Mild Encephalopathy Research Articles

Mild Encephalopathy with Reversible Splenic Lesions in an Infant with COVID-19

There have been few reports of mild encephalopathy with reversible splenic lesions (MERS) associated with COVID-19 in infants. Here, we present a case of MERS in a 23-month-old infant with COVID-19 in Japan during the Omicron variant epidemic. The increase in COVID-19 acute encephalopathy in infants, including those with MERS, should be considered in the future due to the prevalence of the Omicron variant strain. Meanwhile, whether the cause is COVID-19, acute encephalopathy with a lesion localized in the splenium of the corpus callosum can be treated with temporary anticonvulsant therapy, as is generally the case with MERS.

Splenium of the Corpus Callosum Infarct Associated With COVID-19: Case Report.

Coronavirus disease 2019 (COVID-19) has been recently associated with infarction of the central splenium of the corpus callosum. These are described as cytotoxic lesions, and imaging rarely reveals enhancement. They have not been described in the body or head of the corpus callosum. Few diseases affect the corpus callosum, but the most common include multiple sclerosis, aquaporin-4 disease, and Susac syndrome. There is also emerging literature on Mild Encephalopathy with Reversible Splenial lesions associated with central and not basal lesions. The reason for the location of these lesions in acute COVID-19 infection is unknown. A 22-year-old female presented to the ED for altered mental status after being found down. A brief history review indicated that the patient had been altered for 2-3 days before being found naked and covered in her own feces and urine by her family after they had not heard from her. As she lived alone, a clear history of the events preceding her admission remains unclear. On initial assessment, the patient was found to be somnolent and nonverbal, though she could follow simple commands. On admission, testing for SARS CoV-2 RNA PCR was positive. Patient was admitted to the hospital for further work up to determine the cause of the altered mental status. We present a new case of a young woman who developed a central splenium lesion during acute COVID-19 infection and explain the predilection for the callosum in these patients, as well as literature to show that COVID-19 was most likely the cause.

Hyperosmolar Hyperglycemic State as a Stroke Mimic

Hyperosmolar hyperglycemic state (HHS) is a medical emergency, characterized by hyperosmolarity, hyperglycemia, and intravascular volume depletion, in the absence of ketosis. The spectrum of neurological manifestations in HHS is diverse, ranging from mild encephalopathy to coma. The common neurological presentations of HHS include encephalopathy, seizures, and hyperkinetic movement disorders. Stroke-like presentation of HHS is less reported. We report the case of an elderly female, with uncontrolled type 2 diabetes mellitus, who presented with left hemiplegia and, on evaluation, she was diagnosed to have HHS. As she was a chronic kidney disease patient, this case posed challenges in fluid management, which forms the corner stone of HHS management, along with insulin administration. She was discharged at the end of 1 week, with a complete resolution of her neurological deficit.

Commentary to Adverse short- and long-term outcomes among infants with mild neonatal encephalopathy PR-2022-0126.

Commentary to Adverse short- and long-term outcomes among infants with mild neonatal encephalopathy PR-2022-0126.

Outcomes in children after mild neonatal hypoxic ischaemic encephalopathy: A population-based cohort study.

To investigate whether mild neonatal hypoxic ischaemic encephalopathy (HIE) in term born infants is associated with cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. Population-based cohort study. Sweden, 2009-2015. Live term born infants without congenital malformations or chromosomal abnormalities (n = 505 075). Birth and health data were retrieved from Swedish national health and quality registers. Mild HIE was identified by diagnosis in either the Swedish Medical Birth Register or the Swedish Neonatal Quality Register. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). A composite of the outcomes cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. Median follow-up time was 3.3 years after birth. Of 414 infants diagnosed with mild HIE, 17 were classified according to the composite outcome and incidence rates were 12.6 and 2.9 per 1000 child-years in infants with and without HIE respectively. Infants with mild HIE was four times as likely to be diagnosed with the composite outcome (HR 4.42, 95% CI 2.75-7.12) compared with infants without HIE. When analysed separately, associations were found with cerebral palsy (HR 21.50, 95% CI 9.59-48.19) and death (HR 19.10, 95% CI 7.90-46.21). HRs remained essentially unchanged after adjustment for covariates. Mild neonatal HIE was associated with neurological morbidity and mortality in childhood. Challenges include identifying infants who may develop morbidity and how to prevent adverse outcomes.

Distribution of the misfolded isoform of the prion protein in peripheral tissues and spinal cord of Rocky Mountain elk (Cervus elaphus nelsoni) with naturally occurring chronic wasting disease.

Chronic wasting disease (CWD) is an infectious transmissible spongiform encephalopathy of cervids associated with the presence of a misfolded prion protein (PrPCWD). Progression of PrPCWD distribution has been described using immunohistochemistry and histologic changes in a single section of brain stem at the level of the obex resulting in scores from 0 (early) to 10 (terminal) in elk with naturally occurring CWD. Here we describe the spread and distribution of PrPCWD in peripheral tissues and spinal cord in 16 wild and 17 farmed Rocky Mountain elk (Cervus elaphus nelsoni) with naturally occurring CWD and correlate these findings with obex scores. Spinal cord and approximately 110 peripheral tissues were collected, processed, stained with hematoxylin and eosin, and immunolabeled with the anti-prion protein monoclonal antibody F99/97.6.1. The medial retropharyngeal and tracheobronchial lymph nodes were the first tissues to accumulate PrPCWD, followed by other lymphoid tissues, myenteric plexus, spinal cord, and finally tissues outside of the lymphatic and neural systems. However, the only significant histological lesion observed was mild spongiform encephalopathy in the dorsal column of the lower spinal cord in elk with an obex score of ≥9. Initial exposure to CWD prions may be through the respiratory system and spread appears to occur primarily via the autonomic nervous system. Therefore, we suggest using obex scores as a proxy for stage of disease progression and verifying with key peripheral tissues.

Neurosyphilis Presenting as Limbic Encephalitis: a Case Report (P10-10.007)

<h3>Objective:</h3> To present an interesting case of neurosyphilis mimicking limbic encephalitis. <h3>Background:</h3> Neurosyphilis can occur at any stage of infection and it classically presents as meningitis, cranial neuropathies, vasculitis, tabes dorsalis, or neuropsychiatric manifestations, however rarely temporal lobe abnormalities resembling limbic encephalitis have been reported. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> 51-year-old male with no past medical history presents initially with 3 weeks of altered mental status, confusion and memory loss. Prior to admission to the hospital, he presented with a generalized tonic-clonic seizure. His MRI showed T2 hyperintensities in the left hippocampus, amygdala, and mesial temporal lobe with associated diffusion restriction. Cerebrospinal fluid (CSF) studies showed 58 white blood cells/mm3 (73% lymphocytes), a protein concentration of 165 mg/dL and a glucose concentration of 35 mg/dL. HIV serology, serum cryptococcal Antigen, HSV and VZV PCR on CSF and neuronal autoantibodies on serum were negative. EEG showed left lateralized periodic discharges. The patient was initially treated with empiric anti-infective therapy including acyclovir, ceftriaxone, and ampicillin. Subsequently, serum syphilis screen was positive with reflex Rapid Plasma Reagin (RPR) titer at 1:64. CSF Venereal Disease Research Laboratory (VDRL) was positive at 1:64. In light of these results, the patient was transitioned to intravenous aqueous penicillin G 24 million units daily through continuous infusion. His mental status markedly improved after a few days of treatment. Repeat EEG showed only mild encephalopathy. He was discharged on levetiracetam and high dose IV penicillin G to complete a 14-day course. <h3>Conclusions:</h3> Syphilis is commonly known as a great imitator; it is a treatable condition so it should not be missed. We need to be more cognizant of this diagnosis when evaluating patients with temporal lobe involvement on MRI, lymphocytic pleocytosis and hypoglycorrhachia. Although HSV and autoimmune diseases are the most common causes of limbic encephalitis, as presented in our case, syphilis testing should be considered. <b>Disclosure:</b> Dr. Hu has nothing to disclose. Dr. El Helou has nothing to disclose. Nayrobi Pena Cotui has nothing to disclose. Dr. Balobaid has nothing to disclose. Dr. Montalvo Perero has nothing to disclose.

Mild Encephalopathy with Reversible Splenium Lesion Associated with SARS-CoV-2 Infection (P14-4.007)

<h3>Objective:</h3> NA <h3>Background:</h3> Encephalopathy secondary to SARS-CoV-2 infection has been previously reported, although neuroimaging in many of these patients is typically unremarkable. There are only a few reported cases of patients with SARS-CoV-2 infection associated with mild encephalopathy with a reversible splenial lesion (MERS) on imaging. MERS has a monophasic course of encephalopathy, marginal pleocytosis in the cerebrospinal fluid, and a characteristic MRI finding of a reversible lesion in the splenium of the corpus callosum. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 68-year-old woman presented to the hospital with altered mental status. The patient was found unresponsive during a welfare check at home. Initial neurological evaluation revealed that the patient was awake, alert, and oriented to name and age but not date and time. Speech was fluent with intact naming, repetition, and comprehension. Polymerase chain reaction for SARS-CoV-2 was positive, and history revealed that patient was not vaccinated. CT of the head was unrevealing. MRI of the brain revealed increased signal in the corpus callosum on FLAIR with low diffusivity on diffusion-weighted imaging. The patient was given tocilizumab, dexamethasone, remdesivir, and ceftriaxone to treat superimposed bacterial pneumonia. Encephalopathy improved gradually throughout the hospital course, and the patient was transitioned to an inpatient rehabilitation facility. Repeat brain MRI five weeks from initial imaging showed resolution of the hyperintensity and focus of low diffusivity in the splenium. <h3>Conclusions:</h3> This is a rare case of MERS triggered by SARS-CoV-2 in a patient who presented with encephalopathy. This case expands the clinical spectrum of neurological manifestations associated with SARS-CoV-2 and adds to the already existing literature. Further investigation is imperative for a better understanding of the pathophysiology and management of this entity to avoid unnecessary invasive diagnostic and therapeutic interventions. <b>Disclosure:</b> Dr. Kokash has nothing to disclose. Dr. Reyes has nothing to disclose. Dr. Yacoub has nothing to disclose.

National priority setting partnership using a Delphi consensus process to develop neonatal research questions suitable for practice-changing randomised trials in the UK

BackgroundThe provision of neonatal care is variable and commonly lacks adequate evidence base; strategic development of methodologically robust clinical trials is needed to improve outcomes and maximise research resources. Historically,...

Rickettsial infection‐related encephalitis/encephalopathy with reversible splenial lesion of the corpus callosum

AbstractMild encephalopathy with reversible splenial lesion (MERS) is a rare clinicoradiological entity characterized by a transient mild encephalopathy and MRI findings of a reversible lesion in the splenium of the corpus callosum. Here, we report an atypical case of MERS in a 22‐year‐old woman who presented with 2‐day history of headaches and confusion associated with fever and who completely recovered within 7 days. Exhaustive biological tests panel revealed positive IgM rickettsial antibody, and the final diagnosis was MERS caused by rickettsial infection. Although viruses are the most common pathogen of MERS, for proper management, bacteria should be considered, as they may also lead to this condition.

Management of Hyponatremia in Heart Failure: Practical Considerations.

Hyponatremia is commonly encountered in the setting of heart failure, especially in decompensated, fluid-overloaded patients. The pathophysiology of hyponatremia in patients with heart failure is complex, including numerous mechanisms: increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system, high levels of arginine vasopressin and diuretic use. Symptoms are usually mild but hyponatremic encephalopathy can occur if there is an acute decrease in serum sodium levels. It is crucial to differentiate between dilutional hyponatremia, where free water excretion should be promoted, and depletional hyponatremia, where administration of saline is needed. An inappropriate correction of hyponatremia may lead to osmotic demyelination syndrome which can cause severe neurological symptoms. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The aim of this review is to summarize the principal mechanisms involved in the occurrence of hyponatremia, to present the main guidelines for the treatment of hyponatremia, and to collect and analyze data from studies which target new treatment options, such as vaptans.

Radiomics based of deep medullary veins on susceptibility-weighted imaging in infants: predicting the severity of brain injury of neonates with perinatal asphyxia

ObjectiveThis study aimed to apply radiomics analysis of the change of deep medullary veins (DMV) on susceptibility-weighted imaging (SWI), and to distinguish mild hypoxic-ischemic encephalopathy (HIE) from moderate-to-severe HIE in neonates.MethodsA total of 190 neonates with HIE (24 mild HIE and 166 moderate-to-severe HIE) were included in this study. All of them were born at 37 gestational weeks or later. The DMVs were manually included in the regions of interest (ROI). For the purpose of identifying optimal radiomics features and to construct Rad-scores, 1316 features were extracted. LASSO regression was used to identify the optimal radiomics features. Using the Red-score and the clinical independent factor, a nomogram was constructed. In order to evaluate the performance of the different models, receiver operating characteristic (ROC) curve analysis was applied. Decision curve analysis (DCA) was implemented to evaluate the clinical utility.ResultsA total of 15 potential predictors were selected and contributed to Red-score construction. Compared with the radiomics model, the nomogram combined model incorporating Red-score and urea nitrogen did not better distinguish between the mild HIE and moderate-to-severe HIE group. For the training cohort, the AUC of the radiomics model and the combined nomogram model was 0.84 and 0.84. For the validation cohort, the AUC of the radiomics model and the combined nomogram model was 0.80 and 0.79, respectively. The addition of clinical characteristics to the nomogram failed to distinguish mild HIE from moderate-to-severe HIE group.ConclusionWe developed a radiomics model and combined nomogram model as an indicator to distinguish mild HIE from moderate-to-severe HIE group.

P036: Atypically mild ethylmalonic encephalopathy expands phenotypic spectrum

P036: Atypically mild ethylmalonic encephalopathy expands phenotypic spectrum

Serum magnesium levels of term neonates with birth asphyxia and relationship to severity of asphyxia.

Birth asphyxia is one of the three main causes of neonatal mortality in Nigeria. Hypomagnesaemia has been reported amongst severely asphyxiated babies. Despite this, the prevalence of hypomagnesaemia amongst newborns with birth asphyxia has not been well researched in Nigeria. This study set out to determine the prevalence of hypomagnesaemia in term neonates with birth asphyxia and the relationship (if any) between magnesium levels and the severity of birth asphyxia or encephalopathy. In this cross-sectional analytical study, the serum magnesium levels of consecutive cases of birth asphyxia were compared to that of gestational age-matched healthy term neonates. Babies with Apgar scores <7 in the 5th minute of life were recruited into the study. Blood samples were taken from each baby at birth and 48 h. Serum magnesium was measured using spectrophotometry. Hypomagnesaemia was found in 36 (35.3%) babies with birth asphyxia and 14 (13.7%) healthy controls; this difference was statistically significant (χ2 = 18.098, P = 0.001), with an odds ratio of 3.4 (95% confidence interval = 1.7, 6.9). The median (interquartile range) levels of serum magnesium in babies with mild, moderate and severe asphyxia were 0.7 mmol/L (0.5-1.1), 0.7 mmol/L (0.4-0.9) and 0.7 mmol/L (0.5-1.0), respectively (P = 0.316), while those of babies with mild (stage 1), moderate (stage 2) and severe (stage 3) encephalopathy were 1.2 mmol/L (1.0-1.3), 0.7 mmol/L (0.5-0.8) and 0.8 mmol/L (0.6-1.0), respectively (P = 0.789). This study has shown that hypomagnesaemia was more common in babies with birth asphyxia and there was no relationship between magnesium levels and the severity of asphyxia or encephalopathy.

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

Glucose-to-lactate ratio and neurodevelopment in infants with hypoxic-ischemic encephalopathy: an observational study

We aimed to assess the glucose and lactate kinetics during therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy and its relationship with longitudinal neurodevelopment. We measured glucose and lactate concentrations before TH and on days 2 and 3 in infants with mild, moderate, and severe hypoxic-ischemic encephalopathy (HIE). Neurodevelopment was assessed at 2 years. Participants were grouped according to the neurodevelopmental outcome into favorable (FO) or unfavorable (UFO). Eighty-eight infants were evaluated at follow-up, 34 for the FO and 54 for the UFO group. Severe hypo- (< 2.6 mmol/L) and hyperglycemia (> 10 mmol/L) occurred in 18% and 36% from the FO and UFO groups, respectively. Glucose-to-lactate ratio on day 1 was the strongest predictor of unfavorable metabolic outcome (OR 3.27 pm 1.81, p = 0.032) when adjusted for other clinical and metabolic variables, including Sarnat score.Conclusion: Glucose-to-lactate ratio on day 1 may represent a new risk marker for infants with HIE undergoing TH.What is Known:• Glucose and lactate are key metabolic fuels during neonatal hypoglycemia. This suggests that their concentrations may influence the neurodevelopmental outcome of neonates experiencing hypoxic-hischemic encephalopathy (HIE).What is New:• We describe the relative availbility of glucose and lactate before and during theraputic hypothermia in neonates with HIE.

Cerebral blood flow abnormalities with central sparing on arterial spin labeling in mild encephalopathy associated with excitotoxicity: a case report

BackgroundAcute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL.Case presentationThe patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae.ConclusionsASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.

South African neonates with mild and moderate hypoxic-ischaemic encephalopathy

Background. Clear risk profiles of neonates with mild and moderate hypoxic-ischaemic encephalopathy (HIE) are lacking.Objective. To describe and compare factors associated with mild and moderate HIE in South African neonates.Methods. A prospective, comparative design was used to describe factors among South African neonates with mild (n=13) and moderate (n=33) HIE in an urban tertiary academic hospital. HIE diagnosis and encephalopathy grading were conducted using the modified Sarnat stages. Thompson scores were recorded. Participants’ clinical records were reviewed to identify factors. Descriptive data were obtained. Chi-square and Fisher’s exact tests were used to compare categorical data, and Mann-Whitney tests were used to compare continuous data between groups.Results. Significant differences were found between groups’ admission (p&lt;0.001) and highest Thompson scores (p&lt;0.001). The mild group’s APGAR scores were significantly higher than those of the moderate group at five (p=0.012) and ten minutes (p=0.022). Duration of resuscitation (p=0.011) and time to spontaneous respiration (p=0.012) also differed significantly between groups. Significantly more moderate than mild participants received therapeutic hypothermia (TH) (p&lt;0.001).Conclusion. Clinical tests and management factors differed significantly between groups. The findings provided the multidisciplinary team with an increased understanding of the heterogeneous HIE population and add to existing evidence for identifying neonates eligible for TH in resource-limited settings.

“Mild’’ Hypoxic-Ischaemic Encephalopathy and Therapeutic Hypothermia: A Survey of Clinical Practice and Opinion from 35 Countries

Introduction: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE). Methods: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries. Results: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH. Conclusions: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider “cooling” an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported.

Semi-mechanistic Modeling of Hypoxanthine, Xanthine, and Uric Acid Metabolism in Asphyxiated Neonates.

Previously, we developed a pharmacokinetic-pharmacodynamic model of allopurinol, oxypurinol, and biomarkers, hypoxanthine, xanthine, and uric acid, in neonates with hypoxic-ischemic encephalopathy, in which high initial biomarker levels were observed suggesting an impact of hypoxia. However, the full pharmacodynamics could not be elucidated in our previous study. The current study included additional data from the ALBINO study (NCT03162653) placebo group, aiming to characterize the dynamics of hypoxanthine, xanthine, and uric acid in neonates with hypoxic-ischemic encephalopathy. Neonates from the ALBINO study who received allopurinol or placebo mannitol were included. An extended population pharmacokinetic-pharmacodynamic model was developed based on the mechanism of purine metabolism, where synthesis, salvage, and degradation via xanthine oxidoreductase pathways were described. The initial level of the biomarkers was a combination of endogenous turnover and high disease-related amounts. Model development was accomplished by nonlinear mixed-effects modeling (NONMEM®, version 7.5). In total, 20 neonates treated with allopurinol and 17 neonates treated with mannitol were included in this analysis. Endogenous synthesis of the biomarkers reduced with 0.43% per hour because of precursor exhaustion. Hypoxanthine was readily salvaged or degraded to xanthine with rate constants of 0.5 1/h (95% confidence interval 0.33-0.77) and 0.2 1/h (95% confidence interval 0.09-0.31), respectively. A greater salvage was found in the allopurinol treatment group consistent with its mechanism of action. High hypoxia-induced initial levels of biomarkers were quantified, and were 1.2-fold to 2.9-fold higher in neonates with moderate-to-severe hypoxic-ischemic encephalopathy compared with those with mild hypoxic-ischemic encephalopathy. Half-maximal xanthine oxidoreductase inhibition was achieved with a combined allopurinol and oxypurinol concentration of 0.68 mg/L (95% confidence interval 0.48-0.92), suggesting full xanthine oxidoreductase inhibition during the period studied. This extended pharmacokinetic-pharmacodynamic model provided an adequate description of the complex hypoxanthine, xanthine, and uric acid metabolism in neonates with hypoxic-ischemic encephalopathy, suggesting a positive allopurinol effect on these biomarkers. The impact of hypoxia on their dynamics was characterized, underlining higher hypoxia-related initial exposure with a more severe hypoxic-ischemic encephalopathy status.