Persistent Neurological Deficits Research Articles

Vasospasm following brain tumor resection in children: institutional experience and systematic review.

Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors' knowledge, never been systematically reviewed. Therefore, the authors present what is to their knowledge the largest series of pediatric patients with this complication and systematically reviewed the literature for individual participant data. The authors conducted a retrospective review of 172 sellar and suprasellar tumors in pediatric patients who underwent surgery at the Montreal Children's Hospital between 1999 and 2017 to identify cases of vasospasm occurring after tumor resection. Descriptive statistics, including patient characteristics, intraoperative and postoperative findings, and outcome status, were collected. A systematic review was also conducted using three databases (PubMed, Web of Science, Embase) to identify reported cases available in the literature of vasospasm after tumor resection in children and collect individual participant data on these patients for further analysis. Six patients treated at Montreal Children's Hospital were identified, with an average age of 9.5 years (range 6-15 years). The prevalence of vasospasm after tumor resection was 3.5% (6/172). Vasospasm in all 6 patients occurred after craniotomy was performed to treat a suprasellar tumor. The average interval from surgery to symptoms was 3.25 days (range 12 hours-10 days). The most common tumor etiology was craniopharyngioma, seen in 4 cases. Extensive tumor encasement of blood vessels requiring significant operative manipulation was described in all 6 patients. A rapid decrease in serum sodium (exceeding 12 mEq/L/24 hrs or below 135 mEq/L) was seen in 4 patients. On final follow-up, 3 patients were left with significant disability, and all patients had persistent deficits. A systematic review of the literature revealed a total of 10 other patients whose characteristics and treatment were compared with those of the 6 patients treated at Montreal Children's Hospital. Vasospasm after tumor resection in children and youth is likely a rare entity, with a prevalence of 3.5% in this case series. Suprasellar tumor location (particularly craniopharyngioma tumor etiology), significant encasement of blood vessels by the tumor, and postoperative hyponatremia may be predictive factors. Outcome is poor, with most patients having significant persistent neurological deficits.

Management of Aneurysmal Subarachnoid Haemorrhage and its Complications: A Clinical Guide.

Aneurysmal subarachnoid hemorrhage (aSAH) is an emergency that needs prompt diagnosis and treatment with endovascular coiling or surgical clipping of the aneurysm to prevent re-bleeding. In addition to neurologic manifestations, aSAH can cause respiratory and cardiovascular complications. The prevention of hypoxemia and hypercarbia, control of intracranial pressure, and restoration of cerebral perfusion pressure should be the primary aims of early management. Secondarily, the most important causes of persistent neurological deficits and physical dependence in aSAH are vasospasm and delayed ischemia following bleeding. During that period, a focus on the detection, prevention, and treatment of vasospasm should be the rule. Transcranial Doppler allows detection and follow-up of vasospasm, especially in severe cases. Nimodipine is the only drug that has proven efficacy for treating vasospasm. Balloon angioplasty is performed in cases of resistance to medical treatment. Along with angioplasty, intra-arterial vasodilators can be administered. New diagnostic and therapeutic advances will hopefully improve outcomes in the near future.

Elevated brain derived neurotrophic factor in plasma and interleukin-6 levels in cerebrospinal fluid in meningitis compared to cerebral malaria

Neurological infections, such as Cerebral malaria (CM) and meningitis are associated with high mortality and in survivors, particularly young children, persistent neurologic deficits often remain. As brain inflammation plays a role in the development of these neurological sequelae, multiplex assays were used to assess a select set of immune mediators in both plasma and cerebrospinal fluid (CSF) from Zambian children with neurological infections.Both CM and meningitis patients showed high levels of markers for vascular inflammation, such as soluble ICAM-1 and angiopoietins. Although high levels of angiopoietin 1 and angiopoietin 2 were found in the meningitis group, their levels in the CSF were low and did not differ.As expected, there were high levels of cytokines and notably a significantly elevated IL-6 level in the CSF of the meningitis group. Interestingly, although elevated levels BDNF were found, BDNF levels were significantly higher in plasma of the meningitis group but similar in the CSF.The striking differences in plasma BDNF and IL-6 levels in the CSF point to markedly different neuro-pathological processes. Therefore, further investigations in the role of both IL-6 and BDNF in the neurological outcomes are needed.

A Young Female with SARS-CoV-2 Infection Presenting with Concurrent Neurological and Pulmonary Manifestations: A Case Report

Coronavirus disease 2019 (COVID-19), besides its well-known deleterious effects on the respiratory system, is also reported to affect the central nervous system (CNS), presenting with neurological manifestations, that are commoner among older patients with associated co-morbidities and in the critically ill with COVID pneumonia. Infective, cerebrovascular, and hypoxic-toxic-metabolic etiology have been implicated. Reported outcomes have been poor with persistent neurological deficits among the majority who have survived. We report a young lady who presented with neurological manifestations alongside moderately severe COVID-19 pneumonia. Diagnosed early and managed as severe encephalopathy after excluding infective and cerebrovascular aetiology. Responded well to conservative measures and made a complete recovery. Early recognition of neurological manifestations of COVID-19 disease followed by the institution of appropriate therapies improved the outcomes.

A Patient-centric Approach to Neuro-recovery after Acute Neurologic Injuries (P12-2.004)

<h3>Objective:</h3> To improve standardized documentation of outcomes in a post-ICU NeuroRecovery clinic and use these data to identify patient-centric goals for recovery. <h3>Background:</h3> Patients discharged after acute neurologic injuries require ongoing care for recovery and secondary neurologic complications. Most therapeutic trials for interventions geared to improve outcomes after acute neurologic injuries use measures of functionality as primary outcomes. Understanding patients’ perspectives can help providers tailor care and ultimately improve outcomes. <h3>Design/Methods:</h3> The Post-ICU NeuroRecovery clinic at a tertiary care hospital identified two outcome measures as part of a Quality Improvement (QI) initiative: 1) Modified Rankin Scale (mRS), and 2) Free-text response to “What is the single most important thing the NeuroRecovery clinic can do to support you/your loved one in the journey of recovery”. A QI intervention consisting of weekly reminders to providers to use a SmartPhrase that integrated the outcome measures into clinical documentation was implemented. <h3>Results:</h3> After the implementation of the QI intervention, documentation of the two outcomes improved from 33% to 63% for all clinic visits over a pilot period of 3 months (July-September 2022). Recurring themes abstracted from the free-text responses from 280 patients correlated with mRS categories as follows: mRS of 0–1 - assistance with cognition, sleep and return to work; mRS of 2 - improvement in functional/motor disability and driving; mRS 3–4 - assistance in recovery from persistent neurologic deficits, and information on novel treatments and interventions. <h3>Conclusions:</h3> We demonstrate the feasibility of standardized and systematic documentation of outcomes in a NeuroRecovery clinic, and the opportunity to identify and develop patient-centric goals for recovery. <b>Disclosure:</b> Mr. Aemaz Ur Rehman has nothing to disclose. Ms. Emerson has nothing to disclose. Dr. Young has nothing to disclose. Dr. Moura has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for eNova. Dr. Moura has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Epilepsy Foundation. The institution of Dr. Moura has received research support from NIH-NIA - 1K08AG053380-01A1. The institution of Dr. Moura has received research support from NIH-NIA 5R01AG062282-02 . The institution of Dr. Moura has received research support from NIH-NIA 2P01AG032952-11 . The institution of Dr. Moura has received research support from NIH- NIA 3R01AG062282-03S1 . The institution of Dr. Moura has received research support from Centers for Diseases Control and Prevention (CDC SIP20-007) . The institution of Dr. Moura has received research support from Epilepsy Foundation of America . Dr. Lin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurotrauma Sciences. Dr. Lin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Encompass Health. Dr. Zafar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Corticare. Dr. Zafar has received research support from NIH.

Curcumin can improve spinal cord injury by inhibiting DNA methylation.

Spinal cord injury (SCI) is a serious central nervous system disease. Traumatic SCI often causes persistent neurological deficits below the injury level. Epigenetic changes occur after SCI. Studies have shown DNA methylation to be a key player in nerve regeneration and remodeling, and in regulating some pathophysiological characteristics of SCI. Curcumin is a natural polyphenol from turmeric. It has anti-inflammatory, antioxidant, and neuroprotective effects, and can mitigate the cell and tissue damage caused by SCI. This report analyzed the specific functions of DNA methylation in central nervous system diseases, especially traumatic brain injury and SCI. DNA methylation can regulate the level of gene expressions in the central nervous system. Therefore, pharmacological interventions regulating DNA methylation may be promising for SCI.

Taste-masked formulation of sodium phenylbutyrate (ACER-001) for the treatment of urea cycle disorders

Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases caused by a deficiency of one of the enzymes or transporters that constitute the urea cycle. Defects in these enzymes lead to acute accumulation (hyperammonemic crises, HAC) or chronically elevated levels (hyperammonemia) of ammonia in the blood and/or various tissues including the brain, which can cause persistent neurological deficits, irreversible brain damage, coma, and death. Ongoing treatment of UCDs include the use of nitrogen-scavenging agents, such as sodium phenylbutyrate (salt of 4-phenylbutyric acid; NaPBA) or glycerol phenylbutyrate (GPB). These treatments provide an alternative pathway for nitrogen disposal through the urinary excretion of phenylacetylglutamine. ACER-001 is a novel formulation of NaPBA with polymer coated pellets in suspension, which is designed to briefly mask the unpleasant bitter taste of NaPBA and is being developed as a treatment option for patients with UCDs. Four Phase 1 studies were conducted to characterize the bioavailability (BA) and/or bioequivalence (BE) of ACER-001 (in healthy volunteers) and taste assessment relative to NaPBA powder (in taste panelists). ACER-001 was shown to be bioequivalent to NaPBA powder under both fed and fasting conditions. Lower systemic exposure of phenylacetate (PAA) and phenylbutyrate (PBA) was observed when ACER-001 was administered with a high-fat meal relative to a fasting state suggesting that the lower doses of PBA administered under fasting conditions may yield similar efficacy with potentially fewer dose dependent adverse effects relative to higher doses with a meal. ACER-001 appeared to be adequately taste-masked, staying below the aversive taste threshold for the first 3min after the formulation was prepared and remaining palatable when taken within 5min.

Correlation of Fall Height, Fracture Severity and Clinical Outcome in Pediatric Supracondylar Fractures—A Retrospective Analysis with an Observation Period of 20 Years

The most common cause leading to supracondylar humerus fractures in children is falling onto an outstretched arm. A correlation between fall height and fracture severity may be assumed but has not yet been described. The aim of this study was to show that fracture severity increases with fall height. Furthermore, the correlation between fracture severity and outcome was examined. A total of 971 children with supracondylar humerus fractures between January 2000 and December 2019 were included in this study. The correlations between fall height and fracture severity and between fracture severity and outcome were assessed. Increasing fall height correlates with fracture severity (p < 0.001; r = 0.24). Furthermore, the incidence of complications increases with fracture severity and a correlation was present accordingly (p < 0.001; r = 0.28). A total of 30 (3.1%) patients showed limitations in range of motion and/or persistent neurologic deficits at the latest follow-up. Type I fractures rarely lead to subsequent limitations. The correlation between increasing fall height and fracture severity was significant. Furthermore, children with type III and IV supracondylar fractures are more likely to develop complications or restrictions in movement than children with type I and II fractures. Hence, the initial fall height may be an indirect indicator of a more or less favorable outcome.

Shunt dependency in supratentorial intraventricular tumors depends on the extent of tumor resection

BackgroundSupratentorial intraventricular tumors (SIVTs) are rare lesions of various entities characteristically presenting with hydrocephalus and often posing a surgical challenge due to their deep-seated localization. We aimed to elaborate on shunt dependency after tumor resection, clinical characteristics, and perioperative morbidity.MethodsWe retrospectively searched the institutional database for patients with supratentorial intraventricular tumors treated at the Department of Neurosurgery of the Ludwig-Maximilians-University in Munich, Germany, between 2014 and 2022.ResultsWe identified 59 patients with over 20 different SIVT entities, most often subependymoma (8/59 patients, 14%). Mean age at diagnosis was 41 ± 3 years. Hydrocephalus and visual symptoms were observed in 37/59 (63%) and 10/59 (17%) patients, respectively. Microsurgical tumor resection was provided in 46/59 patients (78%) with complete resection in 33/46 patients (72%). Persistent postoperative neurological deficits were encountered in 3/46 patients (7%) and generally mild in nature. Complete tumor resection was associated with less permanent shunting in comparison to incomplete tumor resection, irrespective of tumor histology (6% versus 31%, p = 0.025). Stereotactic biopsy was utilized in 13/59 patients (22%), including 5 patients who received synchronous internal shunt implantation for symptomatic hydrocephalus. Median overall survival was not reached and did not differ between patients with or without open resection.ConclusionsSIVT patients display a high risk of developing hydrocephalus and visual symptoms. Complete resection of SIVTs can often be achieved, preventing the need for long-term shunting. Stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms if resection cannot be safely performed. Due to the rather benign histology, the outcome appears excellent when adjuvant therapy is provided.

Calcium pyrophosphate deposition disease mimicking spinal neuroarthropathy.

A 75-year-old male with degenerative joint disease status-post T12-L5 fusion five years ago presented with new-onset left lower extremity weakness. He denied any sensory abnormalities, saddle anaesthesia, or dysfunction of the bladder or bowels. Physical examination was notable for 2/5 left quadriceps and gastrocnemius strength, compared with 5/5 on the right side. CT scan shows erosion and sclerosis of the T10 and T11 end plates with gas within the disk space, consistent with Charcot spinal neuroarthropathy (Fig. 1A). Due to the persistent neurological deficits, the epidural mass was resected and a dural patch graft was placed. Histopathology revealed fibrocartilaginous tissue fragments with degenerative changes and deposition of positively birefringent crystals consistent with calcium pyrophosphate deposition disease (CPPD) (Fig. 1B). One month after resection, the patient’s lower extremity weakness had fully resolved. CPPD can mimic many joint pathologies, including gout and osteoarthritis, in atypical locations. In this case, the radiographic appearance of destruction, debris, distention, disorganization, and density changes resembled Charcot neuroarthropathy but in an unexpected location without the typical antecedent sensory neuropathy [1]. This case illustrates that, when radiographic evidence seems to contradict clinical signs and symptoms of joint disease, clinicians should reserve a high index of suspicion for CPPD [2]. Informed consent has been obtained.

Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury.

Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident astrocytes surrounding the lesion spontaneously transdifferentiate towards a neuronal phenotype. Moreover, this conversion is associated with an increased expression of fibroblast growth factor receptor 4 (Fgfr4), a neural stem cell marker, in astrocytes. Here, we evaluate the therapeutic potential of gene therapy upon Fgfr4 over-expression in mature astrocytes following SCI in adult mice. We found that Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery; however, it may display sexual dimorphism. Improved functional recovery is associated with a decrease in spinal cord lesion volume and reduced glial reactivity. Cell-specific transcriptomic profiling revealed concomitant downregulation of Notch signaling, and up-regulation of neurogenic pathways in converting astrocytes. Our findings suggest that gene therapy targeting Fgfr4 over-expression in astrocytes after injury is a feasible therapeutic approach to improve recovery following traumatism of the spinal cord. Moreover, we stress that a sex-dependent response to astrocytic modulation should be considered for the development of effective translational strategies in other neurological disorders.

Perspectives on rehabilitation, exercise and synaptogenesis after stroke

Strokes are a leading cause of death, persistent neurological deficits, and physical disability worldwide. Exercise-mediated adaptations are an emerging form of therapies that aim to attenuate the severity of post-stroke physical disability; however, there are uncertainties regarding how specific parameters, such as time to initiation and intensity of exercise, affect rehabilitation outcomes. At the cellular level, physical rehabilitation after stroke may enhance post-stroke gluconeogenesis to promote neuroplasticity over cellular damage via hypoxia-inducible factor-1α and exosomes. Furthermore, there is thought to be an optimal time for the initiation of exercise after a stroke, but there is disagreement and uncertainty about this optimal time. This paper discusses the pathophysiology of physical rehabilitation after stroke and reviews current studies on the effects of physical exercise on stroke rehabilitation and plasticity.

Safety and efficacy of brain biopsy: Results from a single institution retrospective cohort study

IntroductionBrain biopsy provides important histopathological diagnostic information for patients with new intracranial lesions. Although a minimally invasive technique, previous studies report an associated morbidity and mortality between 0.6% and 6.8%. We sought to characterise the risk linked to this procedure, and to establish the feasibility of instigating a day-case brain biopsy pathway at our institution. Materials and methodsThis single-centre retrospective case series study included neuronavigation guided mini craniotomy and frameless stereotactic brain biopsies carried out between April 2019 and December 2021. Exclusion criteria were interventions performed for non-neoplastic lesions. Demographic data, clinical and radiological presentation, type of biopsy, histology and complications in the post-operative period were recorded. ResultsData from 196 patients with a mean age of 58.7 years (SD+/-14.4 years) was analysed. 79% (n=155) were frameless stereotactic biopsies and 21% (n=41) neuronavigation guided mini craniotomy biopsies. Complications resulting in acute intracerebral haemorrhage and death, or new persistent neurological deficits were observed in 2% of patients (n=4; 2 frameless stereotactic; 2 open). Less severe complications or transient symptoms were noted in 2.5% of cases (n=5). 8 patients had minor haemorrhages in the biopsy tract with no clinical ramifications. Biopsy was non-diagnostic in 2.5% (n=5) of cases. Two cases were subsequently identified as lymphoma. Other reasons included insufficient sampling, necrotic tissue, and target error. Discussion and conclusionThis study demonstrates that brain biopsy is a procedure with an acceptably low rate of severe complications and mortality, in line with previously published literature. This supports the development of day-case pathway allowing improved patient flow, reducing the risk of iatrogenic complications associated with hospital stay, such as infection and thrombosis.

Tick-Borne Encephalitis: An Update for the Special Operations Forces Provider.

Tick-borne encephalitis (TBE) is a severe disease caused by the tick-borne encephalitis virus (TBEV). TBEV is endemic throughout Eurasia and can cause persistent neurologic deficits and death. Special Operations Forces (SOF) participating in field exercises or operations in TBE-endemic countries are at significantly increased risk of infection. Unlike Lyme disease and other tick-borne illnesses, transmission of TBEV can be immediate, and early tick removal does not reduce the risk of infection. While there are no virus-specific treatments available, the US Food and Drug Administration (FDA) recently approved a TBE vaccine that has yet to be incorporated into formal Department of Defense (DoD) recommendations. SOF medical providers should be aware of this disease entity and consider the TBE vaccine when planning exercises and operations in areas of responsibility (AORs) with TBE-endemic countries. This review serves as a refresher and update on the epidemiology, transmission, and management of TBE for the SOF provider.

An expanded role for surgery in grade 3 1p/19q co-deleted oligodendroglioma.

Grade 3 1p/19q co-deleted oligodendroglioma is an uncommon primary CNS tumor with a high rate of progression and recurrence. This study examines the benefit of surgery after progression and identifies predictors of survival. This is a single-institution retrospective cohort study of consecutive adult patients with anaplastic or grade 3 1p/19q co-deleted oligodendroglioma diagnosed between 2001 and 2020. Eighty patients with 1p/19q co-deleted grade 3 oligodendroglioma were included. The median age was 47 years (interquartile range 38-56) and 38.8% were women. All patients underwent surgery, including gross total resection (GTR) for 26.3% of patients, subtotal resection (STR) for 70.0% of patients, and biopsy for 3.8% of patients. Forty-three cases (53.8%) progressed at a median of 5.6 years, and the median overall survival (OS) was 14.1 years. Among 43 cases of progression or recurrence, 21 (48.8%) underwent another resection. Patients who underwent a second operation had improved OS (P = .041) and survival after progression/recurrence (P = .012), but similar time to subsequent progression as patients who did not have repeat surgery (P = .50). Predictors of mortality at initial diagnosis included a preoperative Karnofsky Performance Status (KPS) under 80 (hazard ratio [HR] 5.4; 95% CI 1.5-19.2), an STR or biopsy rather than GTR (HR 4.1; 95% CI 1.2-14.2), and a persistent postoperative neurologic deficit (HR 4.0; 95% CI 1.2-14.1). Repeat surgery is associated with increased survival, but not time to subsequent progression for progressing or recurrent 1p/19q co-deleted grade 3 oligodendrogliomas recur. Mortality is associated with a preoperative KPS under 80, lack of GTR, and persistent postoperative neurologic deficits after the initial surgery.

Оценка эффективности коррекции шейной спондиломиелопатии у собак

Cervical spondylomyelopathy is a common disease of the cervical spine in dogs of large and giant breeds with an average manifestation period of 7–9 years in the form of dynamic or static compression of the cervical spinal cord and nerve roots, leading to persistent neurological deficit. The aim of this study was to analyze the clinical efficacy of the treatment of cervical spondylomyelopathy in dogs using a distraction intervertebral cage and a fixation plate with complementary threads. The study involved 15 animals with Wobbler syndrome. All patients were operated on with the use of vertebral distraction and their stable fixation. The data of clinical observations in the early and late postoperative periods showed the effectiveness of surgical treatment. Evaluation of the results of surgical treatment after 3 months indicates a trend towards positive dynamics, both in terms of pain relief and gait in thirteen patients (86,7 %). However, only eight patients (53,3 %) achieved full recovery. In two dogs (13,3 %), there was no dynamic recovery of confident movement. Nevertheless, in all patients who underwent surgical stabilization, a positive trend was observed.

547: CEREBRAL EDEMA IN MOG ANTIBODY DISEASE TREATED WITH INVASIVE MULTIMODAL NEUROMONITORING

Introduction: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a neuroinflammatory disorder with a range of clinical phenotypes. MOGAD is typically steroid-responsive, with more refractory cases receiving intravenous immunoglobulin (IVIG) or plasmapheresis. Invasive multimodal neuromonitoring provides real-time measurements of intracranial pressure (ICP) and brain tissue oxygenation (PbtO2) and may be accomplished via insertion of an intraparenchymal probe, also known as a “bolt”. It is becoming an important strategy in the management of patients with traumatic brain injury but is less well described in other acute neurological conditions associated with increased ICP. We describe a case of MOGAD in a child that presented as life-threatening cerebral edema, in which invasive multimodal neuromonitoring with ICP- and PbtO2-directed therapy was employed. This child ultimately survived with some persistent neurological deficits but with normal mood and affect and the ability to eat, drink, and ambulate independently. Description: A 7-year old boy presented with headaches, nausea and somnolence and was found to have increased ICP of unclear etiology. He then progressed to develop exam findings consistent with herniation. He received emergent medical therapies including hypertonic (3%) saline, hyperventilation, and sedation. A bolt was placed for invasive neuromonitoring, which guided treatment based on real-time measurements of ICP and PbtO2. Workup for the etiology of his severe cerebral edema revealed serum MOG antibodies. He received immunomodulatory therapies including steroids, plasmapheresis, and tocilizumab. He was discharged two months later with expressive and receptive aphasia and mild gait imbalance, but with recovered bowel and bladder continence, independent ambulation, and the ability to eat, drink, and interact socially with a normal mood and affect. Discussion: We describe a child who presented with cerebral edema and herniation due to MOGAD. He was managed with invasive multimodal neuromonitoring in addition to standard immunomodulatory treatments and had a favorable outcome. While further data is needed, invasive multimodal neuromonitoring may have utility as an adjunct to standard therapy in children with MOGAD and severe cerebral edema.

Persistent neurological and cerebrovascular deficits following ischemic stroke in a transgenic mouse model of Alzheimer’s disease

AbstractBackgroundTissue nonspecific alkaline phosphatase (TNAP) is one of the most abundant enzymes in brain cerebral microvessels, although its function in human health and disease remains less clear. Our lab has demonstrated that the loss of TNAP activity in cerebral microvessels is linked to diminished blood‐brain barrier function and decreased cerebrovascular integrity in mouse models of sepsis, ischemic stroke, and Alzheimer’s disease (AD). While it is widely known that stroke and AD are comorbid, the relationship between existing AD and its impact on outcomes following ischemic stroke is less clear. The goal of this study was to assess the impact of a moderate cortical ischemic stroke on post‐stroke sensorimotor deficits and AD‐like neuropathology in a mouse model of AD. We hypothesized that post‐stroke loss of TNAP activity is accompanied by a persistent loss of cerebral blood flow (CBF), exacerbated sensorimotor deficits, elevated neuroinflammation, and increased beta‐amyloid deposition.MethodMale and female APPSwID/iNOS‐/‐ (CVN‐AD) mice, 10‐12 months old, were subjected to a cortical photothrombotic stroke (AD+PTS) or sham (AD+sham) surgery and euthanized at seven days post‐stroke. Daily neurological scores, corner test, and rotarod were performed to assess sensorimotor deficits. CBF was assessed by laser speckle contrast imaging (LSCI) prior to euthanasia. Saline‐perfused and 4% paraformaldehyde fixed tissue sections underwent histological staining to quantify infarct volume, cerebral microvessel TNAP activity, and microhemorrhages. Immunostaining assessed astrogliosis, via glial fibrillary acidic protein (GFAP), microgliosis, via Iba‐1, and beta‐amyloid deposition.ResultIschemic stroke impaired performance on the corner test (p=0.0054) and rotarod (p=0.0138) in PTS+AD compared to sham+AD mice. At seven days post‐stroke CBF was diminished (p&lt;0.0001) while Iba‐1 immunolabeling revealed increased microgliosis in the ipsilateral cortex (p&lt;0.0001) and ipsilateral hippocampal CA1 (p=0.0022) in PTS+AD compared to sham+AD mice. A preliminary quantification of TNAP activity in the non‐infarcted ipsilateral hemisphere revealed a trending decrease in PTS+AD mice. No sex differences were observed.ConclusionSensorimotor deficits and microgliosis were increased while CBF was decreased at seven days post‐stroke in PTS+AD compared to sham+AD mice. These and other indices will be compared with age‐matched wild‐type mice in ongoing experiments.

Complications of injections in conservative treatment of degenerative spine disease: a prospective unicentric study

BackgroundSpinal injection has been an accepted part of conservative therapy for degenerative diseases. The drugs used can cause side effects and severe complications. The aim of this study was to determine the occurrence of general side effects (GSE) and complications when performing consecutive different types of spinal injections and to evaluate pain reduction.MethodsProspective data evaluation of patients with degenerative spine disease at hospital admission, discharge, and six and 12 weeks after discharge. All patients received a specific injection protocol depending on their symptoms and radiological findings. The injections performed were dorsal sacroiliac joint injections, perineural injections, epidural interlaminar and epidural periradicular injections, and facet joint injections. Potential complications were categorized and recorded as GSE and complications. In addition, the Numerical Analog Scale (NAS) for pain, the Oswestry Disability Index (ODI) were evaluated.ResultsForty-eight patients were enrolled. There were 282 spinal injections performed. A total of 131 common treatment-related events were recorded. Depending on the type of injection, transient pain at the injection site (32.4–73.5%), radiating pain (9.4–34.7%), and nerve root irritation (2–18.4%) were the most common. One complication with postpuncture syndrome occurred with epidural-interlaminar injection. No persistent neurologic deficits occurred. The highest rate of GSE was observed with periradicular injections (relative frequency (RF) = 0.8), followed by epidural-interlaminar injections (RF = 0.65), least frequently with FJ injections (RF = 0.32). From the time of admission to discharge, NAS scores were significantly decreased and ODI score significantly improved at discharge (p < 0.001), but relapse occurred at the 12-week follow-up.ConclusionsVarious consecutive spinal injections for conservative treatment of degenerative spine diseases are safe and lead to a decrease in pain and improvement in quality of life. GSE are common, but not persistent. Although complications are rare, they can have serious consequences for the patient.

Seizure outcome after resection of insular glioma: a systematic review, meta-analysis, and institutional experience.

Gliomas arising from the insular cortex can be epileptogenic, with a significant proportion of patients having medically refractory epilepsy. The impact of surgery on seizure control for such tumors is not well established. In this study, the authors aimed to investigate seizure outcomes after resection of insular gliomas using a meta-analysis and institutional experience. Three databases (Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) were systematically searched for published studies of seizure outcomes after insular glioma resection from database inception to March 27, 2021. In addition, data were retrospectively collected on all adults (age > 17 years) who had undergone insular glioma resection between June 1997 and June 2015 at the authors' institution. Primary outcome measures were seizure freedom rates at 1 year and the last follow-up. Secondary outcome measures consisted of persistent postoperative neurological deficit beyond 90 days, mortality, and tumor progression or recurrence. Eight studies reporting on 453 patients who had undergone 460 operations were included in the meta-analysis. The pooled mean age of the patients was 42 years. The pooled percentages of patients with extents of resection (EORs) ≥ 90%, 70%-89%, and < 70% were 55%, 33%, and 11%, respectively. The pooled seizure freedom rate at 1 year was 73% for Engel class IA and 78% for Engel class I. The pooled seizure freedom rate at the last follow-up was 60% for Engel class IA and 79% for Engel class I. The pooled percentage of persistent neurological deficit beyond 90 days was 3%. At the authors' institution, 109 patients had undergone resection of insular glioma. A greater EOR was the only significant independent predictor of seizure freedom after surgery (HR 0.290, p = 0.017). The optimal threshold for seizure freedom corresponded to an EOR of 81%. Patients with an EOR > 81% had a significantly higher seizure freedom rate (OR 2.16, p = 0.048). Maximal safe resection can be performed with minimal surgical morbidity to achieve favorable seizure freedom rates in both the short and long term. When gross-total resection is not possible, an EOR > 81% confers the greatest sensitivity and specificity for achieving seizure freedom. Systematic review registration no.: CRD42021249404 (https://www.crd.york.ac.uk/prospero/).