Dementia after Ischemic Stroke, from Molecular Biomarkers to Therapeutic Options.

Ischemic stroke is a leading cause of disability worldwide. While much of post-stroke recovery is focused on physical rehabilitation, post-stroke dementia (PSD) is also a significant contributor to poor functional outcomes. Predictive tools to identify stroke survivors at risk for the development of PSD are limited to brief screening cognitive tests. Emerging biochemical, genetic, and neuroimaging biomarkers are being investigated in an effort to unveil better indicators of PSD. Additionally, acetylcholinesterase inhibitors, NMDA receptor antagonists, dopamine receptor agonists, antidepressants, and cognitive rehabilitation are current therapeutic options for PSD. Focusing on the chronic sequelae of stroke that impair neuroplasticity highlights the need for continued investigative trials to better assess functional outcomes in treatments targeted for PSD.

Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies.

Stroke is a major cause of death and disability worldwide. Endovascular thrombectomy has been impactful in decreasing mortality. However, many clinical results continue to show suboptimal functional outcomes despite high recanalization rates. This gap in recanalization and symptomatic improvement suggests a need for adjunctive therapies in post-thrombectomy care. With greater insight into ischemia-reperfusion injury, recent preclinical testing of neuroprotective agents has shifted towards preventing oxidative stress through upregulation of antioxidants and downstream effectors, with positive results. Advances in multiple neuroprotective therapies, including uric acid, activated protein C, nerinetide, otaplimastat, imatinib, verapamil, butylphthalide, edaravone, nelonemdaz, ApTOLL, regional hypothermia, remote ischemic conditioning, normobaric oxygen, and especially nuclear factor erythroid 2-related factor 2, have promising evidence for improving stroke care. Sedation and blood pressure management in endovascular thrombectomy also play crucial roles in improved stroke outcomes. A hand-in-hand approach with both endovascular therapy and neuroprotection may be the key to targeting disability due to stroke.

Perioperative cognition in association with malnutrition and frailty: a narrative review.

Postoperative delirium (POD) is a prevalent clinical entity characterized by reversible fluctuating altered mental status and cognitive impairment with acute and rapid onset a few days after major surgery. Postoperative cognitive decline (POCD) is a more permanent extension of POD characterized by prolonged global cognitive impairment for several months to years after surgery and anesthesia. Both syndromes have been shown to increase morbidity and mortality in postoperative patients making their multiple risk factors targets for optimization. In particular, nutrition imparts a significant and potentially reversible risk factor. Malnutrition and frailty have been linked as risk factors and predictive indicators for POD and less so for POCD. This review aims to outline the association between nutrition and perioperative cognitive outcomes as well as potential interventions such as prehabilitation.

Eye Tracking as a Biomarker for Concussion in Children.

OBJECTIVE: Concussion is the most common type of brain injury in both pediatric and adult populations and can potentially result in persistent postconcussion symptoms. Objective assessment of physiologic "mild" traumatic brain injury in concussion patients remains challenging. This study evaluates an automated eye-tracking algorithm as a biomarker for concussion as defined by its symptoms and the clinical signs of convergence insufficiency and accommodation dysfunction in a pediatric population. DESIGN: Cross-sectional case-control study. SETTING: Primary care. PATIENTS: Concussed children (N = 56; mean age = 13 years), evaluated at a mean of 22-week post-injury, compared with 83 uninjured controls. INDEPENDENT VARIABLES: Metrics comparing velocity and conjugacy of eye movements over time were obtained and were compared with the correlation between Acute Concussion Evaluation (ACE) scores, convergence, and accommodation dysfunction. MAIN OUTCOME MEASURES: Subjects' eye movements recorded with an automated eye tracker while they watched a 220-second cartoon film clip played continuously while moving within an aperture. RESULTS: Twelve eye-tracking metrics were significantly different between concussed and nonconcussed children. A model to classify concussion as diagnosed by its symptoms assessed using the ACE achieved an area under the curve (AUC) = 0.854 (71.9% sensitivity, 84.4% specificity, a cross-validated AUC = 0.789). An eye-tracking model built to identify near point of convergence (NPC) disability achieved 95.8% specificity and 57.1% sensitivity for an AUC = 0.810. Reduced binocular amplitude of accommodation had a Spearman correlation of 0.752(P value <0.001) with NPC. CONCLUSION: Eye tracking correlated with concussion symptoms and detected convergence and accommodative abnormalities associated with concussion in the pediatric population. It demonstrates utility as a rapid, objective, noninvasive aid in the diagnosis of concussion.

High prevalence of prior contact sports play and concussion among orthopedic and neurosurgical department chairs.

OBJECTIVE Increased understanding of the consequences of traumatic brain injury has heightened concerns about youth participation in contact sports. This study investigated the prevalence of high school and collegiate contact sports play and concussion history among surgical department chairs. METHODS A cross-sectional survey was administered to 107 orthopedic and 74 neurosurgery chairs. Responses were compared to published historical population norms for contact sports (high school 27.74%, collegiate 1.44%), football (high school 10.91%, collegiate 0.76%), and concussion prevalence (12%). One-proportion Z-tests, chi-square tests, and binary logistic regression were used to analyze differences. RESULTS High school contact sports participation was 2.35-fold higher (65.3%, p < 0.001) for orthopedic chairs and 1.73-fold higher (47.9%, p = 0.0018) for neurosurgery chairs than for their high school peers. Collegiate contact sports play was 31.0-fold higher (44.7%, p < 0.001) for orthopedic chairs and 15.1-fold higher (21.7%, p < 0.001) for neurosurgery chairs than for their college peers. Orthopedic chairs had a 4.30-fold higher rate of high school football participation (46.9%, p < 0.001) while neurosurgery chairs reported a 3.05-fold higher rate (33.3%, p < 0.001) than their high school peers. Orthopedic chairs reported a 28.1-fold higher rate of collegiate football participation (21.3%, p < 0.001) and neurosurgery chairs reported an 8.58-fold higher rate (6.5%, p < 0.001) compared to their college peers. The rate at which orthopedic (42.6%, p < 0.001) and neurosurgical (42.4%, p < 0.001) chairs reported having at least 1 concussion in their lifetime was significantly higher than the reported prevalence in the general population. After correction for worst possible ascertainment bias, all results except high school contact sports participation remained significant. CONCLUSIONS The high prevalence of youth contact sports play and concussion among surgical specialty chairs affirms that individuals in careers requiring high motor and cognitive function frequently played contact sports. The association highlights the need to further examine the relationships between contact sports and potential long-term benefits as well as risks of sport-related injury.

Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip.

OBJECTIVE The precise threshold differentiating normal and elevated intracranial pressure (ICP) is variable among individuals. In the context of several pathophysiological conditions, elevated ICP leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (CNs), either or both of which may contribute to ocular dysmotility. The purpose of this study was to assess the impact of elevated ICP on eye-tracking performed while patients were watching a short film clip. METHODS Awake patients requiring placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video moving around the perimeter of a viewing monitor. Pupil position was recorded at 500 Hz and metrics associated with each eye individually and both eyes together were calculated. Linear regression with generalized estimating equations was performed to test the association of eye-tracking metrics with changes in ICP. RESULTS Eye tracking was performed at ICP levels ranging from -3 to 30 mm Hg in 23 patients (12 women, 11 men, mean age 46.8 years) on 55 separate occasions. Eye-tracking measures correlating with CN function linearly decreased with increasing ICP (p < 0.001). Measures for CN VI were most prominently affected. The area under the curve (AUC) for eye-tracking metrics to discriminate between ICP < 12 and ≥ 12 mm Hg was 0.798. To discriminate an ICP < 15 from ≥ 15 mm Hg the AUC was 0.833, and to discriminate ICP < 20 from ≥ 20 mm Hg the AUC was 0.889. CONCLUSIONS Increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching a short film clip. These results suggest that eye tracking may be used as a noninvasive, automatable means to quantitate the physiological impact of elevated ICP, which has clinical application for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome.

Assessment of acute head injury in an emergency department population using sport concussion assessment tool - 3rd edition.

Sport Concussion Assessment Tool version 3 (SCAT-3) is one of the most widely researched concussion assessment tools in athletes. Here normative data for SCAT3 in nonathletes are presented. The SCAT3 was administered to 98 nonathlete healthy controls, as well as 118 participants with head-injury and 46 participants with other body trauma (OI) presenting to the ED. Reference values were derived and classifier functions were built to assess the accuracy of SCAT3. The control population had a mean of 2.30 (SD = 3.62) symptoms, 4.38 (SD = 8.73) symptom severity score (SSS), and 26.02 (SD = 2.52) standardized assessment of concussion score (SAC). Participants were more likely to be diagnosed with a concussion (from among healthy controls) if the SSS > 7; or SSS ≤ 7 and SAC ≤22 (sensitivity = 96%, specificity = 77%). Identification of head injury patients from among both, healthy controls and body trauma was possible using rule SSS > 7 and headache or pressure in head present, or SSS ≤ 7 and SAC ≤ 22 (sensitivity = 87%, specificity = 80%). In this current study, the SCAT-3 provided high sensitivity to discriminate acute symptoms of TBI in the ED setting. Individuals with a SSS > 7 and headache or pressure in head, or SSS ≤ 7 but with a SAC ≤ 22 within 48-hours of an injury should undergo further testing.