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Background: Central nervous system (CNS) tumors are the leading cause of cancer-related deaths in children. While most cases come from low-middle income countries (LMIC) where their prognosis is worse, few epidemiological studies are conducted in these regions., Methods: We conducted a registry-based cohort study for childhood CNS tumors at Children's Cancer Hospital, Egypt (CCHE) over 15 years. Unified treatment protocols are implemented. Survival analyses were conducted using the Kaplan-Meier function. Cases were additionally annotated using the ICCC-3 classification., Results: In total, 5051 children ≤ 18 years old were identified, accounting for 20% of all childhood cancers treated at CCHE. The most common tumor sites were the posterior fossa (36.8%) and the brainstem (17.7%). Pathologies were predominantly astrocytic (n=1360; 26.9%) and embryonal (n=1003; 19.9%) in origin. The 5yr OS and EFS for all cases were 64.6% and 51.8%, respectively. More specifically, 1421 low-grade gliomas were identified, with 5yr OS = 91.1%. Medulloblastoma (n=801) recorded a 5yr OS of 66%. The entity with the worst prognosis was DIPG (n=633) with 5yr OS = 3.2%., Conclusions: We report on a large number of childhood CNS tumors from a LMIC. This study underscores the need to understand the burden of childhood brain tumors and its outcomes in resource-constrained settings., Impact: This study reports on the epidemiology and clinical outcomes of 5000+ children with CNS tumors from a specialized LMIC center. Despite the lack of many sophisticated and advanced facilities, LMIC can improve the clinical end results with experience and augmented efforts.

Purpose: High-grade gliomas in infants and very young children (less than 3 to 5 years old) pose significant challenges due to the limited scientific literature available and high risks associated with treatments. This study aims to investigate their characteristics, treatment, and outcomes., Methods: A cohort study was conducted at Children's Cancer Hospital, Egypt. Cases included children aged < 5 years old with confirmed CNS high-grade glioma. Baseline clinical and radiological characteristics, besides potential prognostic factors were assessed., Results: In total, 76 cases were identified, 7 of them were < 1 year old. Gross- or near-total resection (GTR/NTR) was achieved in 32.9% of all cases. Of the tested cases, H3K27M-alteration was present in 5 subjects only. The 3-year OS and EFS for all cases were 26.9% and 15.4%, respectively. Extent of resection was the most important prognostic factor, as those achieving GTR/NTR experienced more than double the survival compared to those who do not (p = 0.05). Age had a "bimodal" effect on EFS, with those aged 1 to 3 years old faring better than younger and older age groups. Subjects with midline tumors had worse survival compared to non-midline tumors (1-year EFS = 18.5% vs 35%, respectively, p = 0.02)., Conclusion: This study in a large cohort of HGG in infants and very young children offers insights into the characteristics and treatment challenges. Extent of resection, age group, and tumor localization are important prognostic factors. Further research with larger sample size is warranted to refine treatment approaches and improve outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas., Material and Methods: A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare between pure germinoma and other tumor types. Differentially expressed miRNAs were identified. The area under the curve of the receive;r operating characteristic curve was constructed to evaluate diagnostic performance., Results: Samples from 39 pediatric patients were available consisting of 12 pure germinomas and 27 pineal region tumors of other pathologies, including pineal origin tumors [ n = 17; pineoblastoma ( n = 13) and pineal parenchymal tumors of intermediate differentiation ( n = 4)] and others [ n = 10; low-grade glioma ( n = 6) and atypical teratoid rhabdoid tumor ( n = 4)]. Using an adjusted p -value <0.05, three miRNAs showed differential expression (miR-143-3p, miR-320c, miR-320d; adjusted p = 0.0058, p = 0.0478, and p = 0.0366, respectively) and good discriminatory power between the two groups (AUC 90.7%, p < 0.001) with a sensitivity of 25% and a specificity of 100%., Conclusion: Our results suggest that a three-plasma miRNA signature has the potential to non-invasively identify pineal body pure germinomas which may allow selected patients to avoid the potential surgical complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fakhry, Elayadi, Elzayat, Samir, Maher, Taha, El-Beltagy, Refaat, Zamzam, Abdelbaki, Sayed, Kieran and Elhaddad.)

Atypical teratoid rhabdoid tumor (ATRT) is a rare type of potentially fatal childhood brain tumor. The present study aimed to examine the overall survival (OS) and event-free survival (EFS) outcomes of pediatric patients with ATRT and to analyze the impact of different prognostic factors, including age, sex, tumor site and size, metastatic disease, the extent of resection, radiotherapy, and chemotherapy, on survival. The present study included 47 patients with ATRT treated at the Children's Cancer Hospital of Egypt (Cairo, Egypt) between July 2007 and December 2017. These patients were treated according to the Dana-Farber Cancer Institute protocol 02-294 for 51 weeks. Various prognostic factors, including age, sex, tumor size and initial metastatic status, exhibited no impact on the radiological response measured at 6 weeks and at the end of treatment. The primary tumor site significantly affected the response to treatment at 6 weeks (P=0.008). Toxicity-related mortality occurred in 29.8% of patients. The median duration of the treatment protocol was 66.9 weeks. The duration of treatment was in the present cohort was longer than the actual 51 weeks of the protocol due to prolonged supportive care of the included patients. Patients who encountered toxicity received reduced dose of chemotherapy in the subsequent cycles in the protocol. Age, initial metastatic status, tumor site and resection extent did not significantly affect the patient outcomes. Preoperative tumor size significantly affected the EFS (P=0.03) and OS (P=0.04). Radiotherapy administration significantly affected the OS (P<0.001) and EFS (P<0.001). The median EFS and OS of patients were 9.3 and 10.3 months, respectively. A total of 24 (51.1%) patients exhibited disease progression or recurrence. The progression sites were local (n=6), metastatic (n=9) or both local and metastatic (n=9). The results of the present study demonstrated that the therapeutic regimen should be patient-adjusted to maintain the treatment intensity and avoid toxicity-related mortality. In lower middle-income countries, short and intensified induction followed by consolidation of treatment, either by single or tandem autologous stem cell transplant, is needed to avoid prolonged exposure to myelosuppression and toxicity-related mortality., Competing Interests: The authors declare that they have no competing interests., (Copyright: © El-Hemaly et al.)

Background: Posterior fossa tumor is a type of brain tumor that is located at the borders of both the brain stem and cerebellum. The cerebellum is the brain region in charge of balance and coordination. Pediatric patients diagnosed with posterior fossa tumor have been reported to fall frequently., Objectives: The aim of this study is to investigate the effectiveness of balance and coordination training in these children., Methods: This randomized control clinical trial (ClinicalTrials.gov Identifier: NCT04528316) was carried out between September 2020 and April 2021 at Children's Cancer Hospital-57357. The inclusion criteria were patients with posterior fossa tumor in maintenance phase and, age between 5 and 12 years. The exclusion criteria were patients who had a genetic disorder or suffer from mental retardation, a chronic lung disease, severe cardiomyopathy, or a neuromuscular disease that does not relate to tumor. The study participants were randomly assigned into three groups: Group I/Control group: they received Pilates core stability exercises program, Group II/Postural stability group: they received the same program plus HUMAC balance program, and Group III/Coordination group: they received the same program plus coordination exercises of BOT-2. The semi-parametric proportional odds model was used to compare follow-up scores of the Postural stability group vs Control, and Coordination group vs Control, while adjusting for baseline values. All tests were two sided, with alpha set to 0.05., Results: Sixty children including 38 boys and 22 girls were enrolled in this study. In all three groups, postural stability and coordination improved significantly in terms of modified clinical test of sensory integration of balance, center of pressure, limits of stability, bilateral coordination, and upper-limb coordination., Conclusion: The current study supports the value of adding postural stability and coordination training to the physiotherapy plan for children with posterior fossa tumor., Trial Registration Number and Date of Registration: ClinicalTrials.gov Identifier: NCT04528316 on August 27, 2020., (© 2022. The Author(s).)

Aims: To assess the clinical, pathological and molecular characteristics (Sonic hedgehog and group 3/4 molecular subtypes expression) and treatment modalities for infantile medulloblastoma in correlation with outcomes. Materials & methods: A retrospective study of 86 medulloblastoma patients (≤3 years) was conducted. M0 patients <2.5 years received four cycles of chemotherapy followed by focal radiotherapy (FRT) and chemotherapy. Between 2007 and 2015, Metastatic patients <2.5 years received craniospinal irradiation (CSI) after the end of chemotherapy. After 2015, metastatic patients <2.5 years received CSI postinduction. Results: The hazard ratio for death was significantly higher in the FRT (HR = 2.8) group compared with the CSI group (hazard ratio = 1). Metastatic disease significantly affected the overall survival of the Sonic hedgehog group and the overall survival and event-free survival of group 3/4. Conclusion: Metastatic disease had a significant impact on outcomes. FRT is not effective in treating infantile medulloblastoma.

Background: The survival of pineoblastoma patients is low, particularly in infants and those with metastatic disease. This study aimed to analyze the prognostic factors affecting the outcome of Pineoblastoma in different age groups., Methods: A retrospective study included 33 patients. Twenty-two patients older than 3 years had upfront surgery, followed by induction CSI then 6 cycles of chemotherapy. Eleven patients younger than 3 years underwent surgery, followed by induction chemotherapy then radiation therapy. Focal irradiation (54 Gy) was administrated in six patients, and CSI (23.4 Gy) with booster dose 30.6 Gy to the tumor bed in two patients followed by 4 cycles of chemotherapy., Results: Patient's age showed a significant impact on the outcome (P value = 0.001 for EFS and 0.002 for OS). The metastases' presence did not impact the outcome negatively. The survival of patients with metastatic disease did not differ between age groups. However, age had a significant impact on the outcome of M0 disease, with 3-year EFS and OS of 65.3% and 74%, respectively, in the older group compared to 0% for both rates in younger patients. CSI showed a positive impact on survival. For all cases, the 3-year OS and EFS were 46.7% and 44.4%, respectively., Conclusions: A multimodality approach is needed to treat this aggressive disease. Inadequate dose intensity affected our patients' outcome negatively. A more aggressive approach using high-dose chemotherapy or CSI may be required to improve infantile pineoblastoma's dismal outcome. Focal radiotherapy is not an efficacious treatment in infants due to its high-metastatic potential. Molecular typing should be considered to label patients who need a more intensified approach., (© 2021. The Author(s).)

Atomoxetine (ATX) is a noradrenaline reuptake inhibitor used to treat Attention deficit hyperactive disorder (ADHD), or improve cognition in normal subjects. Cancer patients treated with systemic adjuvant chemotherapy have described experiencing deterioration in cognition. Doxorubicin (DOX, Adriamycin) is one of the anthracycline families used in chemotherapy, which has a deteriorating effect on both cognition and proliferation. The cognitive effects of ATX require inputs from the hippocampus. The aim of this study was to examine spatial memory and proliferation in the subgranular zone (SGZ) of the DG in adult Lister Hooded rats treated either alone or with a combination of Atomoxetine (30 mg kg -1  day -1 , six i.p. doses, one injection every other day) and Doxorubicin (DOX) ( 2 mg kg -1  day -1 , six i.p. doses, one injection every other day). Spatial memory was tested using the Novel location recognition (NLR) test, and proliferation of hippocampal cells was quantified using immunohistochemistry for the proliferative marker Ki67. Results showed that ATX treatment has improved the NLR task and increased cell proliferation in the SGZ of the DG, compared with saline-treated controls. Animals treated with DOX only showed deficits in NLR task, and co-administration of ATX along with DOX did not improve their performance. DOX chemotherapy caused a significant reduction in the number of proliferating cells in the SGZ of the DG compared with saline-treated controls. This reduction was reversed by co-administration of ATX. The above findings suggest that DOX can negatively affect both cell proliferation and memory and ATX co-administration improves proliferation, but not memory in the adult male rat hippocampus., (© 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Analysis of fluids in porous media is of great importance in many applications. There are many mathematical models that can be used in the analysis. More realistic models should account for the stochastic variations of the model parameters due to the nature of the porous material and/or the properties of the fluid. In this paper, the standard porous media problem with random permeability is considered. Both the deterministic and stochastic problems are analyzed using the finite volume technique. The solution statistics of the stochastic problem are computed using both Polynomial Chaos Expansion (PCE) and the Karhunen-Loeve (KL) decomposition with an exponential correlation function. The results of both techniques are compared with the Monte Carlo sampling to verify the efficiency. Results have shown that PCE with first order polynomials provides higher accuracy for lower (less than 20%) permeability variance. For higher permeability variance, using higher-order PCE considerably improves the accuracy of the solution. The PCE is also combined with KL decomposition and faster convergence is achieved. The KL-PCE combination should carefully choose the number of KL decomposition terms based on the correlation length of the random permeability. The suggested techniques are successfully applied to the quarter-five spot problem.

Pediatric high-grade gliomas (HGG) are rare aggressive tumors that present a prognostic and therapeutic challenge. Diffuse midline glioma, H3K27M-mutant is a new entity introduced to HGG in the latest WHO classification. In this study we evaluated the presence of H3K27M mutation in 105 tumor samples histologically classified into low-grade gliomas (LGG) (n = 45), and HGG (n = 60). Samples were screened for the mutation in histone H3.3 and H3.1 variants to examine its prevalence, prognostic impact, and assess its potential clinical value in limited resource settings. H3K27M mutation was detected in 28 of 105 (26.7%) samples, and its distribution was significantly associated with midline locations (p-value < 0.0001) and HGG (p-value = 0.003). Overall and event- free survival (OS and EFS, respectively) of patients with mutant tumors did not differ significantly, neither according to histologic grade (OS p-value = 0.736, EFS p-value = 0.75) nor across anatomical sites (OS p-value = 0.068, EFS p-value = 0.153). Detection of H3K27M mutation in pediatric gliomas provides more precise risk stratification compared to traditional histopathological techniques. Hence, mutation detection should be pursued in all pediatric gliomas. Meanwhile, focusing on midline LGG can be an alternative in lower-middle-income countries to maximally optimize patients' treatment options.

The population models allow for a better understanding of the dynamical interactions with the environment and hence can provide a way for understanding the population changes. They are helpful in studying the biological invasions, environmental conservation and many other applications. These models become more complicated when accounting for the stochastic and/or random variations due to different sources. In the current work, a spectral technique is suggested to analyze the stochastic population model with random parameters. The model contains mixed sources of uncertainties, noise and uncertain parameters. The suggested algorithm uses the spectral decompositions for both types of randomness. The spectral techniques have the advantages of high rates of convergence. A deterministic system is derived using the statistical properties of the random bases. The classical analytical and/or numerical techniques can be used to analyze the deterministic system and obtain the solution statistics. The technique presented in the current work is applicable to many complex systems with both stochastic and random parameters. It has the advantage of separating the contributions due to different sources of uncertainty. Hence, the sensitivity index of any uncertain parameter can be evaluated. This is a clear advantage compared with other techniques used in the literature.

Aggresomes are inclusion bodies for misfolded/aggregated proteins. Despite the role of misfolded/aggregated proteins in neurological disorders, their role in cancer pathogenesis is poorly defined. In the current study we aimed to investigate whether aggresomes-positivity could be used to improve the disease subclassification and prognosis prediction of pediatric medulloblastoma. Ninety three pediatric medulloblastoma tumor samples were retrospectively stratified into three molecular subgroups; WNT, SHH and non-WNT/non-SHH, using immunohistochemistry and Multiplex Ligation Probe Amplification. Formation of aggresomes were detected using immunohistochemistry. Overall survival (OS) and event-free survival (EFS) were determined according to risk stratification criteria. Multivariate Cox regression analyses were carried out to exclude confounders. Aggresomes formation was detected in 63.4% (n = 59/93) of samples. Aggresomes were non-randomly distributed among different molecular subgroups (P = 0.00002). Multivariate Cox model identified aggresomes' percentage at ≥20% to be significantly correlated with patient outcome in both OS (HR = 3.419; 95% CI, 1.30-8.93; P = 0.01) and EFS (HR = 3; 95% CI, 1.19-7.53; P = 0.02). The presence of aggresomes in ≥20% of the tumor identified poor responders in standard risk patients; OS (P = 0.02) and EFS (P = 0.06), and significantly correlated with poor outcome in non-WNT/non-SHH molecular subgroup; OS (P = 0.0002) and EFS (P = 0.0004).

Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescents. The epidemiology of these tumors differs in areas of the world. However, very little data is available in the low/middle income countries (LMIC). The aim of this study is to describe the characteristics of primary childhood brain tumors treated at a leading LMIC pediatric cancer hospital and its difference from that in other countries. One thousand one hundred fourteen children and adolescent having CNS tumors were treated in the largest pediatric cancer hospital in the Middle East during a period of 5½ years. They were diagnosed histopathologically in 80.2 %, through medical imaging in 19.4 % and via both tumor markers and imaging in the remaining 0.4 % of cases. Through epidemiological analysis was performed using all available patients' data revealed that 96 % of the patients had primary brain tumors, while only 4 % the primary lesion was in the spinal cord. The most common histological type was astrocytic tumor (30.0 %, pilocytic (GI) = 13.2 %, GII = 10.5 % and GIII + IV (high grade) = 6.3 %) followed by embryonal tumor (23.2 %, medulloblastoma = 18.7 %, PNET = 2.8 %, ATRT = 1.5 % and ependymoblastoma = 0.2 %) then ependymoma in 8.7 %, craniopharyngeoma in 5.3 %. The mean age at diagnosis was 7.1 ± 4.2 years which did not differ significantly by gender nor residency but it differed by the pathological subtype. The frequency of each pathological type was different among different age groups. Though the present study was a hospital-based analysis in a low/middle income country, yet it did not differ from the well-established population-based study reports in the high income countries.

Background: Low grade gliomas are the most common brain tumor in children. Tandem duplication involving the KIAA1549 and the BRAF kinase genes results in a gene fusion that has been recently characterized in a subset of low grade glioma While there is no clear evidence that the KIAA1549-BRAF gene fusion has an effect on prognosis, it is an attractive target for therapy development and as a diagnostic tool., Methods: In the current study we examine the prevalence of KIAA1549-BRAF gene fusion in pediatric patients diagnosed with low grade glioma in the Egyptian population and its relationship to clinical and histological subtypes. Sixty patients between the ages of 1 to 18 years were analyzed for the presence of KIAA1549-BRAF fusion gene products using reverse transcription-PCR and sequencing. The clinicopathologic tumor characteristics were then analyzed in relation to the different fusion genes., Results: KIAA1549-BRAF fusion genes were detected in 56.6% of patients. They were primarily associated with pilocytic astrocytoma (74.2%) and pilomyxoid astrocytoma (60%). Translocation 15-9 was the most common, representing (55.8%) of all positive samples followed by 16-9 (26.4%) and 16-11 (8.8%). Pilocytic astrocytomas presented primarily with 15-9 (32.2%), 16-9 (25.8%) and 16-11 (6.4%) while pilomyxoid astrocytomas presented with 15-9 (46.6%), 16-9 (6.6%) and 16-11 (6.6%) translocations., Conclusion: Gene fusion is found to be significantly increased in cerebellar pilocytic astrocytoma tumors. Furthermore, 15-9 was found to have a higher incidence among our cohort compared to previous studies. While most of the gene fusion positive pilomyxoid astrocytomas were 15-9, we find the association none significant.

Malignant spinal cord compression (MSCC) is a common complication of cancer. Paraspinal neuroblastoma (NB) in the thoracic, abdominal and pelvic regions may extend into the neural foramina causing compression of nerve roots and even the spinal cord. The prompt initiation of specific treatment can improve the neurological outcome. The aim of the present study was to review the clinical features, the management received and the factors that may affect the outcome of patients with MSCC caused by paraspinal NB. During a period between July 2007 and December 2012, a total of 576 NB patients were treated at the Children's Cancer Hospital (Cairo, Egypt). Intraspinal disease extension was present in 51 patients (9%). The children with intraspinal disease extension were reviewed for disease pattern, neurological manifestations and treatment outcome. Children with intraspinal disease extension had an equal male to female ratio (1:1), and approximately two-thirds of patients (34/51) had a clinically manifested cord compression. The duration of neurological manifestations was >4 weeks in 58.8% (20/34) of symptomatic patients and ≤4 weeks in 41.2% (14/34). Subsequent to starting treatment, neurological manifestations showed a complete recovery in 16 patients (47.1%), partial in 11 (32.4%), and stationary course was found in 7 (20.6%). Manifestations of ≤4 weeks in duration carried an improved outcome compared with longer time compression, with a complete recovery in 78.6%, versus 25% for patients with a longer symptom duration (P=0.008). The upfront treatment, patient age and site of the primary tumor did not significantly affect the neurological outcome. Spinal cord compression in NB can be effectively managed with upfront chemotherapy. Initial surgical decompression should be reserved for benign variants only, including ganglioneuroma. Neurological manifestations of <4 weeks duration upon presentation are usually reversible.

Background: To report the authors' experience with recurrent aneurysms after primarily completely clipped cerebral aneurysms and discuss mechanisms of recurrence and recommended management., Methods: Data were available for 1016 consecutive patients who underwent clipping of ruptured and unruptured aneurysms in a 15-year period from 1993-2007., Results: Nine patients were treated for recurrent aneurysms after successful complete clipping of the initial aneurysms; six patients had initial surgery before 1992, and three patients underwent surgery during the study period. Mean elapsed time between the first clipping and the recurrence of aneurysm was 13.3 years ± 7.8. Repeat craniotomy was performed in seven patients, and six patients underwent reclipping of aneurysms with or without removal of the old clips. One patient was treated by construction of an extracranial-intracranial (EC-IC) bypass plus coating of the aneurysm. Endovascular occlusion of the parent artery was performed in one patient. One patient died without any intervention. Recurrent aneurysms could be classified into three types according to the relationship of the new aneurysm neck to the old clip., Conclusions: The incidence of recurrent aneurysms after complete clipping was approximately 0.02% per year; aneurysms recurred after 13.3 years on average with 25 years the longest duration from initial clipping to recurrence. Classification of recurrent aneurysms into three types might be helpful in selecting appropriate surgical management., (Copyright © 2010 Elsevier Inc. All rights reserved.)

5-fluorouracil (5-FU) is a chemotherapeutical agent used to treat cancers including breast and colorectal. Working as an antimetabolite to prevent cell proliferation, it primarily inhibits the enzyme thymidylate synthase blocking the thymidine formation required for DNA synthesis. Although having a relatively short half-life (< 30 mins) it readily enters the brain by passive diffusion. Clinically, it is used both as a single agent or in combination with other chemotherapies and has been associated with the long-term side effects of cognitive impairment, known as "chemo brain" or "chemo fog" These accounts have come primarily from patients undergoing treatment for breast cancer who report symptoms including confusion and memory impairment, which can last for months to years. Psychometric studies of patients have suffered from confounding variables, which has led to the use of rodent models to assess the cognitive effects of this drug. Researchers have used behavioral and physiological tests including the Morris water maze, novel object location/recognition tests, shock motivated T-maze, sensory gating and conditioning, to investigate the effect of this drug on cognition. The variety of cognitive tests and the difference in dosing and administration of 5-FU has led to varied results, possibly due to the different brain regions associated with each test and the subtlety of the drug's effect, but overall these studies indicates that 5-FU has a negative effect on memory, executive function and sensory gating. 5-FU has also been demonstrated to have biochemical and structural changes on specific regions of the brain. Evidence shows it can induce apoptosis and depress cell proliferation in the neurogenic regions of the adult brain including the sub granular zone (SGZ) within the hippocampus and in oligodendrocyte precursor populations within white matter tracts. Furthermore, investigations indicate levels ofdoublecortin, a marker for newly formed neurons and brain derived neurotrophic factor, a cell survival modulator, are also reduced by 5-FU in the SGZ. Thus, 5-FU appears to have a lasting negative impact on cognition and to affect cellular and biochemical markers in various brain regions. Further work is needed to understand the exact mechanisms involved and to devise strategies for the prevention or recovery from these symptoms.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Electroencephalography (EEG) and brain magnetic resonance imaging (MRI) are frequently performed in these infants, but the prognostic value of the combined use of EEG and MRI needs additional exploration. The purpose of this study was to investigate, in neonates with HIE, the role of early EEG and conventional MRI in the prediction of infants at risk for persistent encephalopathy at 18 months of age. Thirty-four term infants with HIE were enrolled in this prospective study. EEG was recorded within the first 72 hours after birth and a brain MRI scan was done between 1 and 4 weeks of age. Denver Developmental Screening Test II was performed at 6, 12, and 18 months of age. Three infants (9%) had mild HIE, 21 infants (62%) had moderate HIE, and 10 infants (29%) had severe HIE. The EEG background was normal, moderately, severely, and extremely discontinuous in eight (24%), three (9%), sixteen (47%), and seven (20%) neonates, respectively. EEG background activities correlated significantly with HIE severity (p = 0.0001). MRI findings significantly correlated with EEG background (p = 0.001). Normal MRI scans and minimal basal ganglia lesions were always associated with normal EEG background. Patients with severe basal ganglia and thalamic lesions in MRI (n = 2) had extreme discontinuous EEG background. For the prediction of poor outcomes, abnormal EEG background activity had a sensitivity (Sn) = 100%, a specificity (Sp) = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 100%, whereas values of abnormal MRI scans were Sn of 100%, Sp = 43%, PPV = 82%, and NPV=100%. EEG background activity is the best element to predict abnormal outcomes. Severe basal ganglia and thalamic injuries on MRI scans are associated with poor outcomes. Otherwise, MRI does not contribute to the prediction of outcomes at 18 months of age.