Neurological Morbidity Research Articles

Inborn errors of metabolism in neonates and pediatrics on varying dialysis modalities: a systematic review and meta-analysis

Abstract Background Some inborn errors of metabolism (IEMs) resulting in aberrations to blood leucine and ammonia levels are commonly treated with kidney replacement therapy (KRT). Children with IEMs require prompt treatment, as delayed treatment results in increased neurological and developmental morbidity. Objectives Our systematic review in neonates and pediatrics evaluates survival rates and reductions in ammonia and leucine levels across different KRT modalities (continuous KRT (CKRT), hemodialysis (HD), peritoneal dialysis (PD)). Data sources A literature search was conducted through PubMed, Web of Science, and Embase databases for articles including survival rate and toxic metabolite clearance data in pediatric patients with IEM undergoing KRT. Study eligibility criteria Cross-sectional, prospective, and retrospective studies with survival rates reported in patients with IEM with an intervention of CKRT, PD, or HD were included. Studies with patients receiving unclear or multiple KRT modalities were excluded. Study appraisal and synthesis methods Analysis variables included efficacy outcomes [% reduction in ammonia (RIA) from pre- to post-dialysis and time to 50% RIA] and mortality. The Newcastle Ottawa Risk of Bias quality assessment was used to assess bias. All statistical analyses were performed with MedCalc Statistical Software version 19.2.6. Results A total of 37 studies (n = 642) were included. The pooled proportion (95% CI) of mortality on CKRT was 24.84% (20.93–29.08), PD was 34.42% (26.24–43.33), and HD 34.14% (24.19–45.23). A lower trend of pooled (95% CI) time to 50% RIA was observed with CKRT [6.5 (5.1–7.8)] vs. PD [14.4 (13.3–15.5)]. A higher mortality was observed with greater plasma ammonia level before CKRT (31.94% for ≥ 1000 µmol/L vs. 15.04% for < 1000 µmol/L). Conclusions and implications of key findings Despite the limitations in sample size, trends emerged suggesting that CKRT may be associated with lower mortality rates compared to HD or PD, with potential benefits including prevention of rebound hyperammonemia and improved hemodynamic control. While HD showed a trend towards faster achievement of 50% RIA, all modalities demonstrated comparable efficacy in reducing ammonia and leucine levels. Prospero registration CRD42023418842. Graphical abstract

K wire migration into spinal canal: An infrequent cause of neurological morbidity: A case report

Introduction: K wire is one of the most common implants used for fixation of acromioclavicular joint dislocation. The migration of K wire from the AC joint to the spinal canal is a rare occurrence. In this report, we present a case of a young adult who presented with weakness of left upper limb secondary to migration of K wire from the AC joint to the spinal canal. Case presentation: A 46-year-old male farmer presented with complaints of pain in the neck, tingling sensation in the left upper limb, and a tender palpable swelling on the left side of his neck with weakness of finger flexors and abductors. He had had an open reduction and fixation with K wire for Acromioclavicular dislocation three months back. CT confirmed the K wire passing through neural foramen between C5 and C6 vertebra and extending across the entire diameter of spinal canal. Under intravenous anesthesia, a transverse skin incision was made over the prominent swelling on the neck and the wire was gently removed. Minimal seepage of spinal fluid was observed which stopped on its own after few days. Discussion: Although AC joint stabilization by K wire fixation provides a safe and easy fixation with low morbidity, complications such as a loss of fixation or loosening can occur. Migration of K wire into a spinal canal is a well-known but infrequent complication. Resorption of bone, muscle action, and negative intrathoracic pressures associated with respiration and heat necrosis causes progressive loosening and dislodgement. Spinal migration is very dangerous because it can cause serious damage to the dura mater, spinal cord, and vertebral artery. Conclusion: Early identification and removal of the K wire, once it has migrated from the site of use, is mandatory to prevent its grievous complications.

Serum proteomics for the identification of biomarkers to flag predilection of COVID19 patients to various organ morbidities

BackgroundCOVID19 is a pandemic that has affected millions around the world since March 2020. While many patients recovered completely with mild illness, many patients succumbed to various organ morbidities. This heterogeneity in the clinical presentation of COVID19 infection has posed a challenge to clinicians around the world. It is therefore crucial to identify specific organ-related morbidity for effective treatment and better patient outcomes. We have carried out serum-based proteomic experiments to identify protein biomarkers that can flag organ dysfunctions in COVID19 patients.MethodsCOVID19 patients were screened and tested at various hospitals across New Delhi, India. 114 serum samples from these patients, with and without organ morbidities were collected and annotated based on clinical presentation and treatment history. Of these, 29 samples comprising of heart, lung, kidney, gastrointestinal, liver, and neurological morbidities were considered for the discovery phase of the experiment. Proteins were isolated, quantified, trypsin digested, and the peptides were subjected to liquid chromatography assisted tandem mass spectrometry analysis. Data analysis was carried out using Proteome Discoverer software. Fold change analysis was carried out on MetaboAnalyst. KEGG, Reactome, and Wiki Pathway analysis of differentially expressed proteins were carried out using the STRING database. Potential biomarker candidates for various organ morbidities were validated using ELISA.Results254 unique proteins were identified from all the samples with a subset of 12–31 differentially expressed proteins in each of the clinical phenotypes. These proteins establish complement and coagulation cascade pathways in the pathogenesis of the organ morbidities. Validation experiments along with their diagnostic parameters confirm Secreted Protein Acidic and Rich in Cysteine, Cystatin C, and Catalase as potential biomarker candidates that can flag cardiovascular disease, renal disease, and respiratory disease, respectively.ConclusionsLabel free serum proteomics shows differential protein expression in COVID19 patients with morbidity as compared to those without morbidity. Identified biomarker candidates hold promise to flag organ morbidities in COVID19 for efficient patient care.

Staged intervention to enable the resection of a large left temporoinsular cystic glioblastoma with language preservation: illustrative case.

Resection of glioblastoma (GBM) in eloquent regions depends on functional mapping to limit perioperative neurological morbidity. When neurological deficits preclude reliable mapping, neurosurgeons should explore potential mitigation strategies. The authors present the case of a patient with a large left cystic temporoinsular GBM and aphasia, for whom the authors used intraoperative language mapping and a staged approach to enable safe tumor resection. A 49-year-old female presented with progressive mixed aphasia for 1 month and new-onset right facial droop. Magnetic resonance imaging (MRI) revealed a large, heterogeneously enhancing, left temporoinsular tumor with a significant cystic component. Her aphasia was profound, and resection without reliable language mapping was deemed unsafe. An initial stereotactic tumoral cyst aspiration was performed, which reduced local mass effect and improved her language function. Cyst decompression thereby enabled both task-based functional MRI and intraoperative awake speech mapping, resulting in a safe resection of her GBM. Safe resection of eloquently localized GBM is compromised when neurological deficits prohibit intraoperative functional mapping. This case demonstrates a mitigation strategy specific to cystic lesions in which an initial-stage stereotactic cyst aspiration is aimed at generating sufficient interval neurological improvement, such that intraoperative functional mapping can be performed during a second-stage resection. https://thejns.org/doi/10.3171/CASE24362.

Enriching Clinical Trials Enrolling Children With Cerebral Malaria Using Admission Demographics, Physical Examination and Point-of-care Testing Results.

Multiple clinical trials evaluating therapies for cerebral malaria (CM) have failed to demonstrate improved outcomes. This may derive from inclusion of children at all risk levels, including those at low risk of mortality or neurologic morbidity, limiting power to detect significant differences between intervention arms. One solution is enrichment, enrolling clinical trial participants at higher risk of adverse outcomes. We assessed if demographic, physical examination and point-of-care laboratory testing results in combination could identify children with CM at higher risk of death or neurologic disability. Retrospective case-control study of 1674 children hospitalized with CM in Blantyre, Malawi. We used univariate and multivariate analyses of admission factors to find the most parsimonious model associated with death or neurologic disability. To assess the clinical utility of the models, we evaluated derived probability density curve separation. Blantyre Coma Score (BCS), deep breathing and high blood lactate were independently associated with mortality. The derived receiver operating curve yielded an area under the curve of 0.7118. There was poor separation of derived probability density curves predicting death or survival, indicating limited clinical utility of this model. On multivariate modeling of neurologic sequelae in CM survivors, only BCS was associated with adverse outcomes (area-under-the-curve = 0.6151). Probability density curves again largely overlapped, demonstrating limited utility of BCS alone in outcome prediction. Combinations of admission demographic, clinical and point-of-care laboratory factors are inadequate to predict prognosis in children with CM. Higher technology assessment methods are necessary for clinical trial enrichment.

Structural development and brain asymmetry in the fronto-limbic regions in preschool-aged children.

Early-life experiences play a crucial role in the development of the fronto-limbic regions, influencing both macro- and microstructural changes in the brain. These alterations profoundly impact cognitive, social-emotional functions. Recently, early limbic structural alterations have been associated with numerous neurological and psychiatric morbidities. Although identifying normative developmental trajectories is essential for determining brain alterations, only a few studies have focused on examining the normative trajectories in the fronto-limbic regions during preschool-aged children. The aim of this study was to investigate the structural-developmental trajectory of the fronto-limbic regions using the cortical thickness, volume, and subcortical volume in 57 healthy and typical preschool-aged children between 1 and 5 years and examined the early lateralization patterns during the development of the fronto-limbic regions. Regarding brain lateralization, remarkable asymmetry was detected in the volume of thalamus and the cortical regions excluding the lateral orbitofrontal cortex in the fronto-limbic regions. This study of preschool-aged children may fill the knowledge gaps regarding the developmental patterns and hemispheric asymmetries of the fronto-limbic regions between newborns and adolescents.

Clinical profile of patients with surgical brain abscesses and etiology in a reference hospital.

The annual incidence of brain abscesses is 1-2% in developed countries and up to 8% in developing countries. Our aim was to describe the profile and etiological agents of patients with surgical brain infections according to their nosological diagnosis on admission, and to analyze whether the initial diagnosis influenced the neurological deficit at discharge. This was an observational study with convenience sampling. All surgical cases operated between January 2017 and February 2022 with a final diagnosis of an infectious process were included. Three groups were analyzed according to admission diagnosis: a) infection, b) neoplasia, and c) miscellaneous. The time before admission, final histological diagnosis, etiological agent, length of hospital stay, and secondary neurological deficits were investigated. Descriptive and comparative statistics were used. 24 cases, including 18 (75%) men and 6 (25%) women, of ages 19 to 61 years (average 43.7 years) were studied. Nosological diagnoses on admission were infection in 9 (37.5%) patients, cerebral neoplasia in 9 (37.5%) patients, and miscellaneous diagnoses in 6 (25%) patients. Among the miscellaneous, neoplastic, and infectious groups, 33.3%, 33.3%, and 22.2% of patients were discharged with some neurological deficits with overall neurological morbidity and mortality of 29.6% and 8%, respectively. The etiological agents were Mycobacterium tuberculosis (16.6%), Streptococcus sp. (13%), Morganella morganii (8.7%), Nocardia sp. (4.3%), Cryptococcus sp. (4.3%), and Klebsiella sp. (4.3%). Nosological diagnosis on admission did not influence the percentage of patients with neurological deficits in our study. Mycobacterium was the most frequent etiological agent.

Development, External Validation, and Biomolecular Corroboration of Interoperable Models for Identifying Critically Ill Children at Risk of Neurologic Morbidity.

Declining mortality in the field of pediatric critical care medicine has shifted practicing clinicians' attention to preserving patients' neurodevelopmental potential as a main objective. Earlier identification of critically ill children at risk for incurring neurologic morbidity would facilitate heightened surveillance that could lead to timelier clinical detection, earlier interventions, and preserved neurodevelopmental trajectory. Develop machine-learning models for identifying acquired neurologic morbidity while hospitalized with critical illness and assess correlation with contemporary serum-based, brain injury-derived biomarkers. Retrospective cohort study. Two large, quaternary children's hospitals. Critical illness. The outcome was neurologic morbidity, defined according to a computable, composite definition at the development site or an order for neurocritical care consultation at the validation site. Models were developed using varying time windows for temporal feature engineering and varying censored time horizons prior to identified neurologic morbidity. Optimal models were selected based on F1 scores, cohort sizes, calibration, and data availability for eventual deployment. A generalizable created at the development site was assessed at an external validation site and optimized with spline recalibration. Correlation was assessed between development site model predictions and measurements of brain biomarkers from a convenience cohort. After exclusions there were 14,222-25,171 encounters from 2010-2022 in the development site cohorts and 6,280-6,373 from 2018-2021 in the validation site cohort. At the development site, an extreme gradient boosted model (XGBoost) with a 12-hour time horizon and 48-hour feature engineering window had an F1-score of 0.54, area under the receiver operating characteristics curve (AUROC) of 0.82, and a number needed to alert (NNA) of 2. A generalizable XGBoost model with a 24-hour time horizon and 48-hour feature engineering window demonstrated an F1-score of 0.37, AUROC of 0.81, AUPRC of 0.51, and NNA of 4 at the validation site. After recalibration at the validation site, the Brier score was 0.04. Serum levels of the brain injury biomarker glial fibrillary acidic protein measurements significantly correlated with model output (r s =0.34; P =0.007). We demonstrate a well-performing ensemble of models for predicting neurologic morbidity in children with biomolecular corroboration. Prospective assessment and refinement of biomarker-coupled risk models in pediatric critical illness is warranted. Question Can interoperable models for predicting neurological deterioration in critically ill children be developed, correlated with serum-based brain-derived biomarkers, and validated at an external site? Findings A development site model demonstrated an area under the receiver operating characteristics curve (AUROC) of 0.82 and a number needed to alert (NNA) of 2. Predictions correlated with levels of glial fibrillary acidic protein in a subset of children. A generalizable model demonstrated an AUROC of 0.81 and NNA of 4 at the validation site. Meaning Well performing prediction models coupled with brain biomarkers may help to identify critically ill children at risk for acquired neurological morbidity.

Resuscitation arterial waveform quantification and outcomes in pediatric bidirectional Glenn and Fontan patients.

Resuscitation with chest compressions and positive pressure ventilation in Bidirectional Glenn (BDG) or Fontan physiology may compromise passive venous return and accentuate neurologic injury. We hypothesized that arterial pressure and survival would be better in BDG than Fontan patients. Secondary analyses of the Pediatric Intensive Care Quality of CPR and Improving Outcomes from Pediatric Cardiac Arrest databases. P-values were considered significant if < 0.05. In total, 64 patients had either BDG (42/64, 66%) or Fontan (22/64, 34%) anatomy. Return of spontaneous circulation was achieved in 76% of BDG patients versus 59% of Fontan patients and survival with favorable neurologic outcome in 22/42 (52%) BDG versus 6/22 (27%) Fontan patients, p = 0.067. Twelve of 24 (50%) BDG and 2/7 (29%) Fontan patients who survived to discharge suffered new morbidity as defined by worsening Functional Status Score. More BDG patients achieved adequate DBP (≥25 mmHg for neonates and infants; ≥ 30 mmHg for children) than Fontan patients (21/23 (91%) vs. 5/11 (46%), p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after CPR, likely driven by inadequate diastolic blood pressure during resuscitation. One half of the BDG patients who survived to hospital discharge had new neurologic morbidity. Cardiac arrest in patients with congenital heart disease (CHD) may present challenges to resuscitation based on the unique cardiovascular physiology resulting from surgical palliation. Recent resuscitation guidelines for CHD patients highlight the lack of data surrounding these special patient populations.1 Univentricular heart disease is palliated by a series of cardiac surgeries that stepwise result in passive pulmonary perfusion from the systemic venous system directly to the pulmonary vascular bed. The bidirectional Glenn (BDG) palliation directly anastomoses the superior vena cava (SVC) to the pulmonary arterial system and leaves normal inferior vena cava (IVC) venous return to the heart.2 The Fontan palliation baffles IVC flow directly to the pulmonary vascular bed which relieves cyanosis due to right to left shunting, but requires systemic ventricular preload to be directly dependent upon pulmonary vascular resistance and intrathoracic pressures.3 IMPACT STATEMENT: Hemodynamic waveforms from 2 large prospective observational studies now allow for exploration of physiology during cardiopulmonary resuscitation for unique anatomy associated with single ventricle congenital heart disease. Fewer patients with Fontan physiology (46%) achieved an adequate diastolic blood pressure (defined as ≥ 25 mmHg for neonates and infants and ≥ 30 mmHg for children) than bidirectional Glenn patients during cardiopulmonary resuscitation (91%, p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after cardiopulmonary resuscitation. Of the bidirectional Glenn patients who survived, 50% developed a new morbidity as quantified by the Functional Status Score.

Initial Experience with the New DERIVO® Mini Embolisation Device for the Treatment of Intracranial Aneurysms.

The aim of this study is to present the outcomes of cerebral aneurysm treatment with the DERIVO® mini Embolisation Device (DMD), which is compatible with microcatheters with 0.021-inch inner diameters. Consecutive patients treated with DMD were identified retrospectively. Patient and aneurysm characteristics, procedural findings, clinical outcomes and follow-up imaging results were evaluated. A total of 44 target aneurysms in 30 patients were treated with DMD. The mean age of the patients was 49.9 (range, 4-77 years). Four patients with five aneurysms presented with acute subarachnoid hemorrhage. The mean aneurysm size was 6.8 mm (range, 1.5-22 mm). In 29 (65.9%) aneurysms, adjunctive devices were used for endovascular treatment. The overall mortality rate was 3.3% and procedure-related mortality was 0%. Overall neurologic morbidity was 6.6% and none of the patients had a permanent sequela secondary to the procedure. The mean clinical follow-up period was 20.9 months (range, 3 days-46 months) and the mean DSA follow-up period was 10.9 months. A total of 37 (84.1%) aneurysms demonstrated total occlusion (Raymond-Roy [RR 1]); 3 (6.8%) aneurysms had a neck remnant or infundibular filling at the origin of the jailed side branch (RR 2), 4 (9.1%) aneurysms had residual aneurysm filling (RR 3). For those aneurysms treated with bare DMD, the total occlusion rate was 73.3% at a mean follow-up of 16.1 months. In this initial clinical single-center experience, DMD had a good safety profile and efficacy comparable with the currently used flow diverters.

Elizabethkingia meningoseptica: A Rare Cause of Infection in Neonates

Elizabethkingia meningoseptica is known to cause nosocomial infection, particularly among preterm neonates, causing high rates of mortality and significant neurological morbidity amid survivors. The disease presents several challenges in diagnosis and management due to its rarity and multidrug resistance. With the increasing incidence of preterm births in Middle East; and consequently, prolonged NICU admissions and hospital acquired infections, it is essential for the physicians to have knowledge on diagnostic and therapeutic strategies about an organism that could possibly affect such infants and cause devastating outcomes. Our study’s primary objective is to give neonatologists a comprehensive overview of E.meningoseptica with its presenting features, risk factors, diagnostic modalities, management protocols and complications. We conducted a literature search on E.meningoseptica infection in neonates, and included a total of 19 reports of this disease, published between 2018-2023 in our study. The cases we reviewed consisted of both preterm and term neonates showing various presentations of the infection with the most common being meningitis. Rapid diagnosis through blood and CSF cultures or utilizing automated systems, together with the initiation of appropriate combination antibiotic therapy is indispensable. In addition, practicing rigorous infection control policies, and having a high index of suspicion when dealing with cases of neonatal sepsis and/ or meningitis is the cornerstone of management.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Bilateral antegrade cerebral perfusion during hypothermic circulatory arrest before sternal reentry for aortic pseudoaneurysm repair.

Sternal reentry for repair of aortic pseudoaneurysms poses a unique technical challenge to prevent exsanguination. Initiation of peripheral cardiopulmonary bypass and deep hypothermic circulatory arrest prior to reentry are the cornerstones of a successful surgical approach. Adjunctive bilateral antegrade cerebral perfusion increases safe arrest time and reduces neurologic morbidity. Herein, we describe our safe reentry technique for aortic pseudoaneurysm repair in two patients.

Pott's puffy tumor with intracranial extension in a child with incontinentia pigmenti: case based review of the eponymous disease.

Pott's puffy tumor (PPT) is an uncommon infection involving the frontal bone, first described by Sir Percival Pott more than 250years ago. It can present with intracranial extension and serious neurological morbidity. Incontinentia pigmenti (IP) is a rare inherited genodermatosis that is lethal prenatally in males and manifests clinically in females. IP is associated with recurrent infections and immune dysfunction/suppression. We report a case of Pott's puffy tumor presenting in a child with IP. We also performed a literature review of reported cases of PPT associated with immune dysfunction. We discuss the clinical presentation, diagnosis, and management of these lesions. We identified 12 cases of PPT associated with immune dysfunction/suppression. Diabetes was the most commonly identified cause followed by iatrogenic immunosuppression. Surgery is the standard treatment for managing PPT and the management of PPT with and without intracranial involvement, particularly in the context of underlying immune dysfunction/suppression, is discussed. PPT remains a rare but not infrequent diagnosis, often requiring neurosurgical intervention. Immune dysfunction/suppression is an additional risk factor that may predispose to PPT. Early and aggressive management should be instituted for optimal outcome.

The DERIVO2 Heal Embolization Device in the Treatment of Ruptured and Unruptured Intracranial Aneurysms: aRetrospective Multicenter Study.

The use of flow diverting stents in the treatment of intracranial aneurysms is associated with arisk of neurological morbidity due to their thrombogenicity. To reduce this risk different surface modifications have been developed. The Derivo2 Embolization Device (Acandis, Pforzheim, Germany) has proven to be asafe and effective flow diverter. To overcome the risk of thrombo-embolism, the device was modified by adding an anti-thrombogenic fibrin-heparin coating. We aimed to assess the safety and effectiveness of the Derivo2 heal Embolization Device. Retrospective multicenter data from nine German neurovascular centers between February 2022 until December 2023 were used. Patients treated with the Derivo2 heal Embolization Device for unruptured or ruptured intracranial aneurysms were included. Peri- and postprocedural adverse events, clinical outcomes, and angiographic follow-up results were evaluated. 84patients (73.8% female; mean age58.7 years) with 89aneurysms (mean size 9.8 mm) were included. 87.6% were located in the anterior circulation. Most of them were sidewall aneurysms (88.8%). 96flow diverters were used. 99.0% were successfully implanted. An in-stent balloon angioplasty was performed in 6.0% of the cases. An additional coiling was performed in 28.6%. Technical difficulties were present in 12.0% of the cases. Thrombotic events occurred in 4.8% with no neurological sequelae. Mortality and morbidity were 0 and 1.2% respectively. Adequate aneurysm occlusion was achieved in 80.7% with amean follow-up time of 6.6months. The Derivo2 heal Embolization Device showed asatisfying aneurysm occlusion and safety with alow rate of neurological morbidity.

Prolonged extracellular low sodium concentrations and subsequent their rapid correction modulate nitric oxide production dependent on NFAT5 in microglia

Hyponatremia is the most common clinical electrolyte disorder. Chronic hyponatremia has been recently reported to be associated with falls, fracture, osteoporosis, neurocognitive impairment, and mental manifestations. In the treatment of chronic hyponatremia, overly rapid correction of hyponatremia can cause osmotic demyelination syndrome (ODS), a central demyelinating disease that is also associated with neurological morbidity and mortality. Using a rat model, we have previously shown that microglia play a critical role in the pathogenesis of ODS. However, the direct effect of rapid correction of hyponatremia on microglia is unknown. Furthermore, the effect of chronic hyponatremia on microglia remains elusive. Using microglial cell lines BV-2 and 6-3, we show here that low extracellular sodium concentrations (36 mmol/L decrease; LS) suppress Nos2 mRNA expression and nitric oxide (NO) production of microglia. On rapid correction of low sodium concentrations, NO production was significantly increased in both cells, suggesting that acute correction of hyponatremia partly directly contributes to increased Nos2 mRNA expression and NO release in ODS pathophysiology. LS also suppressed expression and nuclear translocation of nuclear factor of activated T cells-5 (NFAT5), a transcription factor that regulates the expression of genes involved in osmotic stress. Furthermore, overexpression of NFAT5 significantly increased Nos2 mRNA expression and NO production in BV-2 cells. Expressions of Nos2 and Nfat5 mRNA were also modulated in microglia isolated from cerebral cortex in chronic hyponatremia model mice. These data indicate that LS modulates microglial NO production dependent on NFAT5 and suggest that microglia contribute to hyponatremia-induced neuronal dysfunctions.

Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer's disease-related genes in mice

Hypoxic-ischemic encephalopathy (HIE) in neonates causes mortality and neurologic morbidity, including poor cognition with a complex neuropathology. Injury to the cholinergic basal forebrain and its rich innervation of cerebral cortex may also drive cognitive pathology. It is uncertain whether genes associated with adult cognition-related neurodegeneration worsen outcomes after neonatal HIE. We hypothesized that neocortical damage caused by neonatal HI in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer's disease. We subjected non-transgenic (nTg) C57Bl6 mice and mice transgenically (Tg) expressing human mutant amyloid precursor protein (APP-Swedish variant) and mutant presenilin (PS1-ΔE9) to the Rice-Vannucci HI model on postnatal day 10 (P10). nTg and Tg mice with sham procedure were controls. Visual discrimination (VD) was tested for cognition. Cortical and hippocampal cholinergic axonal and IN pathology and Aβ plaques, identified by immunohistochemistry for choline acetyltransferase (ChAT) and 6E10 antibody respectively, were counted at P210. Simple ChAT+ axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings in APP/PS1 Tg mice. In contrast, complex ChAT+ neuritic clusters (NC) occurred only in Tg mice; HI increased that burden. The abundance of ChAT+ clusters in specific regions correlated with decreased VD. The frequency of attritional ChAT+ INs in the entorhinal cortex (EC) was increased in Tg shams relative to their nTg counterparts, but HI obviated this difference. Cholinergic IN pathology in EC correlated with NC number. The Aβ deposition in APP/PS1 Tg mice was not exacerbated by HI, nor did it correlate with other metrics. Adult APP/PS1 Tg mice have significant cortical cholinergic axon and EC ChAT+ IN pathologies; some pathology was exacerbated by neonatal HI and correlated with VD. Mechanisms of neonatal HI induced cognitive deficits and cortical neuropathology may be modulated by genetic risk, perhaps accounting for some of the variability in outcomes.

Small for gestational age in twin pregnancies and the risk of offspring pediatric neurologic morbidity.

Small for gestational age (SGA) singletons are at increased risk for neurodevelopmental abnormalities. Scarce data exist regarding the long-term implications of SGA in twins. We opted to study the association between SGA of one twin and long-term neurologic related morbidity in dichorionic diamniotic twins. A population-based retrospective cohort study including consecutive dichorionic diamniotic twins, born between the years 1991 and 2021 at a tertiary medical center was conducted. Total and subtypes of neurologic related pediatric hospitalizations among SGA versus non-SGA twins were compared. A Kaplan-Meier survival curve was used to compare the cumulative neurologic morbidity incidence, and a Cox proportional hazards model was constructed to adjust forconfounders. The study population included 4222 newborns; 180 (4.3%) were SGA. Rate of long-term neurologic related hospitalizations was comparable between the two groups (8.7 vs. 8.0%, p = 0.755; Kaplan-Meier survival curve Log-rank p = 0.652). Using a Cox proportional hazards model, controlling for gender and birth order, no association was found between SGA and the risk for subsequent neurologic pediatric morbidity of the offspring (Adjusted HR = 1.0, 95% CI 0.6-1.8, p = 0.973). SGA is not associated with an increased risk for long-term pediatric neurologic morbidity in dichorionic diamniotic twins.

Plama Osmolality Status in Acute Stroke Patients and in Healthy Individuals in Rajshahi Medical College Hospital

Background: Stroke is the most prevalent neurological emergency and accounts for approximately 50% of all neurological disorders in medical college hospitals. It is the leading cause of adult neurological morbidity and the third leading cause of death globally. Changes in plasma osmolality are associated with increased complications, mortality, morbidity, and disability in stroke patients. Objective: This study aims to investigate the changes in plasma osmolality in different types of acute stroke patients and its impact on stroke outcomes. Method: The study included two groups: Group I comprised 104 acute stroke patients (mean age 58.87±13.70) as cases, and Group II consisted of 104 age- and sex-matched healthy individuals (mean age 57.55±12.60) as controls. Each stroke patient underwent cranial computed tomography within the first 24 hours. Blood tests for blood sugar, serum electrolytes, lipid profile, and blood urea were performed. The CT findings and pathological test results were analyzed using SPSS software. Result: Among the 104 stroke patients, 71 (68.27%) had ischemic stroke, and 33 (31.73%) had hemorrhagic stroke. Dyselectrolytaemia was observed in 73 (70.20%) of the stroke patients, while 31 (29.80%) had normal electrolyte levels. Hyperosmolality was present in 58 (55.77%) of the patients, and hypoosmolality was found in 3 (2.88%). Conclusions: Abnormal plasma osmolality is a significant independent risk factor for complications in acute stroke patients, both ischemic and hemorrhagic. Plasma osmolality estimation should be considered a crucial clinical investigation for evaluating acute stroke patients in the early stages.

Intracranial complications secondary to acute bacterial sinusitis requiring neurosurgical intervention before and after the onset of the COVID-19 pandemic.

Intracranial complications of acute bacterial sinusitis are rare pathologies that occur in children, and are associated with significant neurological morbidity and mortality. There is a subjective concern among neurosurgeons that the incidence of this rare disease has increased since the onset of the novel COVID-19 pandemic. The primary objective of this study was to review the presentation and management of patients admitted at the authors' institution with intracranial extension of sinusitis, to better understand the local disease burden relative to the COVID-19 pandemic. This is a single-center retrospective observational cohort study. The patients underwent neurosurgical intervention for intracranial extension of sinusitis between January 1, 2007, and March 1, 2023. The historical cohort was defined as those patients who presented prior to March 2020. Clinical covariates such as surgical and microbiological data were collected and analyzed. A total of 78 patients (55 historical, 23 new) were included; they had a median age of 11.7 years and a male predominance of 69.2%. There was a significant increase in the annual rate of neurosurgical intervention for suppurative intracranial extension of acute bacterial sinusitis after the onset of the COVID-19 pandemic, with an average of 4.2 cases per year prior to March 2020 compared to 7.7 cases per year after that date (p = 0.013). This increase was largely driven by the unprecedented case volume of 13 cases in 2022. Patients in the new cohort were older (p = 0.009) and more likely to have Pott's puffy tumor/frontal bone osteomyelitis (p = 0.003) at the time of presentation than patients in the historical cohort. Patients in the new cohort had lower rates of readmission within 30 days of discharge than those in the historical cohort (p = 0.047). In both cohorts, patients with seizure on presentation were more likely to have neurological sequelae at last follow-up (p = 0.004), which occurred at a median of 2.9 months after discharge. Clinicians encountering pediatric patients presenting with persistent symptoms of acute bacterial sinusitis must have a high index of suspicion for suppurative intracranial extension. Prompt neuroimaging and subsequent neurosurgical intervention are critical to ensure timely diagnosis and treatment. The results in this study show a significant increase in the number of neurosurgical interventions for suppurative intracranial extension of sinusitis per year after the onset of the COVID-19 pandemic. Further research is needed to understand the underlying pathophysiology of this clinical phenomenon.