Archit Bhatt

Sex Differences in the Use of Intravenous rt-PA Thrombolysis Treatment for Acute Ischemic Stroke A Meta-Analysis

BACKGROUND AND PURPOSE Some studies report that women are less likely to receive IV rt-PA treatment for stroke than men. We undertook a meta-analysis to determine whether a sex disparity existed. METHODS We identified studies that reported sex-specific IV rt-PA treatment rates for acute stroke. Eligible studies included acute stroke admissions from single or multiple hospitals, registries, or administrative databases. Random effects odds ratios (OR) and 95% confidence intervals (CI) were generated to quantify sex differences (females versus males) among all ischemic stroke admissions and among the eligible subgroup who arrived within 3 hours without contraindications. Study design and geographic location were explored as sources of heterogeneity. RESULTS Eighteen studies were included. Study designs included single hospitals (n=5), multiple hospitals (n=6), registries (n=4), and administrative databases (n=3). The summary OR was 0.70 (95% CI=0.55 to 0.88) indicating that women had a 30% lower odds of receiving rt-PA treatment than men. However, substantial between-study variability existed. Among 13 hospital-based studies, the summary OR was 0.78 (95% CI=0.71 to 0.86) with no significant heterogeneity. Among the 3 administrative studies, the OR was 0.55 (95% CI=0.34 to 0.90) but with significant heterogeneity. Among 4 studies that included data on the eligible subgroup, women had a nonsignificant lower odds of treatment (OR=0.81, 95% CI=0.58 to 1.13). CONCLUSIONS Despite the presence of significant between-study variation, women with acute stroke were consistently less likely to receive thrombolysis treatment compared with men. Further studies to explore the origins of this sex disparity are warranted.

Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia

The present study sought to determine the neuroprotective effect of anthocyanin cyanidin-3-O-glucoside (CG), isolated and purified from tart cherries, against permanent middle cerebral artery occlusion (pMCAO) in mice and its potential mechanisms of neuroprotection. C57BL/6 mice subjected to pMCAO were treated with CG orally. Twenty-four hours after pMCAO, neurological scoring was used to evaluate functional outcome. The brains were then excised for measuring infarct volume and brain superoxide levels were determined. In a separate set of experiments, the influence of CG on cytochrome c (cyt c) and apoptosis-inducing factor (AIF) release from mitochondria under oxidative stress were assessed in isolated cortical neurons from adult mouse brains. Infarction volume was attenuated by 27% in mice pre-treated with 2mg/kg of CG compared to vehicle-treated mice. Delayed treatment with 2mg/kg of CG also showed 25% reduction in infarct size. Neurological functional outcome was significantly improved in mice pre- or post-treated with CG. Compared to vehicle treated mice CG treated mice had lower levels of brain superoxide. CG also blocked the release of AIF from mitochondria under oxidative stress, but did not inhibit the release of cyt c. Our data show that CG is neuroprotective against pMCAO in mice, and this beneficial effect may be mediated by attenuation of brain superoxide levels after ischemia. CG may also exert its neuroprotective effect by blocking AIF release in mitochondria.

Predictors of Occult Paroxysmal Atrial Fibrillation in Cryptogenic Strokes Detected by Long-Term Noninvasive Cardiac Monitoring

Background and Purpose. Paroxysmal Atrial fibrillation/Flutter (PAF) detection rates in cryptogenic strokes have been variable. We sought to determine the percentage of patients with cryptogenic stroke who had PAF on prolonged non-invasive cardiac monitoring. Methods and Results. Sixty-two consecutive patients with stroke and TIA in a single center with a mean age of 61 (+/− 14) years were analyzed. PAF was detected in 15 (24%) patients. Only one patient reported symptoms of shortness of breath during the episode of PAF while on monitoring, and 71 (97%) of these 73 episodes were asymptomatic. A regression analysis revealed that the presence of PVCs (ventricular premature beats) lasting more than 2 minutes (OR 6.3, 95% CI, 1.11–18.92; P = .042) and strokes (high signal on Diffusion Weighted Imaging) (OR 4.3, 95% CI, 5–36.3; P = .041) predicted PAF. Patients with multiple DWI signals were more likely than solitary signals to have PAF (OR 11.1, 95% CI, 2.5–48.5, P < .01). Conclusion. Occult PAF is common in cryptogenic strokes, and is often asymptomatic. Our data suggests that up to one in five patients with suspected cryptogenic strokes and TIAs have PAF, especially if they have PVCs and multiple high DWI signals on MRI.

Anesthesia for endovascular treatment of acute ischemic stroke

The initial treatment of patients with acute ischemic stroke (AIS) focuses on rapid recanalization, which often includes the use of endovascular therapies. Endovascular treatment depends upon micronavigation of catheters and devices into the cerebral vasculature, which is easier and safer with a motionless patient. Unfortunately, many stroke patients are unable to communicate and sufficiently cooperate with the procedure. Thus, general anesthesia (GA) with endotracheal intubation provides an attractive means of keeping the patient comfortable and motionless during a procedure that could otherwise be lengthy and uncomfortable. However, several recent retrospective studies have shown an association between GA and poorer outcomes in comparison with conscious sedation for endovascular treatment of AIS, though prospective studies are lacking. The underlying reasons why GA might produce a worse outcome are unknown but may include hemodynamic instability and hypotension, delays in treatment, prolonged intubation with or without neuromuscular blockade, or even neurotoxicity of the anesthetic agent itself. Currently, the choice between GA and conscious sedation should be tailored to the individual patient, on the basis of neurologic deficits, airway and hemodynamic status, and treatment plan. The use of institutional treatment protocols may best support efficient and effective care for AIS patients undergoing endovascular therapy. Important components of such protocols would include parameters to choose anesthetic modality, timeliness of induction, blood pressure goals, minimization of neuromuscular blockade, and planned extubation at the end of the procedure.

Cardiac Dysfunction After Left Permanent Cerebral Focal Ischemia The Brain and Heart Connection

Background and Purpose— Stroke can lead to cerebrogenic cardiac arrhythmias. We sought to investigate the effect of ischemic stroke on cardiac function in a mouse model of permanent middle cerebral artery occlusion (pMCAO). Methods— Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined. Results— Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction. Conclusions— This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart.

Levetiracetam for managing neurologic and psychiatric disorders

PURPOSE The role of levetiracetam in different epileptic, nonepileptic, neurologic, and psychiatric disorders is discussed. SUMMARY Levetiracetam, an antiepileptic drug (AED), was first approved as an adjunctive therapy for the treatment of partial epilepsy in adults. It is currently being used in the treatment of multiple seizure disorders, including generalized tonic-clonic; absence; myoclonic, especially juvenile myoclonic; Lennox-Gastaut syndrome; and refractory epilepsy in children and adults. Data are emerging on possible uses of levetiracetam outside the realm of epilepsy because of its unique mechanisms of action. There is preliminary evidence about the efficacy of levetiracetam in the treatment of different psychiatric disorders, including anxiety, panic, stress, mood and bipolar, autism, and Tourettes syndrome. The most serious adverse effects associated with levetiracetam use are behavioral in nature and might be more common in patients with a history of psychiatric and neurobehavioral problems. CONCLUSION Levetiracetam is an effective AED with potential benefits in other neurologic and psychiatric disorders. The benefit-risk ratio in an individual patient with a specific condition should be used to determine its optimal use. Levetiracetams use in nonepileptic conditions is not recommended until more data become available from larger trials.

Safety and Efficacy Evaluation of Carnosine, an Endogenous Neuroprotective Agent for Ischemic Stroke

Background and Purpose— An urgent need exists to develop therapies for stroke that have high efficacy, long therapeutic time windows, and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. Methods— Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. Results— Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically relevant therapeutic time windows of 6 hours and 9 hours in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained on 14th day poststroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests, and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust antiexcitotoxic, antioxidant, and mitochondria protecting activity. Conclusions— In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

Chemotherapy-related posterior reversible leukoencephalopathy syndrome.

Background A 45-year-old woman with small-cell lung cancer presented to a hospital emergency department in an acute confusional state, with blurred vision and mild headache. Following progressively increasing lethargy, she subsequently became unresponsive to tactile and verbal stimuli. She had recently been started on chemotherapy with carboplatin and gemcitabine.Investigations Physical examination, imaging studies including brain MRI, noncontrast brain CT scans and magnetic resonance angiography, continuous EEG monitoring, and cerebrospinal fluid analysis.Diagnosis Posterior reversible leukoencephalopathy syndrome (PRES) related to chemotherapy, and nonconvulsive status epilepticus related to PRES.Management Withholding of chemotherapeutic agents, and antiseizure therapy for the status epilepticus.

Neurotoxic and Cardiotoxic Effects of Cocaine and Ethanol

IntroductionConcurrent abuse of alcohol and cocaine results in the formation of cocaethylene, a powerful cocaine metabolite. Cocaethylene potentiates the direct cardiotoxic and indirect neurotoxic effects of cocaine or alcohol alone.Case ReportA 44-year-old female with history of cocaine and alcohol abuse presented with massive stroke in the emergency department. CT scan revealed extensive left internal carotid artery dissection extending into the left middle and anterior cerebral arteries resulting in a massive left hemispheric infarct, requiring urgent decompressive craniectomy. The patient had a stormy hospital course with multiple episodes of torsades de pointes in the first 4 days requiring aggressive management. She survived all events and was discharged to a nursing home with residual right hemiplegia and aphasia.ConclusionThe combination of ethanol and cocaine has been associated with a significant increase in the incidence of neurological and cardiac emergencies including cerebral infarction, intracranial hemorrhage, myocardial infarction, cardiomyopathy, and cardiac arrhythmias. The alteration of cocaine pharmacokinetics and the formation of cocaethylene have been implicated, at least partially, in the increased toxicity of this drug combination.

Medicolegal Considerations with Intravenous Tissue Plasminogen Activator in Stroke: A Systematic Review

Background. Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that physicians are increasingly liable for administering and for failure to administer tPA. Methods. An extensive search of Medline, Embase, Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case studies that involved malpractice litigation in ischemic stroke and thrombolytic therapy were analyzed systematically. Results. We identified 789 ischemic stroke litigation cases, of which 46 cases were related to intravenous tPA and stroke litigation. Case descriptions of 40 cases were available. Data for verdicts were available for 38 patients. The most frequent plaintiff claim was related to failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved complications of treatment with tPA. Hospitals were defendants in majority of the 36 cases. Physicians were involved in 33 cases. While ED physicians were involved in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were 26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts. Conclusion. Physicians and hospitals are at an increased risk of litigation in patients with AIS when in IV-tPA is being considered for treatment. While majority of the cases litigated were cases where tPA was not administered, only about 1 in 20 cases was litigated when complications occurred.