Risk of Stroke vs. Intracerebral Hemorrhage in Patients with Non-Valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing Dual vs. Triple Antithrombotic Therapy.

BACKGROUND: About 15% of patients with non-valvular atrial fibrillation might require percutaneous coronary interventions (PCIs) with stent placement to treat obstructive coronary artery disease. Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (aspirin) and P2Y12 antagonist is recommended after PCI. Patients requiring DAPT also require treatment with oral anticoagulation for atrial fibrillation. We conducted a meta-analysis to identify the antithrombotic regimen associated with the lowest rate of bleeding and thromboembolic events in non-valvular atrial fibrillation after PCI. METHODS: We searched PubMed, Embase, Scopus and Cochrane databases to identify randomized trials that investigated the use of dual antiplatelet therapy and vitamin K antagonist and/or Non-vitamin K antagonist oral anticoagulants (NOAC) (triple antithrombotic therapy (TAT)) against single antiplatelet agent and NOAC (dual antithrombotic therapy (DAT)) in the setting of coronary artery disease (CAD) requiring PCI and non-valvular atrial fibrillation. Random-effect models were used to pool data. We used the I2 statistic to measure heterogeneity between trials. RESULTS: We found 4 randomized clinical trials (ENTRUST, AUGUSTUS, PIONEER, REDUAL) using different NOACs. Overall, 9241 patients (median age 70 years, 41.4% female, mean CHADS2VASC Score 3.5) were included. We excluded patients in the very low dose rivaroxaban group from the PIONEER AF-PCI trial and low dose dabigatran group from the REDUAL PCI trial as these are not available in the United States. Our metanalysis showed that dual therapy was associated with less risk of intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.99; p = 0.045; I2 = 42%) and major bleeding (RR 0.66; 95% CI 0.55-0.79; p < 0.0001; I2 = 27%) as compared to triple therapy. Further risk of ischemic stroke (RR 0.94, 95% CI 0.63-1.39; p = 0.75; I2=0%), myocardial infarction (RR 1.18, 95% CI 0.94-1.47; p = 0.16; I2 = 0), or stent thrombosis (RR 0.50, 95% CI 0.93-2.41; p = 0.10; I2 = 0%) were unchanged. Similar findings were also noted on analysis of NOAC specific DAT vs VKA based TAT. CONCLUSIONS: The combination of an antiplatelet and NOACs (dual therapy) is associated with less risk of major bleeding and intracranial hemorrhage, with no significant difference in ischemic events (stroke myocardial infarction or stent thrombosis).

Nicardipine Associated Risk of Short-Term Mortality in Critically Ill Patients with Ischemic Stroke.

BACKGROUND: Hypertensive emergency is commonly associated with acute ischemic stroke and can be a predictor of poor outcome in these patients. Nicardipine and labetalol are commonly administered for the treatment of acute hypertension following stroke. Yet, data are lacking on the safety of these agents in this setting. OBJECTIVE: This study aimed to determine all-cause in-hospital mortality, medication-related hypotensive episodes, development of hospital acquired infections and hospital length of stay between nicardipine and labetalol use for the management of hypertension after acute ischemic stroke. METHODS: This retrospective study used a prospective database of individuals admitted to the neurointensive care unit at a university-based hospital over 39 months. Patients with confirmed ischemic strokes were included in this analysis. Data were recorded for administration of nicardipine and labetalol following acute stroke. RESULTS: A total of 244 patients with acute ischemic stroke were included in this analysis (mean age, 64.3 ± 15 years; 52.2% males). Nicardipine use after acute ischemic stroke was associated with an increased risk of 30-day mortality (odds ratio [OR]: 4.6, 95% confidence interval [CI] 1.3-15.7; P = .02). A single episode of hypotension in the first 72hours of admission was also significantly associated with mortality (OR 4.35 [95% CI 1.2-14.9]; P = .02). CONCLUSIONS: Nicardipine was associated with an increased risk of short-term mortality after acute ischemic stroke. This may have been due to hypotension, tachycardia, or pulmonary edema which were not apparent in our study. Further studies are required to elucidate the cause of this association.

Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

OBJECTIVES: Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH). PATIENTS AND METHODS: We searched PubMed and Embase databases to identify 1) prospective randomized trials, and 2) retrospective trials, between May 2009 and May 2017, that investigated the effect of cilostazol in patients with aneurysmal aSAH. All patients were enrolled after repair of a ruptured aneurysm by clipping or endovascular coiling within 72hours of aSAH. fixed-effect models were used to pool data. We used the I2 statistic to measure heterogeneity between trials. RESULTS: Five studies were included in our meta-analysis, comprised of 543 patients with aSAH (cilostazol [n=271]; placebo [n=272], mean age, 61.5years [SD, 13.1]; women, 64.0%). Overall, cilostazol was associated with a decreased risk of symptomatic vasospasm (0.31, 95% CI 0.20 to 0.48; P<0.001), cerebral infarction (0.32, 95% CI 0.20 to 0.52; P <0.001) and poor outcome (0.40, 95% CI 0.25 to 0.62; P<0.001). We observed no evidence for publication bias. Statistical heterogeneity was not present in any analysis. CONCLUSION: Cilostazol is associated with a decreased risk of symptomatic vasospasm and may be clinically useful in the treatment of delayed cerebral vasospasm in patients with aSAH. Our results highlight the need for a large multi-center trial to confirm the observed association.

Hyperosmolar therapy: A century of treating cerebral edema.

Hyperosmolar therapy is a cornerstone for the management of elevated intracranial pressure in patients with devastating neurological injuries. Its discovery and use in various pathologies has become a valuable therapy in modern neurological critical care across the globe. Although hyperosmolar therapy is used routinely, the history of its origin is still elusive to many physicians. Understanding the basis of discovery and use of different hyperosmolar agents lends insight into the complex management of elevated intracranial pressure. There are very few practices in medicine which has stood the test of time. The discovery of hyperosmolar therapy has not only provided us a wealth of data for the management of intracranial hypertension but has also allowed us to develop new treatment strategies by improving our understanding of the molecular mechanisms of cerebral inflammation, blood-brain permeability, and cerebral edema in all modes of neuronal injury.

Impact of systemic inflammatory response syndrome on acute ischemic stroke patients treated with mechanical thrombectomy.

AIM: Systemic inflammatory response syndrome (SIRS) has been associated with poor outcomes after acute ischemic stroke (AIS). The primary goal of this study was to determine whether SIRS status on admission correlated with functional outcomes in AIS treated with mechanical thrombectomy (MT). METHODS: Consecutive patients from September 2015 to April 2019 were retrospectively reviewed for SIRS on admission. SIRS was defined as the presence of ≥2 of the following: temperature < 36 °C or > 38 °C, heart rate > 90, respiratory rate > 20, and white blood cell count <4000/mm or > 12,000 mm. RESULTS: Of 202 patients, 188 met inclusion criteria. 49 patients (26%) had evidence of SIRS. Neither basic patient demographics nor standard stroke risk factors predicted the development of SIRS. However, presentation with SIRS was correlated with higher rates of death (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2-5.5) as well as lower rates of favorable functional outcomes at discharge (OR, 0.09; 95% CI, 0.02-0.40) and 3-month follow up (OR 0.12; 95% CI 0.03-0.43). These results remained significant even after adjustment for age, sex, baseline NIHSS, recanalization status, and prior co-morbidities. CONCLUSION: In our sample population, SIRS was associated with worse outcomes and higher rates of mortality in AIS patients treated with MT. Recognition of key risk factors can provide better prognostication and possible future therapeutic targets.

Blood pressure management after mechanical thrombectomy in stroke patients.

Endovascular treatment of acute ischemic stroke (AIS) and mechanical thrombectomy (MT) is proven as a safe and effective novel treatment for emergent large vessel occlusion in the anterior cerebral circulation. However, there are still many unanswered questions on peri and post-procedural management including blood pressure (BP) control. The current guidelines recommend maintaining BP <180/105 mmHg in the first 24 h after MT. However, recent studies suggest that maintaining BP levels at lower levels in the first 24 h after successful revascularization have been associated with favorable functional outcome, reduced mortality rate, and hemorrhagic complications. Not only absolute BP but also its variation in the first 24 h after MT have been associated with neurological outcomes. Evidence on the effect of BP variability (BPV) after MT in AIS even though limited, it does indicate the association of the higher BPV in the first 24 h after MT and poor functional outcomes in AIS. In this review, we will discuss the current literature on BP management in the first 24 h after MT and the impact of BPV in the first 24 h after MT.

Gabapentin or pregabalin induced myoclonus: A case series and literature review.

Gabapentin (GBP) and pregabalin (PGB) are FDA approved for adjunctive treatment of partial seizures and for treatment of post-herpetic neuralgia. Both drugs are primarily eliminated by renal excretion. However, PGB or GBP induced myoclonus has only been reported infrequently in case reports/series. It is not discussed with patients and its sudden occurrence can lead to anxiety because of "seizure-like" nature. In addition, first-contact physicians might treat it as seizures, leading to unnecessary tests and aggressive management. Medical records of patients who had myoclonus because of PGB or GBP seen by Neurology service between Jan & May 2017 in inpatient or outpatient setting at our tertiary care setting were reviewed. We identified six patients who were on either GBP or PGB or both who developed likely subcortical myoclonus in the setting of renal insufficiency and one patient who developed myoclonus independent of renal dysfunction. Our results indicate that myoclonus is commonly seen in patients in various clinical settings with or without renal insufficiency, and is independent of the severity of the renal failure. However, this is a reversible side effect of medication and it resolves either by discontinuing the medication, removing the medication with hemodialysis or by improvement of renal dysfunction. With a high index of suspicion, aggressive testing and treatment for other possible conditions like seizures (in non-epilepsy patients) or CNS infections can be avoided. In patients with renal failure and with decreased physiological renal clearance such as the elderly, GBP or PGB dose initiation and changes should be conservative.

Updates in Refractory Status Epilepticus.

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status.