Neurological Sequelae Research Articles

An online calculator using machine learning for predicting survival in pediatric patients with medulloblastoma.

Medulloblastoma is the most common malignant intracranial tumor affecting the pediatric population. Despite advancements in multimodal treatment over the past 2 decades yielding a 5-year survival rate > 75%, children who survive often have substantial neurological and cognitive sequelae. The authors aimed to identify risk factors and develop a clinically friendly online calculator for prognostic estimation in pediatric patients with medulloblastoma. Pediatric patients with a histopathologically confirmed medulloblastoma were extracted from the Surveillance, Epidemiology, and End Results database (2000-2018) and split into training and validation cohorts in an 80:20 ratio. The Cox proportional hazards model was used to identify the univariate and multivariate survival predictors. Subsequently, a calculator with those factors was developed to predict 2-, 5-, and 10-year overall survival as well as median survival months for pediatric patients with medulloblastoma. The performance of the calculator was determined by discrimination and calibration. One thousand seven hundred fifty-nine pediatric patients with medulloblastoma met the prespecified inclusion criteria. Age, sex, race, ethnicity, median household income, county attribute, laterality, anatomical location, tumor grade, tumor size, surgery status, radiotherapy, and chemotherapy were variables included in the calculator (https://spine.shinyapps.io/Peds_medullo/). The concordance index was 0.769 in the training cohort and 0.755 in the validation cohort, denoting clinically useful predictive accuracy. Good agreement between the predicted and observed outcomes was demonstrated by the calibration plots. An easy-to-use prognostic calculator for a large cohort of pediatric patients with medulloblastoma was established. Future efforts should focus on improving granularity of population-based registries and externally validating the proposed calculator.

Loss to Hospital Follow-Up in Pediatric Cerebral Malaria Survivors: A Case-Control Study.

Children surviving central nervous system (CNS) infections are at high risk of neurological, behavioral, and cognitive sequalae. Early identification, characterization, and treatment of these sequelae may improve child and family health. In Africa, it is unclear if there are demographic or clinical factors that increase the risk of post-hospital loss to follow-up in children with CNS infections. If these factors exist, targeted educational efforts to increase rates of post-hospital retention could be focused on families at highest risk. We performed a case-control study of Malawian children with cerebral malaria, a locally common CNS infection, previously admitted to a specialized research unit in Blantyre, Malawi. Routine survivor post-hospital follow-up was scheduled for 1 month, 6 months, and 12 months. We compared demographic and clinical characteristics between 84 children who missed one or more of these post-hospital visits with 120 children who attended all visits. There were no statistically significant differences in demographic or clinical characteristics between children whose families returned for all follow-up visits and those who did not. Specifically, when comparing these groups, we found no differences in age (P = 00.646), sex (P = 0.789), duration of hospitalization (P = 0.903), distance from home to hospital (P = 0.355), type or severity of neurological sequelae (P = 0.837), guardian literacy (P = 0.057), or number of discharge medications (P = 0.464). No factors assessed in this study were associated with higher risk of loss to follow-up in Malawian child survivors of CNS infections. During hospitalization, educational efforts to increase post-hospital retention should focus on all families.

Selective inhibition of soluble TNF using XPro1595 improves hippocampal pathology to promote improved neurological recovery following traumatic brain injury in mice.

To determine the efficacy of XPro1595 to improve pathophysiological and functional outcomes in a mouse model of traumatic brain injury (TBI). Symptoms associated with TBI can be debilitating, and treatment without off-target side effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI. Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation and dendritic plasticity, and associated functional impairments. Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically relevant window (60 minutes post-injury). The animals were assessed for differences in neurological function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as neuronal degeneration and plasticity. We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology's within the hippocampus consistent with the observed neurological outcomes, including glial reactivity, enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity (spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were prevented in mice treated with XPro1595. Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use in patients with TBI.

14 Title: Design of a neuropsychological battery for the detection of cognitive deficits in asymptomatic patients with low-grade glioma: a pilot study

Objective:Gliomas are a group of CNS neoplasms arising from neuroglial cells with various degrees of aggressiveness. Resection of brain tumors is complex to perform without neurological sequelae due to the diffuse nature of the tumors. This study aimed to design a neuropsychological battery to examine pre surgical cognitive deficits in a case series of patients with LGG and to determine the post-surgical effects after resection.Participants and Methods:11 adult patients aged 19-65 years (38 ±DS:15.5) with a diagnosis of LGG without cognitive complaint were evaluated with a selection of specific neuropsychological tests to identify possible baseline cognitive deficits and their evolution after tumor resection. All participants completed a comprehensive neuropsychological evaluation assessing memory, language, attention, executive functions, visuospatial functions, social cognition, praxis, agnosias, functionality, mood, and quality of life. The neuropsychological battery design was based on a systematic review of the literature on surgical interventions in low-grade gliomas.Results:Despite not reporting subjective cognitive complaints, patients showed deficits in multiple cognitive domains in the pre-surgical evaluation when comparing their performance with normative values adjusted for age, sex, and education. Deficits in executive functions and attention were observed: 36% presented failures in graphomotor speed (TMT A), 27% of subjects presented failures in attentional span (Direct Digit Span), working memory (Inverse Digit Span), and cognitive flexibility (Wisconsin Card Sorting Test) and 9% presented difficulties in processing speed (Trail Making Test A) and inhibitory capacity (Stroop Test). Memory: 18% of the patients showed deficits in immediate logical memory and 9% in delayed memory (Craft Story 21). Likewise, 18% of the patients presented compromise in immediate auditory-verbal learning and 27% in delayed auditory-verbal learning (Rey Auditory-Verbal Test). Language: 18% showed failures in naming (Boston 60) and 9% in comprehension (Token Test). Likewise, 27% of the patients presented difficulties in social cognition (Mind in the Eyes Test). Finally 41% of the patients reported symptoms of depression and/or anxiety in the neuropsychiatric questionnaires.Conclusions:The results highlight the importance of strategically designed pre-surgical cognitive assessment for the detection and follow-up of cognitive and mood disorders associated with the location of the space-occupying lesion (LOE). The patients assessed in this study will be evaluated three months after surgery to document changes in baseline cognitive symptoms. Furthermore, in patients with lesions in the left hemisphere, an intraoperative evaluation will be performed to minimize subsequent deficits, assessing these functions during surgery and emphasizing language.

48 A Case of an Extremely Rare CNS C. Bantiana Infection with Cognitive Sequela in an Immunocompetent Patient

Objective:Central nervous system (CNS) infections with the dematiaceous fungus Cladophialophora bantiana (C. bantiana) are extremely rare, with approximately 120 confirmed cases reported as of 2016. C. bantiana is a highly neurotropic and thermotolerant fungus found in soil worldwide. The mode of entry into the CNS remains unknown, but inhalation of fungal spores or subcutaneous trauma have been suggested. Entry of fungal spores can cause cerebral phaeohyphomycosis with the main clinical manifestation of a brain abscess. Symptoms are non-specific and can include headache, fever, hemiparesis, aphasia, visual disturbances, and confusion. C. bantiana cerebral phaeohyphomycosis occurs in both immunocompetent and immunocompromised individuals, with a slightly higher prevalence in immunocompetent males for unknown reasons. Diagnosis is often delayed due to its nonspecific presentation and prevalence in individuals without pre-existing immunological disease. Prognosis is poor, with mortality rates of approximately 70% despite aggressive treatment. Treatment is not standardized but may include several anti-fungal agents and surgical intervention. Case reports documenting the variability seen with cerebral phaeohyphomycosis by C. bantiana can provide valuable insight into this emerging disease. C. bantiana’s neurotropic propensity also warrants cognitive investigation of the disease; however, there are currently limited descriptions of cognitive findings in published case reports of C. bantiana CNS infections.Participants and Methods:Here, we describe a case of a 35-year-old immunocompetent, college educated male with a CNS C. bantiana infection, presumably following a fall while biking in Costa Rica. First symptoms included left sided facial palsy, headache, and hand weakness, prompting extensive diagnostic workup, with diagnosis of C. bantiana infection confirmed 8 months after symptom onset. Initial treatment included anti-fungal agents and steroids, but his course of infection was complicated by infectious vasculitis with posterior circulation infarcts and obstructive hydrocephalus requiring ventriculoperitoneal shunt placement two years following the fungal infection diagnosis. The most recent brain MRI revealed encephalomalacia in global periventricular areas, two small masses, likely representing small fungal phlegmons, and enhancing lesions in the upper cervical spinal canal.Results:The patient reported cognitive changes following the infarcts and shunt placement including difficulties with spatial navigation, following directions, and articulating thoughts. Memory concerns and lapses in judgment were also reported. Results from a neuropsychological evaluation revealed high average baseline intellectual abilities with decrements in visuospatial processing, processing speed, executive functioning, and aspects of memory stemming from his executive dysfunction. At the time, his cognitive profile suggested parietal and frontosubcortical systems disruption meeting criteria for mild cognitive impairment. Two years later, the patient reported continuing cognitive difficulties prompting a follow-up neuropsychological evaluation. Results were similar to his first evaluation, revealing deficits in aspects of visuospatial processing, decreased verbal and visual learning, bradyphrenia and processing speed deficits, and difficulties with visual planning and organization. Minimal anxiety and depression, but increased apathy and executive dysfunction were endorsed on self-report measures.Conclusions:This case report highlights neurological sequela resulting from CNS infection with C. bantiana, -with a course complicated by subsequent strokes, hydrocephalus, and cognitive impairment-, and contributes additional insight into the relatively limited existing reports of an extremely rare but emerging disease.

Molecular and Cellular Mechanisms Underlying Neurologic Manifestations of Mosquito-Borne Flavivirus Infections.

Flaviviruses are a family of enveloped viruses with a positive-sense RNA genome, transmitted by arthropod vectors. These viruses are known for their broad cellular tropism leading to infection of multiple body systems, which can include the central nervous system. Neurologic effects of flavivirus infection can arise during both acute and post-acute infectious periods; however, the molecular and cellular mechanisms underlying post-acute sequelae are not fully understood. Here, we review recent studies that have examined molecular and cellular mechanisms that may contribute to neurologic sequelae following infection with the West Nile virus, Japanese encephalitis virus, Zika virus, dengue virus, and St. Louis encephalitis virus. Neuronal death, either from direct infection or due to the resultant inflammatory response, is a common mechanism by which flavivirus infection can lead to neurologic impairment. Other types of cellular damage, such as oxidative stress and DNA damage, appear to be more specific to certain viruses. This article aims to highlight mechanisms of cellular damage that are common across several flavivirus members and mechanisms that are more unique to specific members. Our goal is to inspire further research to improve understanding of this area in the hope of identifying treatment options for flavivirus-associated neurologic changes.

Progressive Lower Extremity Paralysis Caused by Intrathecal MTX-Induced Myelopathy Mimicking Guillain-Barre Syndrome: A Case Report.

Methotrexate (MTX) is commonly used in intrathecal chemotherapy for patients with acute lymphocytic leukemia (ALL) to prevent central nervous system (CNS) involvement. However, the use of MTX-based chemotherapy can lead to rare yet severe complications, such as MTX-induced myelopathy. Here, we report the case of MTX-induced myelopathy initially misdiagnosed as Guillain-Barre syndrome, leading to a delay in diagnosis and treatment. We present a case of a 39-year-old male with a history of B-cell acute lymphoblastic leukemia (B-ALL) who experienced bilateral foot paresthesia and progressive lower extremity weakness after intrathecal methotrexate (MTX) treatment. Initially, the patient was suspected as having Guillain-Barre syndrome (GBS) due to similar clinical features and nerve conduction studies. The patient received intravenous immunoglobulin (IVIG) treatment, but his condition worsened. T2-weighted images of the thoracic spinal cord revealed high signal intensity in both lateral and posterior columns, typically associated with subacute combined degeneration. However, elevated vitamin B12 levels ruled out SCD in this case. Based on the aforementioned findings, intrathecal methotrexate-induced myelopathy was diagnosed. This case highlights the diagnostic challenge posed by the similarity in clinical presentation between MTX-induced myelopathy and GBS. Differentiating between these conditions is critical for appropriate management. Prompt recognition and treatment with folate metabolism compounds may mitigate neurological sequelae.

Global trends and regional differences in disease burden of stroke among children: a trend analysis based on the global burden of disease study 2019

BackgroundStroke is a major cause of acute neurological symptoms in children with significant long-term neurological sequelae. However, data of diseases burden on stroke among children was lack. We aimed to be dedicated to analyze and compare global trends as well as regional and sociodemographic differences in stroke prevalence, incidence, mortality and disability-adjusted life-years (DALYs) among children aged 0 ~ 14 years.MethodWe obtained data on annual number of incident strokes, prevalent strokes, deaths, and DALYs, age-standardized incidence rates (ASIRs), prevalence rates (ASPRs), mortality rates (ASMRs) and DALY rates (ASDRs) of stroke among individuals aged 14 years and younger during 1990–2019 from the 2019 Global Burden of Disease Study. To quantify the temporal trends, we calculated changes (%) in number, and used joinpoint regression analysis to identify the average annual percentage changes (AAPCs) of age standardized rates.ResultGlobally, the incident strokes and prevalent strokes increased by 18.51% and 31.97%, respectively, but DALYs due to stroke and deaths due to stroke decreased by 60.18% and 65.03%, respectively, from 1990 to 2019. During the same period, ASIR increased by 0.21% (95%CI: 0.17, 0.24) from 18.02 to 100,000 population in 1990 to 19.11 per 100,000 in 2019; ASPR increased by 0.66% (95%CI: 0.36, 0.96) from 68.88 to 100,000 population in 1990 to 81.35 per 100,000 in 2019; while ASMR (AAPC= -3.94; 95%CI: -4.07, -3.81) and ASDR (AAPC= -3.50; 95%CI: -3.64, -3.36) both decreased. In 2019, the highest age standardized incidence, prevalence, mortality, and DALY rates all occurred in low sociodemographic index (SDI) regions. The greatest increase of age standardized incidence rate (AAPC = 0.21; 95%CI: 0.18, 0.25) and prevalence rate (AAPC = 1.15; 95%CI: 0.34, 1.96) both were in high SDI regions. Eastern Sub-Saharan Africa had the highest ASIR and ASPR in 2019, and Oceania had the highest ASMR and ASDR in 2019 across 21 GBD regions. High-income North America had the largest increase in ASIR (AAPC = 0.63; 95%CI: 0.59, 0.66) and ASPR (AAPC = 1.58; 95%CI: 0.54, 2.63). Against the overall decreasing trend of ASMR, an increasing trend of ASMR was found in Zimbabwe (AAPC = 0.91; 95%CI: 0.44, 1.37) and Botswana (AAPC = 0.74; 95%CI: 0.02, 1.47).ConclusionThe overall increasing stroke incidence and prevalence indicated that prevention and management of stroke among younger population should be critical in the future. Despite stroke mortality with falling trend worldwide, specific countries or territories present worrying increase in stroke mortality. Without urgent implementation of effective primary prevention strategies, the stroke burden of children will probably continue to grow across the world, particularly in high-SDI countries.

Two Cases of Varicella Zoster Virus Meningitis without Fever and Rash: An Unexpected Clinical Presentation

Aseptic meningitis caused by Varicella-Zoster virus (VZV) is a rare phenomenon in the healthy population. Immunocompromised patients are predominantly affected by viral reactivation, characterized by rash and neurological symptoms, and meningitis as a rare complication. Herein, we report two cases of VZV meningitis in adult patients without rash and fever over a 4-month period. The first case was an immunocompetent 37-year-old male who presented with persistent headache, agitation and unclear speech. The second case was an immunocompromised 76-year-old male who was admitted to the emergency department with confusion, disorientation, dizziness, loss of consciousness, pain in the lower left extremities and difficulty in walking. Cerebrospinal fluid (CSF) analysis in both patients revealed a high leukocyte cell count with 97% lymphocytes. CSF gram staining and culture were negative. CSF polymerase chain reaction (PCR) analysis indicated VZV infection. Both patients were administered acyclovir for 14 days and were discharged without any neurological sequela. This case report series highlight the presentation of VZV as aseptic meningitis in both immunocompetent and immunocompromised patients without the typical clinical symptoms and should always be considered by the clinicians.

Assessing the association between on-field heading technique and head impact kinematics in a cohort of female youth soccer players

ABSTRACT There is concern that exposure to soccer headers may be associated with neurological sequelae. Training proper heading technique represents a coachable intervention that may reduce head acceleration exposure. The objective was to assess relationships between heading technique and head kinematics in female youth soccer players. Fourteen players (mean age = 14.4 years) wore instrumented mouthpieces during practices and games. Headers were reviewed by three raters to assign a technique score. Mixed models and LASSO regression evaluated associations of technique with peak linear acceleration (PLA), rotational acceleration (PRA), rotational velocity (PRV), and head impact power ratio (HIP Ratio) while adjusting for session type and ball delivery. Two hundred eighty-nine headers (n = 212 standing, n = 77 jumping) were analyzed. Technique score (p = 0.043) and the technique score – session type interaction (p = 0.004) were associated with PRA of standing headers, whereby each 10-unit increase in technique score was associated with an 8.6% decrease in PRA during games but a 5.1% increase in PRA during practices. Technique was not significantly associated with any other kinematic metrics; however, peak kinematics tended to decrease as technique score increased. LASSO regression identified back extension and shoulder/hip alignment as important predictors of peak kinematics. Additional research on heading technique and head acceleration is recommended.

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention.

Congenital hyperinsulinism and surgical outcome in a single tertiary center in Brazil

ObjectiveCongenital hyperinsulinism (CHI) is a heterogeneous genetic disease characterized by increased insulin secretion and causes persistent hypoglycemia in neonates and infants due to dysregulation of insulin secretion by pancreatic β cells. Babies with severe hypoglycemia and for whom medical treatment has been ineffective usually require surgical treatment with near-total pancreatectomy. To evaluate the clinical and surgical aspects affecting survival outcomes in babies diagnosed with CHI in a single tertiary care center. MethodsRetrospective Cohort study involving a single university tertiary center for the treatment of CHI. The authors study the demographics, clinical, laboratory, and surgical outcomes of this casuistic. Results61 % were female, 39 % male, Birth weight: 3576 g (±313); Age of onset of symptoms: from the 2nd hour of life to 28 days; Time between diagnosis and surgery ranged between 10 and 60 days; Medical clinical treatment, all patients received glucose solution with a continuous glucose infusion and diazoxide. 81 % of the patients used corticosteroids, 77 %. thiazide, 72 % octreotide, 27 % nifedipine; Neurological sequelae during development and growth: 54 % had some degree of delay in neuropsychomotor development, 27 % obesity. Surgery was performed open in 6 and 12 minimally invasive surgery (MIS). Histopathology: 2 focal and 16 diffuse, Length of stay (days) was lower in MIS (p < 0.05). Survival was 100 %. ConclusionsCHI is a rare and difficult-to-manage tumor that must be performed in a multidisciplinary and tertiary center. Most surgical results are good and the laparoscopic approach to disease has been the best choice for patients.

Cerebrospinal fluid metabolomic and proteomic characterization of neurologic post-acute sequelae of SARS-CoV-2 infection

The mechanism by which SARS-CoV-2 causes neurological post-acute sequelae of SARS-CoV-2 (neuro-PASC) remains unclear. Herein, we conducted proteomic and metabolomic analyses of cerebrospinal fluid (CSF) samples from 21 neuro-PASC patients, 45 healthy volunteers, and 26 inflammatory neurological diseases patients. Our data showed 69 differentially expressed metabolites and six differentially expressed proteins between neuro-PASC patients and healthy individuals. Elevated sphinganine and ST1A1, sphingolipid metabolism disorder, and attenuated inflammatory responses may contribute to the occurrence of neuro-PASC, whereas decreased levels of 7,8-dihydropterin and activation of steroid hormone biosynthesis may play a role in the repair process. Additionally, a biomarker cohort consisting of sphinganine, 7,8-dihydroneopterin, and ST1A1 was preliminarily demonstrated to have high value in diagnosing neuro-PASC. In summary, our study represents the first attempt to integrate the diagnostic benefits of CSF with the methodological advantages of multi-omics, thereby offering valuable insights into the pathogenesis of neuro-PASC and facilitating the work of neuroscientists in disclosing different neurological dimensions associated with COVID-19.

A suitable model to investigate acute neurological consequences of coronavirus infection.

The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis. Increased viral titers andmild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3. In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.

Perspective: Postoperative spinal epidural hematomas (pSEH) should be treated, not ignored.

Patients with postoperative spinal epidural hematomas (pSEH) typically require emergency treatment to avoid paralysis; these hematomas should not be ignored. pSEH patients need to undergo immediate MR studies to document the location/extent of their hematomas, and emergent surgical decompression with/ without fusion if warranted. The frequencies of symptomatic pSEH ranged in various series from 0.1%-4.46%. Major predisposing factors included; perioperative/postoperative coagulation abnormalities/disorders, multilevel spine surgeries, previous spine surgery, and intraoperative cerebrospinal fluid (CSF) leaks. For surgery at all spinal levels, one study observed pSEH developed within an average of 2.7 postoperative hours. Another series found 100% of cervical/thoracic, and 50% of lumbar pSEH were symptomatic within 24 postoperative hrs., while a third series noted a 24-48 postoperative window for pSEH to develop. Early recognition of postoperative symptoms/signs of pSEH, warrant immediate MR examinations to diagnose the local/extent of hemorrhages. Subsequent emergent spinal decompressions/fusions are critical to limit/avert permanent postoperative neurological deficits. Additionally, patients undergoing open or minimally invasive spinal procedures where pSEH are suspected, warrant immediate postoperative MR studies. Patients undergoing spinal surgery at any level typically become symptomatic from pSEH within 2.7 to 24 postoperative hours. Early recognition of new neurological deficits, immediate MR studies, and emergent surgery (i.e., if indicated) should limit/minimize postoperative neurological sequelae. Thus, pSEH should be treated, not ignored.

A 20-Year Study of Intracranial Pyogenic Complications of Sinusitis in Children.

Intracranial pyogenic complications of sinusitis in children can lead to serious sequelae. We characterize the clinical, epidemiologic and microbiologic characteristics of children with such complications over a 20-year period. Single-center retrospective chart review. Cases were identified based on International Classification of Diseases diagnostic codes (ICD)-9 and ICD-10 depending on the year and by reviewing all intracranial microbiologic samples. A total of 104 cases of complicated sinusitis were included after review of 1591 charts. Median age was 12 (IQR 9-14); 72 were male (69%). The most frequent complications were epidural empyema (n = 50, 48%), subdural empyema (n = 46, 44%) and Pott's puffy tumor (n = 27, 26%). 52% (n = 54) underwent neurosurgery and 46% (n = 48) underwent otolaryngologic surgery. The predominant pathogen isolated from sterile site specimens was Streptococcus anginosus (n = 40, 63%), but polymicrobial growth was common (n = 24; 38%). The median duration of intravenous antibiotic therapy was 51 days (IQR 42-80). Persistent neurologic sequelae (or death, n = 1) were found in 24% (n = 25) and were associated with the presence of cerebritis and extensive disease on neuroimaging ( P = 0.02 and P = 0.04, respectively). Intracranial complications of sinusitis continue to cause significant morbidity in children. Polymicrobial infections are common, which reinforces the need for broad-spectrum empiric antibiotic therapy and cautious adjustment of the antibiotic regimen based primarily on sterile site cultures. The association of neurologic sequelae with the presence of cerebritis and extensive intracranial involvement on neuroimaging suggest that delayed diagnosis may be a contributor to adverse outcome.

Microglial Activation: Key Players in Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction, which results in severe cognitive and neurological sequelae and an increased mortality rate in patients with sepsis. Depending on the stimulus, microglia (resident macrophages in the brain that are involved in SAE pathology and physiology) can adopt two polarization states (M1/M2), corresponding to altered microglial morphology, gene expression, and function. We systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE and demonstrated that microglia are closely related to SAE occurrence and development, and concomitant cognitive impairment. Finally, some potential therapeutic approaches that can prime microglia and neuroinflammation toward the beneficial restorative microglial phenotype in SAE were outlined.

Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication.

Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses are associated with persistent neuroinflammation and spontaneous recurrent seizures (SRS), also known as acquired epilepsy. Blood-brain barrier (BBB) impairment has recently been proposed as a pathogenic mechanism linking acute OP intoxication to chronic adverse neurologic outcomes. In this review, we briefly describe the cellular and molecular components of the BBB, review evidence of altered BBB integrity following acute OP intoxication, and discuss potential mechanisms by which acute OP intoxication may promote BBB dysfunction. We highlight the complex interplay between neuroinflammation and BBB dysfunction that suggests a positive feedforward interaction. Lastly, we examine research from diverse models and disease states that suggest mechanisms by which loss of BBB integrity may contribute to epileptogenic processes. Collectively, the literature identifies BBB impairment as a convergent mechanism of neurologic disease and justifies further mechanistic research into how acute OP intoxication causes BBB impairment and its role in the pathogenesis of SRS and potentially other long-term neurologic sequelae. Such research is critical for evaluating BBB stabilization as a neuroprotective strategy for mitigating OP-induced epilepsy and possibly seizure disorders of other etiologies. SIGNIFICANCE STATEMENT: Clinical and preclinical studies support a link between blood-brain barrier (BBB) dysfunction and epileptogenesis; however, a causal relationship has been difficult to prove. Mechanistic studies to delineate relationships between BBB dysfunction and epilepsy may provide novel insights into BBB stabilization as a neuroprotective strategy for mitigating epilepsy resulting from acute organophosphate (OP) intoxication and non-OP causes and potentially other adverse neurological conditions associated with acute OP intoxication, such as cognitive impairment.

Safety of laparoscopic liver resection for high-risk patients.

To investigate the safety of laparoscopic liver resections (LLRs) for high-risk patients (HRs) with preoperative comorbidities affecting the heart, lungs, kidneys, glucose tolerance, and central nervous system. This retrospective study included 585 patients who had undergone total hepatectomies from 2006 to 2020. Among them, 239 patients underwent LLRs, and 349 underwent open liver resections (OLRs). The safety and validity of LLRs were analyzed by comparing outcomes and preoperative records between HRs and nonhigh-risk patients (nHRs). HRs were defined as patients with any type of chronic heart disease rated New York Heart Association II or higher, chronic obstructive pulmonary disease rated stage III or higher, chronic kidney disease rated stage III or higher, insulin-dependent diabetes mellitus, or cerebrovascular disease with neurological sequelae. A total of 117 LLRs (49.0%) were performed in HRs, and there were more patients with ASA class III or higher than nHRs. Complications of Clavien-Dindo classification grade 3b or higher were not observed in HRs and in only one nHR. Furthermore, no postoperative exacerbations of the five HRs factors were observed in either group. Rigorous assessment of surgical indications and perioperative management can promote safe LLRs, even in HRs with comorbidities.

Hypercarbia and high-flow nasal oxygen use during anaesthesia - risking a failure to thrive?

Prevention of arterial oxygen desaturation during anaesthesia with high-flow nasal oxygen (HFNO) has gained greater acceptance for a widening range of procedures. However, during HFNO use there remains the potential for development of significant anaesthesia-associated apnoea or hypoventilation and the possibility of hypercarbia, with harmful cardiovascular or neurological sequelae. The aim of this study was to determine whether any HFNO-related hypercarbia adverse incidents had been reported on webAIRS, an online database of adverse anaesthesia-related incidents. Two relevant reports were identified of complications due to marked hypercarbia during HFNO use to maintain oxygenation. In both reports, HFNO and total intravenous anaesthesia were used during endoscopic procedures through the upper airway. In both, the extent of hypoventilation went undetected during HFNO use. An ensuing cardiac arrest was reported in one report, ascribed to acute hypercarbia-induced exacerbation of the patient's pre-existing pulmonary hypertension. In the other report, hypercarbia led to a prolonged duration of decreased level of consciousness post procedure, requiring ventilatory support. During the search, an additional 11 reports of postoperative hypercarbia-associated sedation were identified, unrelated to HFNO. In these additional reports an extended duration of severe acute hypercarbia led to sedation or loss of consciousness, consistent with the known effects of hypercarbia on consciousness. These 13 reports highlight the potential dangers of unrecognised and untreated hypercarbia, even if adequate oxygenation is maintained.