Biomarker Application for Precision Medicine in Stroke

Stroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this comprehensive review, we propose that future biomarker studies can be designed to support precision medicine therapeutic interventions after stroke. The current challenges in defining ideal biomarkers for stroke are highlighted, including consideration of disease course, age, lifestyle factors, and subtypes of stroke. This overview of current clinical trials includes biomarker collection, and concludes with an example of biomarker design for aneurysmal subarachnoid hemorrhage. With the advent of -omics studies, neuroimaging, big data, and precision medicine, well-designed stroke biomarker trials will greatly advance the treatment of a disease that affects millions globally every year

Delayed Diagnosis in Cerebral Venous Thrombosis: Associated Factors and Clinical Outcomes.

Background Identifying factors associated with delayed diagnosis of cerebral venous thrombosis (CVT) can inform future strategies for early detection. Methods and Results We conducted a retrospective cohort study including all participants from ACTION-CVT (Anticoagulation in the Treatment of Cerebral Venous Thrombosis) study who had dates of neurologic symptom onset and CVT diagnosis available. Delayed diagnosis was defined as CVT diagnosis occurring in the fourth (final) quartile of days from symptom onset. The primary study outcome was modified Rankin Scale score of ≤1 at 90 days; secondary outcomes included partial/complete CVT recanalization on last available imaging and modified Rankin Scale score of ≤2. Logistic regression analyses were used to identify independent variables associated with delayed diagnosis and to assess the association of delayed diagnosis and outcomes. A total of 935 patients were included in our study. Median time from symptom onset to diagnosis was 4 days (interquartile range, 1-10 days). Delayed CVT diagnosis (time to diagnosis >10 days) occurred in 212 patients (23%). Isolated headache (adjusted odds ratio [aOR], 2.36 [95% CI, 1.50-3.73]; P10 days after symptom onset. Delayed CVT diagnosis was associated with the symptom of isolated headache and was not associated with adverse clinical outcomes

Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. METHODS We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. RESULTS Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60-187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.07), male sex (OR, 0.44; 95% CI, 0.24-0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29-0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. CONCLUSION Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings

Outcome Prediction in Cerebral Venous Thrombosis: The IN-REvASC Score.

BACKGROUND We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). METHODS We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. RESULTS A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03). CONCLUSIONS Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials

Volume 09

Introduction Dr. Roger A. Byrne Islamic Radicalization of Women in The United Kingdom by Mackenzie Adamson Harmony by Chad Benton The Rhetoric of Distrust: A Dangerous Game During the 2016 Presidential Campaign by Garrett Badgley Neither Man nor Monster: Frankenstein\u27s Creature as Posthuman by Anna Bultrowicz Holisticrx by Kelsey Daniel Reality Bytes: Identity in the Virtual World of Ernest Cline\u27s Ready Player One by Taylor Embrey Animation by Jose Romero Sue Klebold\u27s a Mother\u27s Reckoning: A Call to Action for Mental Health Advocacy by Taylor Hughes Hillary Clinton\u27s Rhetoric of Gender Inequality: The Past, the Present, nd the (Hypothetical) Future by Haley Klepatzki Against the Grain: Eat Gluten Free by Emily Spittle Following Judith: A Midrashic Approach to the Book of Judith by Kelsey Longnaker Identity and Dialect Adaptation: The Effect of Geography and Community on Dialect by Alexis Paige Manuel These are the Gardens Of The Desert : The Revolutionary Impact Of Bryant\u27s The Prairies on American Literature by Montana Nelson Beauty is Pain: Eating Disorders, Gender, and the Lies We Feed Young Women By Faith Shelton Be a Man: The Eradication of Gender in Y: The Last Man by Joseph Stearman A Computational Study of Molecular Electronics: The Role of Molecular Structure by John Brumfield The Importance of Voting by Monica Mcgraw Method for The Detection and Removal of Antibiotics in Bottled Water by Jayden Metzger Small Chimp Print by Maddie Smith Mental Health Impairments in Rural Communities by Lyndsey Swinhart F@#* That: The Effects of Swearing and Influence of Authority on Stress Level by Amanda N. Chappell And Haley C. Moore Friend or Faux? Prosocial and Antisocial Social Media Use and Personality Traits by Samantha Burgess, Heather Dunbar, Briana Hackett, Jackie Mcmillion, Kiana Simpkins, And Ta\u27miya Vanhook-Davis There\u27s Someone in My Head but It’s Not Me : Attitudes About Diagnosis and Treatment of Psychological Disorders by Kiana Simpkins, Lindsey Sparrock, And Leonie Verstraete Efflorescent Bonds by Kristen Melton Shower Thoughts by Ryan Bultrowic

Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia

plan (drawing), cloister with the church (drawing from Letarouilly, 1840

Post-stroke blood-brain barrier disruption and poor functional outcome in patients receiving thrombolytic therapy

Background and Purpose: The role played by post-stroke inflammation after an ischemic event in limiting functional recovery remains unclear. One component of post-stroke inflammation is disruption of the blood-brain barrier (BBB). This study examines the relationship between post-stroke BBB disruption and functional outcome. Methods: Acute stroke patients treated with thrombolysis underwent magnetic resonance imaging scanning 24 h and 5 days after their initial event. BBB permeability maps were generated from perfusion weighted imaging. Average permeability was calculated in the affected hemisphere. Good functional outcome, defined as a modified Rankin score of 0 or 1, was compared with average permeability using logistic regression. Results: Of the 131 patients enrolled, 76 patients had the necessary data to perform the analysis at 24 h, and 58 -patients had data for the 5-day assessment. Higher BBB permeability measured at 24 h (OR 0.57; 95% CI 0.33-0.99, p = 0.045) and at 5 days (OR 0.24; 95% CI 0.09-0.66, p = 0.005) was associated with worse functional outcome 1-3 months after the acute ischemic stroke. For every percentage increase in BBB disruption at 5 days, there was a 76% decrease in the chance of achieving a good functional outcome after stroke. Multivariate analysis found this to be independent of age, stroke volume, or clinical stroke severity. Conclusions: Post-stroke BBB disruption appears to be predictive of functional outcome irrespective of stroke size

Recurrent thrombolysis of a stuttering lacunar infarction captured on serial MRIs

Lacunar strokes account for about a fourth of all ischemic strokes. Pontine infarcts often present with stuttering symptoms, referred to as pontine warning syndrome (PWS). Patients presenting with fluctuating symptoms can appear to have rapidly improving symptoms and thus often go untreated despite the risk of recurrent deficits. MRI carries a higher sensitivity in detecting posterior circulation strokes compared to computed topagraphy, but does not always indicate irreversible injury. Here we present the first description of a stuttering lacune, captured radiographically on serial magnetic resonance imaging (MRI), that was initially averted with the administration of intravenous (IV) tissue plasminogen activator (tPA), only to return a month later and progress on imaging despite re-administration of tPA. During the first admission, our patient had spontaneous resolution of symptoms with complete reversal on restricted diffusion soon after IV tPA administration. On the second admission, the stuttering symptoms returned as did the same pontine lesion. Although his stuttering lesions lasted for several days, and the pontine lesion did ultimately progress to partial infarction on MRI, he was discharged home without neurologic deficits. Our case suggests that tPA may be of benefit in patients with lacunar pontine strokes even if symptoms rapidly improve or resolve. Keywords: Thrombolysis, Ischemic stroke, Lacunar infarct, MRI, Small vessel disease, Rapidly improving stroke symptoms, Ischemic toleranc