Long-term Neurological Deficits Research Articles

Pediatric neuroblastoma with intraspinal extension: the role of surgical management.

Neuroblastoma with spinal involvement accounts for up to 30% of pediatric spinal tumors and can cause profound neurological deficits. Chemotherapy is the preferred treatment option, but in select patients resection may be indicated. The goal of this study was to identify preoperative factors that led to early surgical intervention, with a specific emphasis on identifying differences on long-term neurological function and spinal deformity in the recent treatment era. A retrospective chart review was performed on all children diagnosed with neuroblastoma at a single institution from 2007 to 2020. Patient demographics, symptoms (motor deficit and sphincter dysfunction), and tumor characteristics (e.g., 123I metaiodobenzylguanidine [MIBG] avidity, MYCN amplification, chromosomal abnormality, pathology, catecholamine secretion, and stage) were recorded. Spine involvement included neural or vertebral extension, spinal cord compression, and/or T2 signal change on MRI. Survival, neurological status (motor deficit, sphincter dysfunction), and spine deformity at last follow-up were compared using univariate and multivariate analyses. The variables that contributed to neurological and deformity outcome were assessed with binomial logistic and linear regression models using R software. Seventy-seven of the 160 patients with neuroblastoma had spinal neuroblastoma, meaning either bone metastases alone (n = 43) or intraspinal extension with or without neurological deficit (n= 34). Most patients with spinal neuroblastoma were treated with chemotherapy and/or radiation therapy (97% and 57%, respectively). Resection of the spinal tumor was performed in 14 (18%) patients, all of whom also received chemotherapy. Between the surgical and nonsurgical patients, no baseline demographic differences were found. However, surgical patients were more likely to present with either motor deficits (50% vs 5%, p = 0.0011) or bladder/bowel dysfunction (14% vs 0%, p 0.035), and a shorter median time to onset of neurological symptoms (33 vs 80 days, p = 0.0096). Surgical patients also had a significantly shorter median overall survival (33.0 vs 54 months, p = 0.014). Of the 14 patients who underwent spine surgery, 2 patients underwent surgery at the time of diagnosis while the remaining 12 underwent initial chemotherapy followed later by resection. The 2 patients who underwent initial surgery had excellent outcomes, with neither long-term motor or bowel/bladder deficits nor spinal deformity. Surgical patients had shorter overall survival. However, the 2 patients with radiographic evidence of cord compression and acute neurological symptom onset who underwent initial, immediate surgery within 3 days of diagnosis had fewer long-term neurological deficits than surgical patients who underwent initial trials of chemotherapy. Thus, acute decompression may provide benefit in carefully selected patients with acute neurological deficits and cord compression on imaging.

Surgical corridor formation by minimally invasive lateral occipital infracortical supra-/transtentorial (OICST) approach in pineal region tumor surgery: A review of 11 cases

IntroductionThe pineal region is a hard-to-reach part of the brain. There is no unequivocal opinion on the choice of a surgical approach to the pineal region. The surgical approaches described differ in both trajectory (infra- and supratentorial, interhemispheric) and size of craniotomy. They have advantages and disadvantages. The minimally invasive lateral occipital infracortical supra-/transtentorial (OICST) approach we have described has all the advantages of the standard supratentorial approach and minimizes its disadvantages, namely, compression and contusion of the occipital lobe. The minimally invasive craniotomy and small surgical corridor facilitate that. MethodsWe describe 11 consecutive patients with various pineal region tumors (7 cases of pineal cysts, 2 cases of pinealocytoma, 1 case of medulloblastoma, and 1 case of meningioma) who were operated on in our hospital using the lateral OICST approach. Preoperative planning was performed using Surgical Theater®. The surgical corridor was formed using a retractor made from half of a syringe shortened according to the length of the surgical corridor. Preoperative lumbar drain was used. ResultsThe pineal region tumors were completely resected in all cases. The mean craniotomy size was 2.22 × 1.79 cm. No long-term neurological deficits were reported. ConclusionsThe use of semicircular retractors and intraoperative CSF drainage via a lumbar drain allows to form a small surgical corridor to the pineal region via minimally invasive craniotomy. This reduces traction and traumatization of the occipital lobe, as well as minimizes intra- and postoperative risks.

Probing Multiple Transplant Delivery Routes of CD+34 Stem Cells for Promoting Behavioral and Histological Benefits in Experimental Ischemic Stroke.

Stroke is a leading cause of death in the US and around the world but with limited treatment options. Survivors often present with long-term cognitive and neurological deficits. Stem cell-based therapy has emerged as a potential treatment for stroke. While stem cell transplantation in stroke has reached clinical trials, mostly safety outcomes have been reported with efficacy readouts warranting more studies. In an effort to optimize the stem cell regimen for stroke, here we conducted vis-a-vis comparison of different routes of transplantation, namely, intracerebral, intraarterial, and intranasal delivery of expanded human CD34 + stem cells, called ProtheraCytes, in the established stroke model of transient middle cerebral artery occlusion (MCAO) using adult Sprague-Dawley rats. After adjusting for the dose and subacute timing of cell delivery, animals were randomly assigned to receive either ProtheraCytes or vehicle. Motor and neurological assays from days 7 to 28 post-stroke revealed significant functional recovery across all 3 delivery routes of ProtheraCytes compared to vehicle-treated stroke rats. Additionally, ProtheraCytes-transplanted stroke rats displayed significantly reduced infarct size and cell loss in the peri-infarct area coupled with enhanced neurogenesis and angiogenesis compared to vehicle-treated stroke rats. These results highlight the safety and efficacy of transplanting ProtheraCytes, including via the minimally invasive intranasal route, in conferring robust and stable behavioral and histological positive outcomes in experimental stroke.

Establishment of a rat model of severe spontaneous intracerebral hemorrhage

BackgroundSevere intracerebral hemorrhage (ICH) is the most devastating subtype of stroke resulting in high mortality and disability. At present, the development of targeted treatments to minimize the high morbidity and mortality is limited partly due to the lack of a severe ICH animal model. In this study, we aimed to establish an accurate severe ICH model in rats and examine the pathological and physiological changes associated with ICH. MethodsA rat model of severe ICH model was established by intrastriatal injection of autologous blood using different blood volumes (ICH 100 µL group, ICH 130 µL group, ICH 160 µL group, ICH 170 µL group, and ICH 180 µL group). The mortality was assessed during the 28-day post-ICH period. Short- and long-term neurological deficits were evaluated using the Longa method, foot fault, falling latency, and Morris water maze tests. Brain water content, hematoma volume, hemoglobin content, and magnetic resonance imaging were assessed to determine the extent of brain injury. Immunofluorescence staining was conducted to examine microglial activation and neuronal apoptosis. Hematoxylin and eosin (H&E) staining, lung water content, and western blotting were used to assess lung injury following ICH. ResultsThe mortality of ICH rats increased significantly with an increase in autologous blood injection. The 28-day mortality in the 100 µL, 130 µL, 160 µL, 170 µL, and 180 µL ICH groups were 5%, 20%, 40%, 75%, and 100%, respectively. A significantly higher 28-day mortality was observed in the ICH 160 µL group compared to the ICH 100 µL group. The ICH 160 µL group exhibited significantly increased neurological deficits, brain edema, hematoma volume, and hemoglobin content compared to the sham group. Compared with the sham operation group, the activation of microglia and neuronal death in ICH 160 µL rats increased. The use of H&E staining and western blotting demonstrated that disruption of the intra-alveolar structure, alveolar edema, and infiltration of inflammatory cells and cytokines into the lung tissue were more severe in the ICH 160 µL group than the sham group. ConclusionsA severe ICH model in rats was successfully established using an injection of autologous blood at a volume of 160 µL. This model may provide a valuable tool to examine the pathological mechanisms and potential therapeutic interventions of severe ICH.

Painless nondiabetic lumbosacral radiculoplexus neuropathy with complete recovery: a case report

BackgroundLumbosacral radiculoplexus neuropathy, also known as amyotrophy, is an uncommon monophasic disorder characterized by inflammation of the lumbosacral nerve roots and plexuses. Lumbosacral radiculoplexus neuropathy is usually associated with diabetes mellitus, is typically painful at presentation, and often associated with long-term residual neurologic deficits. We report a case of painless, nondiabetic lumbosacral radiculoplexus neuropathy in a young Chinese woman, who made a full recovery after treatment with intravenous immunoglobulin, adding an atypical case to the scarce literature on lumbosacral radiculoplexus neuropathy.Case presentationA 35-year-old Chinese woman presented to our emergency department with 1-week history of painless left lower limb weakness and numbness. Examination revealed weakness confined to the left lower limb but spanning various nerves and myotomes, with abnormal sensation. Clinical localization to the lumbosacral plexus was supported by neurodiagnostic tests, and magnetic resonance imaging of the lumbosacral plexus showed that the nerve roots were also involved. After treatment with intravenous immunoglobulin for nondiabetic lumbosacral radiculoplexus neuropathy, the patient had a full recovery.ConclusionOur patient’s case highlights that lumbosacral radiculoplexus neuropathy, an already rare disorder, can occur in the absence of diabetes mellitus and pain, making it even harder to recognize. A systematic and meticulous clinical approach, supported by intelligent selection of adjunctive tests, is required for localization and diagnosis. With an accurate diagnosis, our case also demonstrates that appropriate and prompt treatment can lead to complete recovery, despite previous reports suggesting a high prevalence of long-term residual deficits after lumbosacral radiculoplexus neuropathy.

Symposium 01: Neuropsychological Outcomes Following Pediatric Stroke: Research Trends and Advances

Summary Abstract:Stroke is an important cause of acquired brain injury in youth and a significant source of childhood disability. Up to 80% of survivors suffer long-term neurological deficits, including impairments across a range of neuropsychological domains. An improved understanding of neuropsychological outcomes is key to optimizing clinical care, improving evaluation of prognosis, and developing effective rehabilitation and intervention strategies. The proposed symposium will begin with a literature review on neuropsychological outcomes following pediatric stroke. Next, four studies will be presented, each posing distinct and complementary research questions regarding predictors of outcomes. The roles of both clinical (e.g., lesion size, motor impairment, inflammatory response) and environmental factors (e.g., socioeconomic status, family functioning) will be explored regarding cognitive, social-emotional, and behavioral outcomes. The symposium will end with a Q&A period.Attendees will leave with an in-depth understanding of recent trends and scientific advances in research on neuropsychological outcomes in pediatric stroke, which should inform clinical practice and research directions. The first presentation examines predictors of neuropsychological outcomes following pediatric stroke. Findings have often conflicted, and more research is needed to disentangle the effects of predictors on specific domains. Explored predictors include: age at stroke; stroke subtype (hemorrhagic vs. ischemic); lesion location; lesion size; time since stroke; neurologic severity; seizure disorder; and socioeconomic status. This study examines the impact of these predictors on distinct neuropsychological domains. The next presentation addresses associations between neuropsychological outcomes and motor functioning following pediatric stroke. The development of cognitive and motor skills is interrelated and they share common neural substrates. In other populations, motor functioning predicts intellectual ability, and brain connectivity underlies this association. This study investigates associations between motor functioning and global neuropsychological outcomes in children with stroke and explores clinical features associated with motor impairments. The third presentation explores mental health outcomes. Neuropsychological deficits can hinder academic advancement and social-emotional development and may place youth at increased risk for psychological concerns. An increased focus on mental health is warranted given that psychosocial and behavioral issues are often the most concerning problems for parents and teachers. This study uses a qualitative paradigm to shed light on lived experience of youth with stroke with a focus on mental health, relationships, and social competence. The fourth presentation consists of a systematic review exploring the association between inflammatory response and neuropsychological outcome. Stroke induces an inflammation in the central and peripheral nervous systems, and high levels of inflammatory markers following stroke have been associated with poorer cognitive outcomes. This study reviews the state of research on this topic with a focus on pro-inflammatory cytokines and c-reactive protein. The symposium topics covered lie at the heart of the INS mission to study brain-behavior relationships using a multidisciplinary lens, with an emphasis on sharing and applying scientific knowledge. The symposium seeks to inform professionals working with youth with stroke about cutting-edge research, clinically applicable and novel insights, and ideas for future research directions. In this way, our symposium contributes to evidence-based care and the advancement of research.

Cardiotocography, Hypoxia, and Feto-Neonatal Neurological Damage

Complications occurring at any level of fetal oxygen supply can result in hypoxemia, which may ultimately lead to hypoxia/acidosis and neurological damage. Hypoxic-ischemic encephalopathy (HIE) is the short-term neurological dysfunction caused by intrapartum hypoxia/acidosis. This diagnosis requires the presence of several findings, including confirmation of newborn metabolic acidosis, low Apgar scores, early imaging evidence of cerebral edema, and the appearance of clinical signs of neurological dysfunction in the first 48 hours of life. Cerebral palsy (CP) comprises a heterogeneous group of nonprogressive movement and posture disorders, often accompanied by cognitive and sensory impairments, epilepsy, nutritional deficiencies, and secondary musculoskeletal lesions. Although CP is the most common long-term neurological complication associated with intrapartum hypoxia/acidosis, over 80% of cases are caused by other factors. Data on minor long-term neurological deficits are limited, but they suggest that less severe intellectual and motor impairments may result from intrapartum hypoxia/acidosis. Birth asphyxia is a broad term referring to intrapartum asphyxia severe enough to cause neurological damage in some newborns and, rarely, intrapartum or neonatal death. Cerebral palsy and long-term neurological complications such as learning difficulties and motor impairments may have causes other than birth asphyxia. Several intrapartum events can lead to asphyxia (i.e., hypoxia and metabolic acidosis), increasing the likelihood of neurological injury. The cardiotocograph (CTG) is a screening tool used to assess fetal well-being during labor and to identify the possibility of asphyxia. An abnormal CTG, sometimes severe enough to be described as a pathological trace, is commonly referred to as “fetal distress”, although many fetuses with such traces may not have hypoxia and metabolic acidosis. In current practice, these events are appropriately termed “pathological CTG trace” or “acidotic pH” rather than “fetal distress”. Accurate interpretation of the CTG is essential, and it is important to recognize a fetus displaying a pathological CTG in labor, which may imply possible hypoxia and birth asphyxia. Considering the broader clinical context when interpreting the CTG and taking timely and appropriate action based on the findings may help prevent birth asphyxia.

Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke

Ischemic white matter injury leads to long-term neurological deficits and lacks effective medication. Growth arrest specific protein 6 (Gas6) clears myelin debris, which is hypothesized to promote white matter integrity in experimental stroke models. By the middle cerebral artery occlusion (MCAO) stroke model, we observed that Gas6 reduced infarcted volume and behavior deficits 4 weeks after MCAO. Compared with control mice, Gas6-treatment mice represented higher FA values in the ipsilateral external capsules by MRI DTI scan. The SMI32/MBP ratio of the ipsilateral cortex and striatum was profoundly alleviated by Gas6 administration. Gas6-treatment group manifested thicker myelin sheaths than the control group by electron microscopy. We observed that Gas6 mainly promoted OPC maturation, which was closely related to microglia. Mechanically, Gas6 accelerated microglia-mediated myelin debris clearance and cholesterol transport protein expression (abca1, abcg1, apoc1, apoe) in vivo and in vitro, accordingly less myelin debris and lipid deposited in Gas6 treated stroke mice. HX531 (RXR inhibitor) administration mitigated the functions of Gas6 in speeding up debris clearance and cholesterol transport protein expression. Generally, we concluded that Gas6 cleared myelin debris and promoted cholesterol transportation protein expression through activating RXR, which could be one critical mechanism contributing to white matter repair after stroke.

Posterior fossa tumor resection in children: a case report and the role of intraoperative neurophysiologic monitoring

Introduction/Background: Surgery plays a crucial role in the surgical management of posterior fossa tumors in children, but maximizing the resection while preserving function remains challenging. Along with other tools available to the surgeon, intraoperative neuromonitoring aims at improving safety during these complex interventions. This case report highlights the role of real-time intraoperative neuromonitoring during surgery and its impact on the surgeon's decision-making process. Case report: We present the case of a 10-year-old boy with a fourth ventricle medulloblastoma, who underwent microneurosurgical resection under intraoperative neuromonitoring. The use of neurophysiological monitoring yielded relevant information during the tumor dissection of the floor of the fourth ventricle, the most crucial step of surgery, thus helping the surgeon to change tactics to minimize long-term neurological deficits. Conclusion: In combination with meticulous microneurosurgery techniques, modern anesthetic regimens, and ultrasonic aspiration, intraoperative neuromonitoring adds up to the surgeon's armamentarium for increasing safety and improving outcomes following surgery for pediatric patients bearing posterior fossa tumors.

Purinergic neurotransmission receptor P2X4 silencing alleviates intracerebral hemorrhage-induced neuroinflammation by blocking the NLRP1/Caspase-1 pathway

This study is performed to explore the role of P2X4 in intracerebral hemorrhage (ICH) and the association between P2X4 and the NLRP1/Caspase-1 pathway. The mouse ICH model was established via collagenase injection into the right basal ganglia. P2X4 expression in brain tissues was knocked down via intracerebroventricular injection with adeno-associated virus (AAV) harboring shRNA against shP2X4. The gene expression of P2X4 and protein levels related to NLRP1 inflammasome were detected using qRT-PCR and Western blot analysis, respectively. Muramyl dipeptide (an activator of NLRP1) was used to activate NLRP1 in brain tissues. ICH induced high expression of P2X4 in mouse brain tissues. The knockdown of P2X4 alleviated short- and long-term neurological deficits of ICH mice, as well as inhibited the tissue expression and serum levels of pro-inflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-1β. Additionally, the expressions of NLRP1, ASC, and pro-Caspase-1 were down-regulated upon P2X4 silencing. Moreover, neurological impairment and the expression and secretion of cytokines after P2X4 silencing were aggravated by the additional administration of MDP. P2X4 knockdown represses neuroinflammation in brain tissues after ICH. Mechanistically, P2X4 inhibition exerts a neuroprotective effect in ICH by blocking the NLRP1/Caspase-1 pathway.

Admission Clinical and EEG Features Associated With Mortality and Long-term Neurologic and Cognitive Outcomes in Pediatric Cerebral Malaria.

For children with cerebral malaria, mortality is high, and in survivors, long-term neurologic and cognitive dysfunctions are common. While specific clinical factors are associated with death or long-term neurocognitive morbidity in cerebral malaria, the association of EEG features with these outcomes, particularly neurocognitive outcomes, is less well characterized. In this prospective cohort study of 149 children age 6 months to 12 years who survived cerebral malaria in Kampala, Uganda, we evaluated whether depth of coma, number of clinical seizures, or EEG features during hospitalization were associated with mortality during hospitalization, short-term and long-term neurologic deficits, or long-term cognitive outcomes (overall cognition, attention, memory) over the 2-year follow-up. Higher Blantyre or Glasgow Coma Scores (BCS and GCS, respectively), higher background voltage, and presence of normal reactivity on EEG were each associated with lower mortality. Among clinical and EEG features, the presence of >4 seizures on admission had the best combination of negative and positive predictive values for neurologic deficits in follow-up. In multivariable modeling of cognitive outcomes, the number of seizures and specific EEG features showed independent association with better outcomes. In children younger than 5 years throughout the study, seizure number and presence of vertex sharp waves were independently associated with better posthospitalization cognitive performance, faster dominant frequency with better attention, and higher average background voltage and faster dominant background frequency with better associative memory. In children younger than 5 years at CM episode but 5 years or older at cognitive testing, seizure number, background dominant frequency, and the presence of vertex sharp waves were each associated with changes in cognition, seizure number and variability with attention, and seizure number with working memory. In children with cerebral malaria, seizure number is strongly associated with the risk of long-term neurologic deficits, while seizure number and specific EEG features (average background voltage, dominant rhythm frequency, presence of vertex sharp waves, presence of variability) are independently associated with cognitive outcomes. Future studies should evaluate the predictive value of these findings.

Perturbations in neural stem cell function during a neurotropic viral infection in juvenile mice.

Viral infections of the central nervous system (CNS) often cause worse neurological outcomes in younger hosts. Throughout childhood, the brain undergoes extensive development and refinement to produce functional neural networks. Network function is maintained partly with the help of neural stem cells (NSCs) that replace neuronal and glia subtypes in the two neurogenic niches of the brain (the hippocampus and subventricular zone). Accumulating evidence suggests that viruses disrupt NSC function in adulthood and infancy, but the in vivo impact of childhood infections on acute and long-term NSC function is unknown. Using a juvenile mouse model of measles virus (MeV) infection, where only mature neurons in the brain are infected, we defined the effects of the antiviral immune response on NSCs from juvenile to adult stages of life. We found that (a) virus persists in the brains of survivors despite an anti-viral immune response; (b) NSC numbers decrease dramatically during early infection, but ultimately stabilize in adult survivors; (c) infection is associated with mild apoptosis throughout the juvenile brain, but NSC proliferation is unchanged; (d) the loss of NSC numbers is dependent upon the stage of NSC differentiation; and (e) immature neurons increase early during infection, concurrent with depletion of NSC pools. Collectively, we show that NSCs are exquisitely sensitive to the inflammatory microenvironment created during neuron-restricted MeV infection in juveniles, responding with an early loss of NSCs but increased neurogenesis. These studies provide insight into potential cellular mechanisms associated with long-term neurological deficits in survivors of childhood CNS infections.

Impact of postnatal weight gain on brain white matter maturation in very preterm infants.

Very preterm infants (VPIs, <32 weeks gestational age at birth) are prone to long-term neurological deficits. While the effects of birth weight and postnatal growth on VPIs' neurological outcome are well established, the neurobiological mechanism behind these associations remains elusive. In this study, we utilized diffusion tensor imaging (DTI) to characterize how birth weight and postnatal weight gain influence VPIs' white matter (WM) maturation. We included VPIs with complete birth and postnatal weight data in their health record, and DTI scan as part of their predischarge Magnetic Resonance Imaging (MRI). We conducted voxel-wise general linear model and tract-based regression analyses to explore the impact of birth weight and postnatal weight gain on WM maturation. We included 91 VPIs in our analysis. After controlling for gestational age at birth and time between birth and scan, higher birth weight Z-scores were associated with DTI markers of more mature WM tracts, most prominently in the corpus callosum and sagittal striatum. The postnatal weight Z-score changes over the first 4 weeks of life were also associated with increased maturity in these WM tracts, when controlling for gestational age at birth, birth weight Z-score, and time between birth and scan. In VPIs, birth weight and post-natal weight gain are associated with markers of brain WM maturation, particularly in the corpus callosum, which can be captured on discharge MRI. These neuroimaging metrics can serve as potential biomarkers for the early effects of nutritional interventions on VPIs' brain development.

Tick-borne encephalitis: A comprehensive review of the epidemiology, virology, and clinical picture.

Tick-borne encephalitis virus (TBEV) is a flavivirus commonly found in at least 27 European and Asian countries. It is an emerging public health problem, with steadily increasing case numbers over recent decades. Tick-borne encephalitis virus affects between 10,000 and 15,000 patients annually. Infection occurs through the bite of an infected tick and, much less commonly, through infected milk consumption or aerosols. The TBEV genome comprises a positive-sense single-stranded RNA molecule of ∼11 kilobases. The open reading frame is>10,000 bases long, flanked by untranslated regions (UTR), and encodes a polyprotein that is co- and post-transcriptionally processed into three structural and seven non-structural proteins. Tick-borne encephalitis virus infection results in encephalitis, often with a characteristic biphasic disease course. After a short incubation time, the viraemic phase is characterised by non-specific influenza-like symptoms. After an asymptomatic period of 2-7days, more than half of patients show progression to a neurological phase, usually characterised by central and, rarely, peripheral nervous system symptoms. Mortality is low-around 1% of confirmed cases, depending on the viral subtype. After acute tick-borne encephalitis (TBE), a minority of patients experience long-term neurological deficits. Additionally, 40%-50% of patients develop a post-encephalitic syndrome, which significantly impairs daily activities and quality of life. Although TBEV has been described for several decades, no specific treatment exists. Much remains unknown regarding the objective assessment of long-lasting sequelae. Additional research is needed to better understand, prevent, and treat TBE. In this review, we aim to provide a comprehensive overview of the epidemiology, virology, and clinical picture of TBE.

NLRP3 inflammasome activation underlies the neuro-oxidative stress associated with Methamphetamine (METH) and SARS-CoV2 induced co-morbidity in human microglia

Abstract Acute and chronic use of Methamphetamine (METH) has critical immunological implications and METH users are more vulnerable to SARS-CoV2 infection. Inflammasomes are activated in response to SARS-CoV2 infection. METH also activates NLRP3 inflammasome in microglia and promotes neuro cognitive deficits. The goal of the study was to examine the involvement of NLRP3 inflammasome in METH and/or SARS-CoV2 induced neuro-oxidative stress in microglial cells. Our results suggests that METH +/− SARS-CoV2 initiated a neuro immune-inflammatory response and mitochondrial oxidative stress via NLRP3 inflammasome activation induced increased Caspase −1 and increased lipid peroxidation. Our data suggests that SARS-CoV2 infection in METH abusing subjects may result in long-term neurological deficits resulting from microglial dysfunction and apoptosis attributed to NLRP3 inflammasome activation.

Establishing a Standardized Clinical Consensus for Reporting Complications Following Lateral Lumbar Interbody Fusion.

Background and Objectives: Mitigating post-operative complications is a key metric of success following interbody fusion. LLIF is associated with a unique complication profile when compared to other approaches, and while numerous studies have attempted to report the incidence of post-operative complications, there is currently no consensus regarding their definitions or reporting structure. The aim of this study was to standardize the classification of complications specific to lateral lumbar interbody fusion (LLIF). Materials and Methods: A search algorithm was employed to identify all the articles that described complications following LLIF. A modified Delphi technique was then used to perform three rounds of consensus among twenty-six anonymized experts across seven countries. Published complications were classified as major, minor, or non-complications using a 60% agreement threshold for consensus. Results: A total of 23 articles were extracted, describing 52 individual complications associated with LLIF. In Round 1, forty-one of the fifty-two events were identified as a complication, while seven were considered to be approach-related occurrences. In Round 2, 36 of the 41 events with complication consensus were classified as major or minor. In Round 3, forty-nine of the fifty-two events were ultimately classified into major or minor complications with consensus, while three events remained without agreement. Vascular injuries, long-term neurologic deficits, and return to the operating room for various etiologies were identified as important consensus complications following LLIF. Non-union did not reach significance and was not classified as a complication. Conclusions: These data provide the first, systematic classification scheme of complications following LLIF. These findings may improve the consistency in the future reporting and analysis of surgical outcomes following LLIF.

Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2.

Extracellular signal-regulated kinase 1 and 2 (Erk1/2) signaling has been shown to be involved in brain injury after subarachnoid hemorrhage (SAH). A first-in-human phase I study reported that ravoxertinib hydrochloride (RAH), a novel Erk1/2 inhibitor, has an acceptable safety profile and pharmacodynamic effects. Here, we showed that the level of Erk1/2 phosphorylation (p-Erk1/2) was significantly increased in the cerebrospinal fluid (CSF) of aneurysmal subarachnoid hemorrhage (aSAH) patients who developed poor outcomes. In a rat SAH model that was produced by the intracranial endovascular perforation method, western blot observed that the level of p-Erk1/2 was also increased in the CSF and basal cortex, showing a similar trend with aSAH patients. Immunofluorescence and western blot indicated that RAH treatment (i.c.v injection, 30 min post-SAH) attenuates the SAH-induced increase of p-Erk1/2 at 24 h in rats. RAH treatment can improve experimental SAH-induced long-term sensorimotor and spatial learning deficits that are evaluated by the Morris water maze, rotarod test, foot-fault test, and forelimb placing test. Moreover, RAH treatment attenuates neurobehavioral deficits, the blood-brain barrier damage, and cerebral edema at 72 h after SAH in rats. Furthermore, RAH treatment decreases the SAH-elevated apoptosis-related factor active caspase-3 and the necroptosis-related factor RIPK1 expression at 72 h in rats. Immunofluorescence analysis showed that RAH attenuated neuronal apoptosis but not neuronal necroptosis in the basal cortex at 72 h after SAH in rats. Altogether, our results suggest that RAH improves long-term neurologic deficits through early inhibition of Erk1/2 in experimental SAH.

Management of Peri-mesencephalic Hemorrhage leading to acute hydrocephalus in an infant following Mild Trauma (P12-5.030)

<h3>Objective:</h3> To characterize etiology, risk factors, and management of peri-mesencephalic hemorrhage and severity of clinical presentation in pediatric populations <h3>Background:</h3> Peri-mesencephalic hemorrhage (PMH) is a form of mild subarachnoid hemorrhage (SAH) where the bleed is localized near the midbrain or just anterior to the pons without intraparenchymal or ventricular extension. It is typically a non-aneurysmal SAH (NASAH) with no clear source of bleeding after extensive vessel imaging including angiogram. Many hypotheses have been proposed such as spontaneous rupture of a perforating artery or an entirely venous source. Traumatic causes are rarely described. Outcomes are typically much better than aneurysmal SAH and other forms of NASAH with very low risk of rebleed, hydrocephalus, and little to no long-term neurologic deficits. <h3>Design/Methods:</h3> case study <h3>Results:</h3> An 8-month-old developmentally appropriate girl with no prior history of trauma who presented with three episodes of vomiting and lethargy 3–4 hours after a fall from standing position due to loss of balance while she was holding on to a folding chair. She fell backwards onto a tile floor and chair fell on top of her. CTH was obtained which showed prepontine and pontocerebellar hemorrhage spreading to ambient cisterns, IVH of the lateral and 3rd ventricles with acute noncommunicating hydrocephalus and no fracture. CTA with contrast and later MRI brain, MRA, and angiogram did not show any aneurysm or AVM per neurosurgery. EVD was placed with improvement in mental status. Repeat MRI brain was stable with very slight interval increase ventricle, and patient discharged home after 3rd ventriculostomy with no deficits. <h3>Conclusions:</h3> Though rare, trauma is a potential cause of PMH in pediatric populations and can present with acute hydrocephalus due to obstruction of ventricular system successfully treated with EVD placement and 3rd ventriculostomy with positive outcome. Hemorrhage may potentially be due to rupture of small perforating arteries through a sheering force. <b>Disclosure:</b> Dr. Johnson has nothing to disclose. Dr. Ming has nothing to disclose. Dr. Heshmati has nothing to disclose.

Chaperone-mediated autophagy (CMA) alleviates cognitive impairment by reducing neuronal death in sepsis-associated encephalopathy (SAE)

Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis, which causes long-term neurological deficits, such as cognitive impairment. Despite extensive research, there is still lack of specific treatments for SAE. Chaperone-mediated autophagy (CMA), a selective type of autophagy, has been reported to be related to cognitive dysfunctions in many neurodegenerative diseases. The aim of this study was to investigate the alteration of CMA activity in the hippocampus of SAE mice and explore the neuroprotective effect of enhanced CMA. Cecal ligation and puncture (CLP) was conducted to induce SAE. In the contextual fear conditioning test, the ratio of freezing time of CLP mice significantly decreased compared with that of the mice in the Sham group, indicating cognitive impairment in SAE mice. The expression of lysosome-associated membrane protein type 2A (Lamp2a) and chaperone heat shock cognate 71 kDa protein (Hsc70), positive markers for CMA activity, decreased in hippocampal neurons of SAE mice. Although overexpression of Lamp2a in neurons via adeno-associated virus injection in the hippocampus had little effect on the mortality of septic mice, this intervention significantly alleviated the memory impairments in contextual fear conditioning test, Y-maze test and novel objective recognition test, and attenuated the neural death observed in SAE mice. We further demonstrated that the overexpression of Lamp2a in the hippocampus increased the expression of phosphorylated cyclic-AMP response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), and suppressed the expression of cleaved caspase-3. Taken together, our study results suggested that the upregulation of CMA activity ameliorated cognitive impairments and neuron loss in SAE mice partially through the p-CREB-BDNF/Bcl-2 signaling pathways, providing a potential therapeutic target for SAE.

Electrical injuries and outcomes: A retrospective review

Electrical burns (EI) differ from other burn injuries in the immediate treatment given and delayed sequelae they manifest. This paper reviews our burn center’s experience with electrical injuries. All patients with electrical injuries admitted from January 2002 to August 2019 were included. Demographics; admission, injury, and treatment data; complications, including infection, graft loss, and neurologic injury; pertinent imaging, neurology consultation, neuropsychiatric testing; and mortality were collected. Subjects were divided into those who were exposed to high (>1000 volts), low (<1000 volts), and unknown voltage. The groups were compared. P < 0.05 was considered significant. One hundred sixty-two patients with electrical injuries were included. Fifty-five suffered low voltage, 55 high voltage, and 52 unknown voltage injuries. High voltage injuries were more likely to be male (98.2% vs. 83.6% low voltage vs. 94.2% unknown voltage, p = 0.015), to experience loss of consciousness (69.1% vs. 23.6% vs. 33.3%, p < 0.001), cardiac arrest (20% vs. 3.6% vs. 13.4%, p = 0.032), and undergo amputation (23.6% vs. 5.5% vs. 8.2%, p = 0.024). No significant differences were observed in long-term neurological deficits. Twenty-seven patients (16.7%) were found to have neurological deficits on or after admission; 48.2% recovered, 33.3% persisted, 7.4% died, and 11.1% did not follow-up with our burn center. Electrical injuries are associated with protean sequelae. Immediate complications include cardiac, renal, and deep burns. Neurologic complications, while uncommon, can occur immediately or are delayed.