Seizures and antiepileptic drugs in patients with spontaneous intracerebral hemorrhages

AbstractPurposePatients with intracerebral hemorrhage (ICH) are often initiated on antiepileptic drugs without a clear indication. We compared the percentage of patients with spontaneous ICH who had seizures at onset or during hospitalization, and examined empiric use of antiepileptic drugs (AEDs) in these patients in 2 cohorts 10 years apart.MethodsUsing a clinical data registry at a tertiary care adult hospital, we retrospectively selected admissions for spontaneous ICH between 1/1/99–12/31/00 (Cohort A, n=30) and 1/1/09–12/31/10 (Cohort B, n=108). Clinical, neurophysiological and radiological data were collected in both cohorts.ResultsIn Cohorts A and B respectively, AEDs were started in 53.3% and 50.0%, and continued on discharge in 50.0% and 20.4% of patients; 86.6% and 59.1% of patients discharged on AEDs did not have a clinical/electrographic seizure or epileptiform EEG findings. Seizures occurred in 6.6% and 13.0% in Cohorts A and B respectively. The presence of a seizure at presentation (p=0.01) and during hospitalization (p=0.02) were predictors for continuing AED on discharge.ConclusionIn both cohorts, a significant number of patients were discharged on AEDs without a clear indication, though there is a change in practice between the two cohorts

Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19-A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium.

Importance The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome. Objective To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19. Design, Setting, and Participants This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation. Exposures Clinically diagnosed or laboratory-confirmed COVID-19. Main Outcomes and Measures Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospital mortality. Results Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the mean age was 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the mean age was 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reported neurological symptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The most prevalent neurological signs and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), while meningitis and/or encephalitis were rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death (adjusted odds ratio [aOR], 5.99; 95% CI, 4.33-8.28) after adjusting for study site, age, sex, race, and ethnicity. Presence of preexisting neurological disorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19. Conclusions and Relevance In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexisting neurological disorders were associated with increased risk of developing neurological signs and/or syndromes in COVID-19

Common Data Elements for COVID-19 Neuroimaging: A GCS-NeuroCOVID Proposal

Funder: National Institute of Neurological Disorders and Stroke; doi: http://dx.doi.org/10.13039/100000065Funder: James S. McDonnell Foundation; doi: http://dx.doi.org/10.13039/100000913Funder: National Institute of Health ResearchFunder: United Kingdom Research and InnovationFunder: Addenbrooke’s Charitable Trus

Social support and Quality of Life: a cross-sectional study on survivors eight months after the 2008 Wenchuan earthquake

<p>Abstract</p> <p>Background</p> <p>The 2008 Wenchuan earthquake resulted in extensive loss of life and physical and psychological injuries for survivors. This research examines the relationship between social support and health-related quality of life for the earthquake survivors.</p> <p>Methods</p> <p>A multistage cluster sampling strategy was employed to select participants from 11 shelters in nine counties exposed to different degrees of earthquake damage, for a questionnaire survey. The participants were asked to complete the Short Form 36 and the Social Support Rating Scale eight months after the earthquake struck. A total of 1617 participants returned the questionnaires. The quality of life of the survivors (in the four weeks preceding the survey) was compared with that of the general population in the region. Multivariate logistic regression analysis and canonical correlation analysis were performed to determine the association between social support and quality of life.</p> <p>Results</p> <p>The earthquake survivors reported poorer quality of life than the general population, with an average of 4.8% to 19.62% reduction in scores of the SF-36 (p < 0.001). The multivariate logistic regression analysis showed that those with stronger social support were more likely to have better quality of life. The canonical correlation analysis found that there was a discrepancy between actual social support received and perceived social support available, and the magnitude of this discrepancy was inversely related to perceived general health (rs = 0.467), and positively related to mental health (rs = 0.395).</p> <p>Conclusion</p> <p>Social support is associated with quality of life in the survivors of the earthquake. More attention needs to be paid to increasing social support for those with poorer mental health.</p

Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: Evaluation, management, and scientific questions

Background: Vaccine induced immune medicated thrombocytopenia or VITT, is a recent and rare phenomenon of thrombosis with thrombocytopenia, frequently including cerebral venous thromboses (CVT), that has been described following vaccination with adenovirus vaccines ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2.S Johnson and Johnson (Janssen/J&J). The evaluation and management of suspected cases of CVT post COVID-19 vaccination are critical skills for a broad range of healthcare providers. Methods: A collaborative comprehensive review of literature was conducted among a global group of expert neurologists and hematologists. Findings: Strategies for rapid evaluation and treatment of the CVT in the context of possible VITT exist, including inflammatory marker measurements, PF4 assays, and non-heparin anticoagulation. Interpretation: There are many unanswered questions regarding cases of CVT, possibly in association with VITT. Public health specialists should explore ways to enhance public and professional education, surveillance, and reporting of this syndrome to reduce its impact on health and global vaccination efforts. Funding: Non

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Biospecimens and Molecular and Cellular Biomarkers in Aneurysmal Subarachnoid Hemorrhage Studies : Common Data Elements and Standard Reporting Recommendations

INTRODUCTION: Development of clinical biomarkers to guide therapy is an important unmet need in aneurysmal subarachnoid hemorrhage (SAH). A wide spectrum of plausible biomarkers has been reported for SAH, but none have been validated due to significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints. METHODS: A systematic review of SAH biomarkers was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The panel's recommendations focused on harmonization of (1) target cellular and molecular biomarkers for future investigation in SAH, (2) standardization of best-practice procedures in biospecimen and biomarker studies, and (3) experimental method reporting requirements to facilitate meta-analyses and future validation of putative biomarkers. RESULTS: No cellular or molecular biomarker has been validated for inclusion as "core" recommendation. Fifty-four studies met inclusion criteria and generated 33 supplemental and emerging biomarker targets. Core recommendations include best-practice protocols for biospecimen collection and handling as well as standardized reporting guidelines to capture the heterogeneity and variabilities in experimental methodologies and biomarker analyses platforms. CONCLUSION: Significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints exist in SAH biomarker studies and present significant barriers toward validation and translation of putative biomarkers to clinical use. Adaptation of common data elements, recommended biospecimen protocols, and reporting guidelines will reduce heterogeneity and facilitate future meta-analyses and development of validated clinical biomarkers in SAH

Biospecimens and Molecular and Cellular Biomarkers in Aneurysmal Subarachnoid Hemorrhage Studies: Common Data Elements and Standard Reporting Recommendations

INTRODUCTION: Development of clinical biomarkers to guide therapy is an important unmet need in aneurysmal subarachnoid hemorrhage (SAH). A wide spectrum of plausible biomarkers has been reported for SAH, but none have been validated due to significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints. METHODS: A systematic review of SAH biomarkers was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The panel's recommendations focused on harmonization of (1) target cellular and molecular biomarkers for future investigation in SAH, (2) standardization of best-practice procedures in biospecimen and biomarker studies, and (3) experimental method reporting requirements to facilitate meta-analyses and future validation of putative biomarkers. RESULTS: No cellular or molecular biomarker has been validated for inclusion as "core" recommendation. Fifty-four studies met inclusion criteria and generated 33 supplemental and emerging biomarker targets. Core recommendations include best-practice protocols for biospecimen collection and handling as well as standardized reporting guidelines to capture the heterogeneity and variabilities in experimental methodologies and biomarker analyses platforms. CONCLUSION: Significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints exist in SAH biomarker studies and present significant barriers toward validation and translation of putative biomarkers to clinical use. Adaptation of common data elements, recommended biospecimen protocols, and reporting guidelines will reduce heterogeneity and facilitate future meta-analyses and development of validated clinical biomarkers in SAH