Cardiomyopathy in Patients With Acute Ischemic Stroke and Methamphetamine Use: Relevance for Cardioembolic Stroke and Outcome.

BACKGROUND: Methamphetamine use has emerged as a major risk factor for cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate a possible association of methamphetamine use with cardioembolic stroke. METHODS AND RESULTS: We performed a retrospective study of patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy, defined as left ventricular ejection fraction ≤45%. Among 938 consecutive patients, 46 (4.9%) were identified as using methamphetamine. Compared with the nonmethamphetamine group (n=892), the methamphetamine group was significantly younger (52.8±9.6 versus 69.7±15.2 years; P<0.001), included more men (78.3% versus 52.8%; P<0.001), and had a significantly higher rate of cardiomyopathy (30.4% versus 14.0%; P<0.01). They were also less likely to have a history of atrial fibrillation (8.7% versus 33.4%; P<0.01) or hyperlipidemia (28.3% versus 51.7%; P<0.01). Compared with patients with cardiomyopathy without methamphetamine use, the patients with cardiomyopathy with methamphetamine use had significantly lower left ventricular ejection fraction (26.0±9.59% versus 32.47±9.52%; P<0.01) but better functional outcome at 3 months, likely attributable to significantly younger age and fewer comorbidities. In the logistic regression model of clinical variables, methamphetamine-associated cardiomyopathy was found to be significantly associated with cardioembolic stroke (odds ratio, 1.79 [95% CI, 1.04-3.06]; P<0.05). CONCLUSIONS: We demonstrate that methamphetamine use is significantly associated with cardiomyopathy and cardioembolic stroke in young adults.

Rescue therapy after thrombectomy for large vessel occlusion due to underlying atherosclerosis: review of literature.

In this review article, we summarized the current advances in rescue management for reperfusion therapy of acute ischemic stroke from large vessel occlusion due to underlying intracranial atherosclerotic stenosis (ICAS). It is estimated that 24-47% of patients with acute vertebrobasilar artery occlusion have underlying ICAS and superimposed in situ thrombosis. These patients have been found to have longer procedure times, lower recanalization rates, higher rates of reocclusion and lower rates of favorable outcomes than patients with embolic occlusion. Here, we discuss the most recent literature regarding the use of glycoprotein IIb/IIIa inhibitors, angioplasty alone, or angioplasty with stenting for rescue therapy in the setting of failed recanalization or instant/imminent reocclusion during thrombectomy. We also present a case of rescue therapy post intravenous tPA and thrombectomy with intra-arterial tirofiban and balloon angioplasty followed by oral dual antiplatelet therapy in a patient with dominant vertebral artery occlusion due to ICAS. Based on the available literature data, we conclude that glycoprotein IIb/IIIa is a reasonably safe and effective rescue therapy for patients who have had a failed thrombectomy or have residual severe intracranial stenosis. Balloon angioplasty and/or stenting may be helpful as a rescue treatment for patients who have had a failed thrombectomy or are at risk of reocclusion. The effectiveness of immediate stenting for residual stenosis after successful thrombectomy is still uncertain. Rescue therapy does not appear to increase the risk of sICH. Randomized controlled trials are warranted to prove the efficacy of rescue therapy.

Methamphetamine use increases the risk of cerebral small vessel disease in young patients with acute ischemic stroke.

Methamphetamine use causes spikes in blood pressure. Chronic hypertension is a major risk factor for cerebral small vessel disease (cSVD). The aim of this study is to investigate whether methamphetamine use increases the risk of cSVD. Consecutive patients with acute ischemic stroke at our medical center were screened for methamphetamine use and evidence of cSVD on MRI of the brain. Methamphetamine use was identified by self-reported history and/or positive urine drug screen. Propensity score matching was used to select non-methamphetamine controls. Sensitivity analysis was performed to assess the effect of methamphetamine use on cSVD. Among 1369 eligible patients, 61 (4.5%) were identified to have a history of methamphetamine use and/or positive urine drug screen. Compared with the non-methamphetamine group (n = 1306), the patients with methamphetamine abuse were significantly younger (54.5 ± 9.7 vs. 70.5 ± 12.4, p < 0.001), male (78.7% vs. 54.0%, p < 0.001) and White (78.7% vs. 50.4%, p < 0.001). Sensitivity analysis showed that methamphetamine use was associated with increased white matter hyperintensities, lacunes, and total burden of cSVD. The association was independent of age, sex, concomitant cocaine use, hyperlipidemia, acute hypertension, and stroke severity. Our findings suggest that methamphetamine use increases the risk of cSVD in young patients with acute ischemic stroke.

Intracranial Arterial Calcifications: Potential Biomarkers of Stroke Risk and Outcome.

Intracranial artery calcifications (IAC), a common and easily identifiable finding on computed tomorgraphy angiography (CTA), has gained recognition as a possible risk factor for ischemic stroke. While atherosclerosis of intracranial arteries is believed to be a mechanism that commonly contributes to ischemic stroke, and coronary artery calcification is well-established as a predictor of both myocardial infarction (MI) and ischemic stroke risk, IAC is not currently used as a prognostic tool for stroke risk or recurrence. This review examines the pathophysiology and prevalence of IAC, and current evidence suggesting that IAC may be a useful tool for prediction of stroke incidence, recurrence, and response to acute ischemic stroke therapy.

Comparative Studies of Cerebral Reperfusion Injury in the Posterior and Anterior Circulations After Mechanical Thrombectomy.

Cerebral reperfusion injury is the major complication of mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Contrast extravasation (CE) and intracranial hemorrhage (ICH) are the key radiographical features of cerebral reperfusion injury. The aim of this study was to investigate CE and ICH after MT in the anterior and posterior circulation, and their effect on functional outcome. This is a retrospective study of all consecutive patients who were treated with MT for AIS at University of California Irvine Medical Center between January 1, 2014, and December 31, 2017. Patient characteristics, clinical features, procedural variables, contrast extravasation, ICH, and outcomes after MT were analyzed. A total of 131 patients with anterior circulation (AC) stroke and 25 patients with posterior circulation (PC) stroke underwent MT during the study period. There was no statistically significant difference in admission NIHSS score, blood pressure, rate of receiving intravenous tPA, procedural variables, contrast extravasation, and symptomatic ICH between the 2 groups. Patients with PC stroke had a similar rate of favorable outcome (mRS 0-2) but significantly higher mortality (40.0% vs. 10.7%, p < 0.01) than patients with AC stroke. Multivariate regression analysis identified initial NIHSS score (OR 1.1, CI 1.0-1.2, p = 0.01), number of passes with stent retriever (OR 2.1, CI 1.3-3.6, p < 0.01), and PC stroke (OR 9.3, CI 2.5-35.1, p < 0.01) as independent risk factors for death. There was no significant difference in functional outcomes between patients with and without evidence of cerebral reperfusion injury after MT. We demonstrated that AC and PC stroke had similar rates of cerebral reperfusion injury and favorable outcome after MT. Cerebral reperfusion injury is not a significant independent risk factor for poor functional outcome.

Control of single and multiple phase solitons in a ring cavity.

Phase solitons are localized structures characterized by phase jumps of 2π or multiples arising in forced ring lasers. Here, we show numerically that they can be created by superimposing to the constant driving field a suitable control beam matched in frequency with a different cavity mode for a time of the order of ten cavity round trip times. If the two beams are separated in frequency by n free spectral ranges of the cavity, a train of solitons like a perfect soliton crystal consisting of n equispaced phase solitons is generated. This may represent a simple way to produce frequency combs with flexible frequency spacing and high power per line.

Left Atrial Dilatation and Reduced Left Ventricular Ejection Fraction Are Associated With Cardioembolic Stroke.

Objective: Left atrial (LA) dilatation and heart failure are independent risk factors for ischemic stroke. The goal of this study is to evaluate the association between LA dilatation and reduced left ventricular ejection fraction (EF) with cardioembolic stroke. Methods: Four hundred fifty-three patients with ischemic stroke admitted to the University of California, Irvine between 2016 and 2017 were included based on the following criteria: age >18 and availability of echocardiogram. Stroke was categorized into cardioembolic and non-cardioembolic. EF was categorized into normal: 52-72% (male), 54-74% (female), mildly abnormal: 41-51% (male), 41-53% (female), moderately abnormal: 30-40%, and severely abnormal: <30%. LA volume was categorized into normal (≤34 ml/m2) vs. enlarged (≥35 ml/m2). Other variables included gender, hypertension [systolic blood pressure (SBP) ≥ 140 or diastolic blood pressure (DBP) ≥ 90], and known history of atrial fibrillation (Afib). Results: Two hundred eighteen patients had cardioembolic, and 235 had non-cardioembolic stroke. Among patients with cardioembolic stroke, 49 (22.4%) and 142 (65%) had reduced EF and enlarged LA, respectively, as compared with 19 (8.1%) and 65 (27.7%) patients with non-cardioembolic stroke (p < 0.0001). The odds of cardioembolic stroke were 2.0 (95% CI: 0.1-6.0) and 8.8 times (95% CI: 1.9-42.3) higher in patients with moderately and severely reduced EF, respectively, than in patients with normal EF. The odds of cardioembolic stroke was 2.4 times (95% CI: 1.5-3.9) higher in patients with enlarged LA than in patients with normal LA size. Compared with patients with normal LA and EF, patients with combined enlarged LA and reduced EF had significantly higher rates of Afib (43.4 vs. 9.0%, p < 0.0001) and cardioembolic stroke (78.3 vs. 43.4%, p < 0.0001). Conclusions: LA dilatation along with reduced EF is a reliable predictor of Afib and cardioembolic stroke. Further studies are warranted to determine the benefit of anticoagulation for secondary stroke prevention in such patient population.

Recanalization Therapy for Acute Ischemic Stroke with Large Vessel Occlusion: Where We Are and What Comes Next?

In the past 5 years, the success of multiple randomized controlled trials of recanalization therapy with endovascular thrombectomy has transformed the treatment of acute ischemic stroke with large vessel occlusion. The evidence from these trials has now established endovascular thrombectomy as standard of care. This review will discuss the chronological evolution of large vessel occlusion treatment from early medical therapy with tissue plasminogen activator to the latest mechanical thrombectomy. Additionally, it will highlight the potential areas in endovascular thrombectomy for acute ischemic stroke open to exploration and further progress in the next decade.

Coagulopathy reversal in intracerebral haemorrhage.

As intracerebral hemorrahge becomes more frequent as a result of an aging population with greater comorbidities, rapid identification and reversal of precipitators becomes increasingly paramount. The aformentioned population will ever more likely be on some form of anticoagulant therapy. Understanding the mechanisms of these agents and means by which to reverse them early on is critical in managing the acute intracerebral hemorrhage.

Clinical characteristics and outcomes of methamphetamine-associated versus non-methamphetamine intracerebral hemorrhage.

Methamphetamine use has emerged as a risk factor for intracerebral hemorrhage (ICH). We aim to investigate the clinical characteristics and outcomes of methamphetamine-associated ICH (Meth-ICH) versus Non-Meth-ICH. Patients with ICH between January 2011 and December 2017 were studied. Meth-ICH and Non-Meth-ICH were defined by history of abuse and urine drug screen (UDS). The clinical features of the 2 groups were explored. Among the 677 consecutive patients, 61 (9.0%) were identified as Meth-ICH and 350 as Non-Meth ICH. Meth-ICH was more common in Hispanics (14.6%) and Whites (10.1%) as compared to Asians (1.2%). Patients with Meth-ICH were more often younger (51.2 vs. 62.2 years, p < 0.001), male (77.0% vs. 61.4.0%, p < 0.05), and smokers (44.3% vs. 13.4%, p < 0.001). Non-Meth-ICH was more likely to have history of hypertension (72.61% v. 59%, p < 0.05) or antithrombotic use (10.9% vs. 1.6%, p < 0.05). There was no significant difference in clinical severity, hospital length of stay (LOS), rate of functional independence (29.5% vs. 25.7%, p = 0.534), or mortality (18.0% vs. 24.6%, p = 0.267) between the 2 groups. Methamphetamine use was not an independent predictor of poor outcome. Despite difference in demographics, Meth-ICH is similar to Non-Meth ICH in hospital course and outcome.

Three easily-implementable changes reduce median door-to-needle time for intravenous thrombolysis by 23 minutes.

BACKGROUND: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke is time dependent. Despite great effort, the median door-to-needle time (DNT) was 60 min at the United States stroke centers. We investigated the effect of a simple quality improvement initiative on DNT for IVT. METHODS: This is a single-center study of patients treated with IVT between 2013 and 2017. A simple quality improvement initiative was implemented in January 2015 to allow the Stroke team to manage hypertension in the emergency room, to make decision for IVT before getting blood test results unless patients were taking oral anticoagulants, and to give IVT in the CT suite. Baseline characteristics, DNT and outcomes at hospital discharge were compared between pre- and post-intervention groups. RESULTS: Ninety and 136 patients were treated with IVT in pre- and post-intervention groups, respectively. The rate of IVT was significantly higher in the post-intervention group (20% vs. 14.4%, p = 0.007). The median DNT with interquartile range (IQR) was reduced significantly by 23 min (63[53-81] vs. 40[29-53], p < 0.001) with more patients in the post-intervention group receiving IVT within 60 min (81.6% vs. 46.7%) and 45 min (64.0% vs.17.8%). There was no significant difference in symptomatic intracerebral hemorrhage rate (1.5% vs. 1.1%), modified Rankin Scale 0-1 (29.4% vs. 23.3%), and hospital mortality (7.4% vs. 6.7%) between the 2 groups. CONCLUSIONS: Three easily-implementable quality improvement initiative increases IVT rate and reduces DNT significantly without increasing the rate of IVT-related complications in our comprehensive stroke center.

Erythrocyte-Derived Nanoparticles as a Theranostic Agent for Near-Infrared Fluorescence Imaging and Thrombolysis of Blood Clots.

Ischemic stroke occurs when a blood clot obstructs or narrows the arteries that supply blood to the brain. Currently, tissue plasminogen activator (tPA), a thrombolytic agent, is the only United States Food and Drug Administration (FDA)-approved pharmacologic treatment for ischemic stroke. Despite its effective usage, the major limitation of tPA that stems from its short half-life in plasma (≈5 min) is the potential for increased risk of hemorrhagic complications. To circumvent these limitations, herein, the first proof-of-principle demonstration of a theranostic nanoconstruct system derived from erythrocytes doped with the FDA-approved near-infrared (NIR) imaging agent, indocyanine green, and surface-functionalized with tPA is reported. Using a clot model, the dual functionality of these nanoconstructs in NIR fluorescence imaging and clot lysis is demonstrated. These biomimetic theranostic nanoconstructs may ultimately be effective in imaging and treatment of blood clots involved in ischemic stroke.

Recurrent Attacks of Hypokalemic Quadriparesis: An Unusual Presentation of Primary Sjögren Syndrome.

We herein report the case of a 64-year old woman with recurrent attacks of hypokalemic quadriparesis which resulted from distal renal tubular acidosis (dRTA) secondary to Sjögren syndrome. The patient presented with sudden onset quadriparesis. A physical examination showed symmetric weakness of all four limbs. Severe hypokalemia (1.8 mEq/L), accompanied by normal anion gap metabolic acidosis, a positive urine anion gap and an inappropriately high urine pH pointed toward the diagnosis of dRTA. Further investigations disclosed primary Sjögren syndrome, which had not previously been recognized. On the basis of the current report and a review of the literature we suggest investigating the possibility of Sjögren syndrome in all patients with clinically unexplained dRTA.