scholarly journals Biomarker Application for Precision Medicine in Stroke

2019 ◽  
Vol 11 (4) ◽  
pp. 615-627 ◽  
Author(s):  
Alexis N. Simpkins ◽  
Miroslaw Janowski ◽  
Helieh S. Oz ◽  
Jill Roberts ◽  
Gregory Bix ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Hemorrhagic Stroke ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Stroke Survivor ◽  
Lifestyle Factors ◽  
Stroke Recovery ◽  
Therapeutic Interventions ◽  
Disease Course ◽  
Comprehensive Review

AbstractStroke 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.

scholarly journals Rehabilitation following hemorrhagic stroke: building the case for stroke-subtype specific recovery therapies

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2044 ◽  
Author(s):  
Tomoko Kitago ◽  
Rajiv R. Ratan
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Functional Recovery ◽  
Hemorrhagic Stroke ◽  
Current Understanding ◽  
Stroke Recovery ◽  
Stroke Subtype ◽  
The Brain ◽  
Significant Mortality

Intracerebral hemorrhage (ICH), a form of brain bleeding and minor subtype of stroke, leads to significant mortality and long-term disability. There are currently no validated approaches to promote functional recovery after ICH. Research in stroke recovery and rehabilitation has largely focused on ischemic stroke, but given the stark differences in the pathophysiology between ischemic and hemorrhagic stroke, it is possible that strategies to rehabilitate the brain in distinct stroke subtypes will be different. Here, we review our current understanding of recovery after primary intracerebral hemorrhage with the intent to provide a framework to promote novel, stroke-subtype specific approaches.

scholarly journals Clinical Use of Surface Electromyography to Track Acute Upper Extremity Muscle Recovery after Stroke: A Descriptive Case Study of a Single Patient

2021 ◽  
Vol 4 (2) ◽  
pp. 32
Author(s):  
Heather A. Feldner ◽  
Christina Papazian ◽  
Keshia M. Peters ◽  
Claire J. Creutzfeldt ◽  
Katherine M. Steele
Keyword(s):  
Muscle Activity ◽  
Surface Electromyography ◽  
Inpatient Rehabilitation ◽  
Stroke Survivor ◽  
Structured Interview ◽  
Routine Care ◽  
Stroke Recovery ◽  
Descriptive Case Study ◽  
Sensing Technology

Arm recovery varies greatly among stroke survivors. Wearable surface electromyography (sEMG) sensors have been used to track recovery in research; however, sEMG is rarely used within acute and subacute clinical settings. The purpose of this case study was to describe the use of wireless sEMG sensors to examine changes in muscle activity during acute and subacute phases of stroke recovery, and understand the participant’s perceptions of sEMG monitoring. Beginning three days post-stroke, one stroke survivor wore five wireless sEMG sensors on his involved arm for three to four hours, every one to three days. Muscle activity was tracked during routine care in the acute setting through discharge from inpatient rehabilitation. Three- and eight-month follow-up sessions were completed in the community. Activity logs were completed each session, and a semi-structured interview occurred at the final session. The longitudinal monitoring of muscle and movement recovery in the clinic and community was feasible using sEMG sensors. The participant and medical team felt monitoring was unobtrusive, interesting, and motivating for recovery, but desired greater in-session feedback to inform rehabilitation. While barriers in equipment and signal quality still exist, capitalizing on wearable sensing technology in the clinic holds promise for enabling personalized stroke recovery.

scholarly journals Rupture Risk of Intracranial Aneurysm and Prediction of Hemorrhagic Stroke after Liver Transplant

2021 ◽  
Vol 11 (4) ◽  
pp. 445
Author(s):  
Hye-Mee Kwon ◽  
In-Gu Jun ◽  
Kyoung-Sun Kim ◽  
Young-Jin Moon ◽  
In Young Huh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intracranial Aneurysm ◽  
Hemorrhagic Stroke ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Hazard Analysis ◽  
Related Data ◽  
Incidence And Mortality ◽  
Before And After ◽  
History Of ◽  
Cirrhotic Patients

Postoperative hemorrhagic stroke (HS) is a rare yet devastating complication after liver transplantation (LT). Unruptured intracranial aneurysm (UIA) may contribute to HS; however, related data are limited. We investigated UIA prevalence and aneurysmal subarachnoid hemorrhage (SAH) and HS incidence post-LT. We identified risk factors for 1-year HS and constructed a prediction model. This study included 3544 patients who underwent LT from January 2008 to February 2019. Primary outcomes were incidence of SAH, HS, and mortality within 1-year post-LT. Propensity score matching (PSM) analysis and Cox proportional hazard analysis were performed. The prevalence of UIAs was 4.63% (n = 164; 95% confidence interval (CI), 3.95–5.39%). The 1-year SAH incidence was 0.68% (95% CI, 0.02–3.79%) in patients with UIA. SAH and HS incidence and mortality were not different between those with and without UIA before and after PSM. Cirrhosis severity, thrombocytopenia, inflammation, and history of SAH were identified as risk factors for 1-year HS. UIA presence was not a risk factor for SAH, HS, or mortality in cirrhotic patients post-LT. Given the fatal impact of HS, a simple scoring system was constructed to predict 1-year HS risk. These results enable clinical risk stratification of LT recipients with UIA and help assess perioperative HS risk before LT.

scholarly journals Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident

2021 ◽  
Vol 22 (15) ◽  
pp. 7847
Author(s):  
Anthony Fringuello ◽  
Philip D. Tatman ◽  
Tadeusz Wroblewski ◽  
John A. Thompson ◽  
Xiaoli Yu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Hemorrhagic Stroke ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Interleukin 7 ◽  
Poor Outcomes ◽  
Patient Prognosis ◽  
The Brain

Background: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines—many associated with worse outcomes—occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood–brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. Methods: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). Results: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. Conclusions: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery.

scholarly journals Tofacitinib: An Option for Acute Severe Ulcerative Colitis?

2021 ◽  
pp. 1-3
Author(s):  
Sara Santos ◽  
Verónica Gamelas ◽  
Rita Saraiva ◽  
Guilherme Simões ◽  
Joana Saiote ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Improvement ◽  
Rescue Therapy ◽  
New Drugs ◽  
Multiple Drug ◽  
Disease Course ◽  
Efficacy And Safety ◽  
Severe Ulcerative Colitis ◽  
Rapid Absorption

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.

scholarly journals Letter: Predicting Long-Term Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage Using Decision Tree Modeling

Neurosurgery ◽  
2020 ◽  
Author(s):  
Jaskaran Singh Gosal ◽  
Kuntal Kanti Das ◽  
Deepak Khatri ◽  
Kamlesh Singh Bhaisora ◽  
Sanjay Behari
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Decision Tree ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Long Term Outcomes ◽  
Poor Grade ◽  
Tree Modeling

A review of current and future medical therapies for cerebral vasospasm following aneurysmal subarachnoid hemorrhage

2006 ◽  
Vol 21 (3) ◽  
pp. 1-7 ◽  
Author(s):  
J Mocco ◽  
Brad E. Zacharia ◽  
Ricardo J. Komotar ◽  
E. Sander Connolly
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Relevant Literature ◽  
Therapeutic Interventions ◽  
Common Complication ◽  
Current State ◽  
Threefold Increase ◽  
Poor Understanding ◽  
Medical Therapies

✓In an effort to help clarify the current state of medical therapy for cerebral vasospasm, the authors reviewed the relevant literature on the established medical therapies used for cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH), and they discuss burgeoning areas of investigation. Despite advances in the treatment of aneurysmal SAH, cerebral vasospasm remains a common complication and has been correlated with a 1.5- to threefold increase in death during the first 2 weeks after hemorrhage. A number of medical, pharmacological, and surgical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Although much has been elucidated regarding its pathophysiology, the treatment of cerebral vasospasm remains a dilemma. Although a poor understanding of SAH-induced cerebral vasospasm pathophysiology has, to date, hampered the development of therapeutic interventions, current research efforts promise the eventual production of new medical therapies.

α-Oxoaldehyde metabolism and diabetic complications

2003 ◽  
Vol 31 (6) ◽  
pp. 1358-1363 ◽  
Author(s):  
P.J. Beisswenger ◽  
S.K. Howell ◽  
R.G. Nelson ◽  
M. Mauer ◽  
B.S. Szwergold
Keyword(s):  
Diabetic Complications ◽  
Complex Mixture ◽  
Therapeutic Interventions ◽  
Diabetic Patients ◽  
Human Populations ◽  
Control Mechanisms ◽  
Protective Mechanisms ◽  
Glycation End Products ◽  
End Products

The factors responsible for variable susceptibility to diabetic nephropathy are not clear. According to the non-enzymatic glycation hypothesis, diabetes-related tissue damage occurs due to a complex mixture of toxic products, including α-oxoaldehydes, which are inherently toxic as well as serving as presursors for advanced glycation end-products. Protective mechanisms exist to control this unavoidable glycation, and these are determined by genetic or environmental factors that can regulate the concentrations of the reactive sugars or end-products. In diabetes these protective mechanisms become more important, since glycation stress increases, and less efficient defence systems against this stress could lead to diabetic complications. Some of these enzymatic control mechanisms, including those that regulate α-oxoaldehydes, have been identified. We have observed significant increases in production of the α-oxoaldehydes methylglyoxal and 3-deoxyglucosone in three human populations with biopsy-proven progression of nephropathy. The increase in methylglyoxal could be secondary to defects in downstream glycolytic enzymes (such as glyceraldehyde-3-phosphate dehydrogenase) that regulate its production, or in detoxification mechanisms such as glyoxalase. Other mechanisms, however, appear to be responsible for the observed increase in 3-deoxyglucosone levels. We present results of our studies on the mechanisms responsible for variable production of α-oxoaldehydes by measuring the activity and characteristics of these enzymes in cells from complication-prone and -resistant diabetic patients. New therapeutic interventions designed to control these endogenous mechanisms could potentially enhance protection against excessive glycation and prevent or reverse complications of long-term diabetes.

Abstract 176: Long Term Mortality in Acute Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation According to Location and Burden of Cerebral Microbleeds

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tae-Jin Song ◽  
Jinkwon Kim ◽  
Dongbeom Song ◽  
Yong-Jae Kim ◽  
Hyo Suk Nam ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Hemorrhagic Stroke ◽  
Independent Predictor ◽  
Stroke Patients ◽  
Risk Of Death ◽  
Long Term Mortality

Background: Cerebral microbleeds (CMBs) were predictive of mortality in elderly and considered as a putative marker for risk of intracranial hemorrhage. Stroke patients with non valvular atrial fibrillation (NVAF) require anticoagulation, which increases the risk of hemorrhages. We investigated association of CMBs with the long term mortality in acute ischemic stroke patients with NVAF. Methods: During 6 years , consecutive ischemic stroke patients who had NVAF and who had undergone brain MRI with a gradient-recalled echo sequence were enrolled. Long-term mortality and causes of death were identified using data from Korean National Statistical Office. Survival analysis was performed whether the presence, number and location of CMBs were related with all causes, cardiovascular, and cerebrovascular mortality during follow-up. Results: Total 506 patients were enrolled during the study period and were followed up for median 2.5 years. CMBs were found in 30.8% of patients (156/506). Oral anticoagulation with warfarin was prescribed at discharge in 477 (82.7%) patients. During follow up, 177 (35%) patients died and cerebrovascular death was noted in 93 patients (81 ischemic stroke and 12 hemorrhagic stroke). After adjusting age, sex and significant variables in univariate analysis (p<0.1), multiple CMBs (≥5) were the independent predictor for all-cause, cardiovascular and ischemic stroke mortalities. The strictly lobar CMBs were associated with hemorrhagic stroke mortality in multivariate Cox regression analysis (HR 4.776, p=0.032) (Figure 1). Conclusions: Multiple CMBs were the independent predictor for the long term mortality in stroke patients with NVAF. Among them, patients with strictly lobar CMBs had a high risk of death due to hemorrhagic stroke. Our findings suggest that detection of CMBs in stroke patients with NVAF are of clinical relevance for predicting long term outcome and that particular concern is necessary in those with strictly lobar CMBs for their increased risk of death due to hemorrhagic stroke. Figure 1.

scholarly journals Enhancing Recovery after Stroke with Noradrenergic Pharmacotherapy: A New Frontier?

2000 ◽  
Vol 27 (2) ◽  
pp. 97-105 ◽  
Author(s):  
David J. Gladstone ◽  
Sandra E. Black
Keyword(s):  
Animal Studies ◽  
Recovery Of Function ◽  
Recovery Process ◽  
Stroke Recovery ◽  
Therapeutic Interventions ◽  
New Frontier ◽  
Focal Brain Injury ◽  
Completed Stroke ◽  
Scientific Attention ◽  
Irreversible Injury

ABSTRACT:Despite much progress in stroke prevention and acute intervention, recovery and rehabilitation have traditionally received relatively little scientific attention. There is now increasing interest in the development of stroke recovery drugs and innovative rehabilitation techniques to promote functional recovery after completed stroke. Experimental work over the past two decades indicates that pharmacologic intervention to enhance recovery may be possible in the subacute stage, days to weeks poststroke, after irreversible injury has occurred. This paper discusses the concept of “rehabilitation pharmacology” and reviews the growing literature from animal studies and pilot clinical trials on noradrenergic pharmacotherapy, a new experimental strategy in stroke rehabilitation. Amphetamine, a monoamine agonist that increases brain norepinephrine levels, is the most extensively studied drug shown to promote recovery of function in animal models of focal brain injury. Further research is needed to investigate the mechanisms and clinical efficacy of amphetamine and other novel therapeutic interventions on the recovery process.

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