a strong reduction in oxygen and nutrient supply. Hypothermia is the only validated beneficial intervention, but not all newborns respond to it and today no pharmacological treatment exists. Among possible therapeutic agents to test, trans-resveratrol is an interesting candidate as it has been reported to exhibit neuroprotective effects in some neurodegenerative diseases. This experimental study aimed to investigate a possible neuroprotection by resveratrol in rat nHI, when administered to the pregnant rat female, at a nutritional dose. Several groups of pregnant female rats were studied in which resveratrol was added to drinking water either during the last week of pregnancy, the first week of lactation, or both. Then, 7-day old pups underwent a hypoxic-ischemic event. Pups were followed longitudinally, using both MRI and behavioral testing. Finally, a last group was studied in which breastfeeding females were supplemented 1 week with resveratrol just after the hypoxic-ischemic event of the pups (to test the curative rather than the preventive effect). To decipher the molecular mechanisms of this neuroprotection, RT-qPCR and Western blots were also performed on pup brain samples. Data clearly indicated that when pregnant and/or breastfeeding females were supplemented with resveratrol, hypoxic-ischemic offspring brain lesions were significantly reduced. Moreover, maternal resveratrol supplementation allowed to reverse sensorimotor and cognitive deficits caused by the insult. The best recoveries were observed when resveratrol was administered during both gestation and lactation (2 weeks before the hypoxic-ischemic event in pups). Furthermore, neuroprotection was also observed in the curative group, but only at the latest stages examined. Our hypothesis is that resveratrol, in addition to the well-known neuroprotective benefits via the sirtuin's pathway (antioxidant properties, inhibition of apoptosis), has an impact on brain metabolism, and more specifically on the astrocyte-neuron lactate shuttle (ANLS) as suggested by RT-qPCR and Western blot data, that contributes to the neuroprotective effects.