Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity.

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Early Measures of TBI Severity Poorly Predict Later Individual Impairment in a Rat Fluid Percussion Model.

BACKGROUND: Multiple measures of injury severity are suggested as common data elements in preclinical traumatic brain injury (TBI) research. The robustness of these measures in characterizing injury severity is unclear. In particular, it is not known how reliably they predict individual outcomes after experimental TBI. METHODS: We assessed several commonly used measures of initial injury severity for their ability to predict chronic cognitive outcomes in a rat lateral fluid percussion (LFPI) model of TBI. At the time of injury, we assessed reflex righting time, neurologic severity scores, and 24 h weight loss. Sixty days after LFPI, we evaluated working memory using a spontaneous alternation T-maze task. RESULTS: We found that righting time and weight loss had no correlation to chronic T-maze performance, while neurologic severity score correlated weakly. DISCUSSION: Taken together, our results indicate that commonly used early measures of injury severity do not robustly predict longer-term outcomes. This finding parallels the uncertainty in predicting individual outcomes in TBI clinical populations.

Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children.

Importance: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge. Objective: To characterize neurological, psychological, and quality of life sequelae after MIS-C. Design, Setting, and Participants: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023. Exposure: Diagnosis of MIS-C. Main Outcomes and Measures: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences. Results: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls. Conclusions and Relevance: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.

Update on Central Nervous System Effects of HIV in Adolescents and Young Adults.

PURPOSE OF REVIEW: : Behaviorally acquired (non-perinatal) HIV infection during adolescence and young adulthood occurs in the midst of key brain developmental processes such as frontal lobe neuronal pruning and myelination of white matter, but we know little about the effects of new infection and therapy on the developing brain. RECENT FINDINGS: Adolescents and young adults account for a disproportionately high fraction of new HIV infections each year. Limited data exist regarding neurocognitive performance in this age group, but suggest impairment is at least as prevalent as in older adults, despite lower viremia, higher CD4 + T cell counts, and shorter durations of infection in adolescents/young adults. Neuroimaging and neuropathologic studies specific to this population are underway. The full impact of HIV on brain growth and development in youth with behaviorally acquired HIV has yet to be determined; it must be investigated further to develop future targeted treatment and mitigation strategies.

Neurologic complications of infective endocarditis in children.

OBJECTIVES: To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications. STUDY DESIGN: Retrospective cohort study of children aged 0-18 years hospitalised at a tertiary children's hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis. RESULTS: Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications. CONCLUSIONS: Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.

Race and the emergency department management of febrile seizures.

To determine if racial disparities exist in the management of febrile seizures in a large pediatric emergency department (ED), We performed a retrospective cross-sectional analysis of children 6 months to 6 years-old who presented to the ED with a febrile seizure over a 4-year period. Multivariate logistic regression models were built to examine the association between race and the primary outcome of neuroimaging, and secondary outcomes of hospital admission and abortive anticonvulsant prescription at ED discharge. There were 980 ED visits during the study period. Overall, 4.0% of children underwent neuroimaging and 11.1% were admitted. Of the 871 children discharged from the ED, 9.4% were prescribed an abortive anticonvulsant. There were no differences by race in neuroimaging or hospital admission. However, black children were less likely to be prescribed abortive anticonvulsants (adjusted odds ratio [aOR] 0.47; 95% confidence interval [CI]: 0.23-0.96) compared to non-black peers, when adjusting for demographic and clinical confounders. Stratification by insurance revealed that this disparity existed in Medicaid-insured patients (aOR 0.33, 95% CI: 0.14-0.78) but not in privately-insured patients. We found no racial disparities in neuroimaging or hospital admission among ED patients with febrile seizures. We did find racial disparities in our secondary outcome of abortive anticonvulsant prescription, driven primarily by individuals on Medicaid insurance. This pattern of findings may reflect the lack of standardized recommendations regarding anticonvulsant prescription, in contrast to the guidelines issued for other ED management decisions. Further investigation into the potential for treatment guidelines to reduce racial disparities is needed.

The Impact of C1 Anterior Arch Preservation on Spine Stability After Odontoidectomy: Systematic Review and Meta-Analysis.

BACKGROUND: Odontoidectomy for symptomatic irreducible ventral brainstem compression at the craniovertebral junction may result in spine instability requiring subsequent instrumentation. There is no consensus on the importance of C1 anterior arch preservation in prevention of iatrogenic instability. We conducted a systematic review of the impact of C1 anterior arch preservation on postodontoidectomy spine stability. METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients undergoing odontoidectomy. Random-effect model meta-analyses were performed to compare spine stability between C1 anterior arch preservation versus removal and posttreatment outcomes between transoral approaches (TOAs) versus endoscopic endonasal approaches (EEAs). RESULTS: We included 27 studies comprising 462 patients. The most common lesions were basilar invagination (73.3%) and degenerative arthritis (12.6%). Symptoms included myelopathy (72%) and neck pain (43.9%). Odontoidectomy was performed through TOA (56.1%) and EEA corridors (34.4%). The C1 anterior arch was preserved in 16.7% of cases. Postodontoidectomy stabilization was performed in 83.3% patients. Median follow-up was 27 months (range, 0.1-145). Rates of spine instability were significantly lower (P = 0.004) when the C1 anterior arch was preserved. Postoperative clinical improvement and pooled complications were reported in 78.8% and 12.6% of patients, respectively, with no significant differences between TOA and EEA (P = 0.892; P = 0.346). Patients undergoing EEA had significantly higher rates of intraoperative cerebrospinal fluid leaks (P = 0.002). CONCLUSIONS: Odontoidectomy is safe and effective for treating craniovertebral junction lesions. Preservation of the C1 anterior arch seems to improve maintenance of spine stability. TOA and EEA show comparable outcomes and complication rates.

C1 Lateral Mass Screw Placement Through Endonasal Corridor for Purpose of O-C1 Fusion: Morphometric Analysis in Cadaveric Specimens.

BACKGROUND: Odontoidectomy may pose some risks for O-C1 and/or C1-C2 instability, with previous authors reporting techniques for endonasal C1-C2 fusion. However, no technique for endonasal O-C1 fusion currently exists. We sought to describe the feasibility of endonasal anterior C1 (AC1) screw placement for endonasal O-C1 fusion. METHODS: Seven adult cadaveric heads were studied for endonasal placement of 14 C1 screws. Using thin-cut computed tomography (CT)-based "snapshot" neuronavigation assistance, 4 mm x 22 mm screws were placed in the C1 lateral mass using a 0° driver. Post-placement CT scans were obtained to determine site-of-entry measured from C1 anterior tubercle, screw angulation in axial and sagittal planes, and screw proximity to the central canal and foramen transversarium. RESULTS: Average site-of-entry was 16.57 mm lateral, 2.23 mm rostral, and 5.53 mm deep to the anterior-most portion of the C1 ring. Average axial angulation was 19.49° lateral to midline, measured at the C1 level. Average sagittal angulation was 13.22° inferior to the palatal line, measured from the hard palate to the opisthion. Bicortical purchase was achieved in 11 screws (78.6%). Partial breach of the foramen transversarium was observed in 2 screws (14.3%), violation of the O-C1 joint space in 1 (7.1%), and violation of the central canal in 0 (0%). Average minimum screw distances from the unviolated foramen transversaria and central canal were 1.97 mm and 4.04 mm. CONCLUSIONS: Navigation-assisted endonasal placement of AC1 screws is feasible. Additional studies should investigate the biomechanical stability of anterior C1 screw-plating systems, with anterior condylar screws as superior fixation point, compared to traditional posterior O-C1 fusion.

Postinjury Treatment to Mitigate the Effects of Aeromedical Evacuation After Traumatic Brain Injury in a Porcine Model.

INTRODUCTION: Early aeromedical evacuation after traumatic brain injury (TBI) has been associated with worse neurologic outcomes in murine studies and military populations. The goal of this study was to determine if commonly utilized medications, including allopurinol, propranolol, or tranexamic acid (TXA), could mitigate the secondary traumatic brain injury experienced during the hypobaric and hypoxic environment of aeromedical evacuation. METHODS: Porcine TBI was induced via controlled cortical injury. Twenty nonsurvival pigs were separated into four groups (n = 5 each): TBI+25 mL normal saline (NS), TBI+4 mg propranolol, TBI+100 mg allopurinol, and TBI+1g TXA. The pigs then underwent simulated AE to an altitude of 8000 ft for 4 h with an SpO2 of 82-85% and were sacrificed 4 h later. Hemodynamics, serum cytokines, and hippocampal p-tau accumulation were assessed. An additional survival cohort was partially completed with TBI/NS (n = 5), TBI/propranolol (n = 2) and TBI/allopurinol groups (n = 2) survived to postinjury day 7. RESULTS: There were no significant differences in hemodynamics, tissue oxygenation, cerebral blood flow, or physiologic markers between treatment groups and saline controls. Transient differences in IL-1b and IL-6 were noted but did not persist. Neurological Severity Score (NSS) was significantly lower in the TBI + allopurinol group on POD one compared to NS and propranolol groups. P-tau accumulation was decreased in the nonsurvival animals treated with allopurinol and TXA compared to the TBI/NS group. CONCLUSIONS: Allopurinol, propranolol, and TXA, following TBI, do not induce adverse changes in systemic or cerebral hemodynamics during or after a simulated postinjury flight. While transient changes were noted in systemic cytokines and p-tau accumulation, further investigation will be needed to determine any persistent neurological effects of injury, flight, and pharmacologic treatment.

Differentiating Bell's Palsy From Lyme-Related Facial Palsy.

BACKGROUND AND OBJECTIVES: To describe the etiology and clinical course of pediatric acute-onset unilateral peripheral facial palsy (FP), to define factors that distinguish Bell's palsy from Lyme-related FP (LRFP), and to determine if early corticosteroid use impacts facial strength recovery in Bell's palsy or LRFP. METHODS: Retrospective cohort study of children 1 to 18 years old who received clinical care within our pediatric clinical care network (Lyme-endemic region) between 2013 and 2018 for acute-onset unilateral peripheral FP. RESULTS: The study included 306 children; 82 (27%) had LRFP, 209 (68%) had Bell's palsy, and 15 (5%) had FP of different etiology. Most children with LRFP presented between June and November (93%), and compared with Bell's palsy, more often had a preceding systemic prodrome, including fever, malaise, headache, myalgias, and/or arthralgias (55% vs 6%, P < .001). Neuroimaging and lumbar puncture did not add diagnostic value in isolated FP. Of the 226 children with Bell's palsy or LRFP with documented follow-up, FP was resolved in all but 1. There was no association between ultimate parent/clinician assessment of recovery and early corticosteroid use. CONCLUSIONS: Bell's palsy and LRFP were common causes of pediatric FP in our Lyme endemic region. Systemic prodrome and calendar month may help distinguish LRFP from Bell's palsy at FP onset, guiding antibiotic use. Early corticosteroid use did not impact our measures of recovery, although subtle abnormalities may not have been appreciated, and time to recovery could not be assessed. Future prospective studies using standardized assessment tools at regular follow-up intervals are necessary.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

Remote and Persistent Alterations in Glutamate Receptor Subunit Composition Induced by Spreading Depolarizations in Rat Brain.

Spreading depolarizations (SDs) are massive breakdowns of ion homeostasis in the brain's gray matter and are a necessary pathologic mechanism for lesion development in various injury models. However, injury-induced SDs also propagate into remote, healthy tissue where they do not cause cell death, yet their functional long-term effects are unknown. Here we induced SDs in uninjured cortex and hippocampus of Sprague-Dawley rats to study their impact on glutamate receptor subunit expression after three days. We find that both cortical and hippocampal tissue exhibit changes in glutamate receptor subunit expression, including GluA1 and GluN2B, suggesting that SDs in healthy brain tissue may have a role in plasticity. This study is the first to show prolonged effects of SDs on glutamate signaling and has implications for neuroprotection strategies aimed at SD suppression.

KRSA: An R package and R Shiny web application for an end-to-end upstream kinase analysis of kinome array data.

Phosphorylation by serine-threonine and tyrosine kinases is critical for determining protein function. Array-based platforms for measuring reporter peptide signal levels allow for differential phosphorylation analysis between conditions for distinct active kinases. Peptide array technologies like the PamStation12 from PamGene allow for generating high-throughput, multi-dimensional, and complex functional proteomics data. As the adoption rate of such technologies increases, there is an imperative need for software tools that streamline the process of analyzing such data. We present Kinome Random Sampling Analyzer (KRSA), an R package and R Shiny web-application for analyzing kinome array data to help users better understand the patterns of functional proteomics in complex biological systems. KRSA is an All-In-One tool that reads, formats, fits models, analyzes, and visualizes PamStation12 kinome data. While the underlying algorithm has been experimentally validated in previous publications, we demonstrate KRSA workflow on dorsolateral prefrontal cortex (DLPFC) in male (n = 3) and female (n = 3) subjects to identify differential phosphorylation signatures and upstream kinase activity. Kinase activity differences between males and females were compared to a previously published kinome dataset (11 female and 7 male subjects) which showed similar global phosphorylation signals patterns.

Worldwide epidemiology of neuro-coronavirus disease in children: lessons for the next pandemic.

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions. RECENT FINDINGS: Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources. SUMMARY: Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.

Lack of Glutamate Receptor Subunit Expression Changes in Hippocampal Dentate Gyrus after Experimental Traumatic Brain Injury in a Rodent Model of Depression.

Traumatic brain injury (TBI) affects over 69 million people annually worldwide, and those with pre-existing depression have worse recovery. The molecular mechanisms that may contribute to poor recovery after TBI with co-morbid depression have not been established. TBI and depression have many commonalities including volume changes, myelin disruption, changes in proliferation, and changes in glutamatergic signaling. We used a well-established animal model of depression, the Wistar Kyoto (WKY) rat, to elucidate changes after TBI that may influence the recovery trajectory. We compared the histological and molecular outcomes in the hippocampal dentate gyrus after experimental TBI using the lateral fluid percussion injury (LFPI) in the WKY and the parent Wistar (WIS) strain. We showed that WKY had exaggerated myelin loss after LFPI and baseline deficits in proliferation. In addition, we showed that while after LFPI WIS rats exhibited glutamate receptor subunit changes, namely increased GluN2B, the WKY rats failed to show such injury-related changes. These differential responses to LFPI helped to elucidate the molecular characteristics that influence poor recovery after TBI in those with pre-existing depression and may lead to targets for future therapeutic interventions.

Influenza-Associated Neurologic Complications in Hospitalized Children.

OBJECTIVES: To define the incidence and characteristics of influenza-associated neurologic complications in a cohort of children hospitalized at a tertiary care pediatric hospital with laboratory-confirmed influenza and to identify associated clinical, epidemiologic, and virologic factors. STUDY DESIGN: This was an historical cohort study of children aged 0.5-18.0 years old hospitalized between 2010 and 2017 with laboratory-confirmed influenza. Children with immune compromise or a positive test due to recent receipt of live virus vaccine or recently resolved illness were excluded. Influenza-associated neurologic complications were defined as new-onset neurologic signs/symptoms during acute influenza illness without another clear etiology. RESULTS: At least 1 influenza-associated neurologic complication was identified in 10.8% (95% CI 9.1-12.6%, n = 131 of 1217) of hospitalizations with laboratory-confirmed influenza. Seizures (n = 97) and encephalopathy (n = 44) were the most commonly identified influenza-associated neurologic complications, although an additional 20 hospitalizations had other influenza-associated neurologic complications. Hospitalizations with influenza-associated neurologic complications were similar in age and influenza type (A/B) to those without. Children with a pre-existing neurologic diagnosis (n = 326) had a greater proportion of influenza-associated neurologic complications compared with those without (22.7% vs 6.4%, P < .001). Presence of a pre-existing neurologic diagnosis (aOR 4.6, P < .001), lack of seasonal influenza vaccination (aOR 1.6, P = .020), and age ≤5 years (aOR 1.6, P = .017) were independently associated with influenza-associated neurologic complications. CONCLUSIONS: Influenza-associated neurologic complications are common in children hospitalized with influenza, particularly those with pre-existing neurologic diagnoses. A better understanding of the epidemiology and factors associated with influenza-associated neurologic complications will direct future investigation into potential neuropathologic mechanisms and mitigating strategies. Vaccination is recommended and may help prevent influenza-associated neurologic complications in children.

Deficits in pattern separation and dentate gyrus proliferation after rodent lateral fluid percussion injury.

It has been demonstrated that adult born granule cells are generated after traumatic brain injury (TBI). There is evidence that these newly generated neurons are aberrant and are poised to contribute to poor cognitive function after TBI. Yet, there is also evidence that these newly generated neurons are important for cognitive recovery. Pattern separation is a cognitive task known to be dependent on the function of adult generated granule cells. Performance on this task and the relation to dentate gyrus dysfunction after TBI has not been previously studied. Here we subjected Sprague Dawley rats to lateral fluid percussion injury or sham and tested them on the dentate gyrus dependent task pattern separation. At 2 weeks after injury, we examined common markers of dentate gyrus function such as GSK3ß phosphorylation, Ki-67 immunohistochemistry, and generation of adult born granule cells. We found that injured animals have deficits in pattern separation. We additionally found a decrease in proliferative capacity at 2 weeks indicated by decreased phosphorylation of GSK3ß and Ki-67 immunopositivity as compared to sham animals. Lastly we found an increase in numbers of new neurons generated during the pattern separation task. These findings provide evidence that dentate gyrus dysfunction may be an important contributor to TBI pathology.

Intracranial Hypertension in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is characterized by fever and multiorgan system dysfunction. Neurologic complications of MIS-C are not well described. We present 4 patients with MIS-C who had intracranial hypertension and discuss the unique management considerations when this occurs concurrently with significant myocardial dysfunction.

Autonomic dysfunction following traumatic brain injury: translational insights.

Although there is a substantial amount of research on the neurological consequences of traumatic brain injury (TBI), there is a knowledge gap regarding the relationship between TBI and the pathophysiology of organ system dysfunction and autonomic dysregulation. In particular, the mechanisms or incidences of renal or cardiac complications after TBI are mostly unknown. Autonomic dysfunction following TBI exacerbates secondary injury and may contribute to nonneurologial complications that prolong hospital length of stay. Gaining insights into the mechanisms of autonomic dysfunction can guide advancements in monitoring and treatment paradigms to improve acute survival and long-term prognosis of TBI patients. In this paper, the authors will review the literature on autonomic dysfunction after TBI and possible mechanisms of paroxysmal sympathetic hyperactivity. Specifically, they will discuss the link among the brain, heart, and kidneys and review data to direct future research on and interventions for TBI-induced autonomic dysfunction.

Pioglitazone improves working memory performance when administered in chronic TBI.

Traumatic brain injury (TBI) is a leading cause of long-term disability in the United States. Even in comparatively mild injuries, cognitive and behavioral symptoms can persist for years, and there are currently no established strategies for mitigating symptoms in chronic injury. A key feature of TBI-induced damage in acute and chronic injury is disruption of metabolic pathways. As neurotransmission, and therefore cognition, are highly dependent on the supply of energy, we hypothesized that modulating metabolic activity could help restore behavioral performance even when treatment was initiated weeks after TBI. We treated rats with pioglitazone, a FDA-approved drug for diabetes, beginning 46 days after lateral fluid percussion injury and tested working memory performance in the radial arm maze (RAM) after 14 days of treatment. Pioglitazone treated TBI rats performed significantly better in the RAM test than untreated TBI rats, and similarly to control animals. While hexokinase activity in hippocampus was increased by pioglitazone treatment, there was no upregulation of either the neuronal glucose transporter or hexokinase enzyme expression. Expression of glial markers GFAP and Iba-1 were also not influenced by pioglitazone treatment. These studies suggest that targeting brain metabolism, in particular hippocampal metabolism, may be effective in alleviating cognitive symptoms in chronic TBI.