Shadi Yaghi

Left Atrial Enlargement and Stroke Recurrence The Northern Manhattan Stroke Study

Background and Purpose— Although left atrial enlargement (LAE) increases incident stroke risk, the association with recurrent stroke is less clear. Our aim was to determine the association of LAE with recurrent stroke most likely related to embolism (cryptogenic and cardioembolic) and all ischemic stroke recurrences. Methods— We followed 655 first ischemic stroke patients in the Northern Manhattan Stroke Study for ⩽5 years. LA size from 2D echocardiography was categorized as normal LAE (52.7%), mild LAE (31.6%), and moderate–severe LAE (15.7%). We used Cox proportional hazard models to calculate the hazard ratios and 95% confidence intervals for the association of LA size and LAE with recurrent cryptogenic/cardioembolic and total recurrent ischemic stroke. Results— LA size was available in 529 (81%) patients. Mean age at enrollment was 69±13 years; 45.8% were male, 54.0% Hispanic, and 18.5% had atrial fibrillation. Over a median of 4 years, there were 65 recurrent ischemic strokes (29 were cardioembolic or cryptogenic). In multivariable models adjusted for confounders, including atrial fibrillation and heart failure, moderate–severe LAE compared with normal LA size was associated with greater risk of recurrent cardioembolic/cryptogenic stroke (adjusted hazard ratio 2.83, 95% confidence interval 1.03–7.81), but not total ischemic stroke (adjusted hazard ratio 1.06, 95% confidence interval, 0.48–2.30). Mild LAE was not associated with recurrent stroke. Conclusion— Moderate to severe LAE was an independent marker of recurrent cardioembolic or cryptogenic stroke in a multiethnic cohort of ischemic stroke patients. Further research is needed to determine whether anticoagulant use may reduce risk of recurrence in ischemic stroke patients with moderate to severe LAE.

Symptomatic Intracerebral Hemorrhage in Acute Ischemic Stroke After Thrombolysis With Intravenous Recombinant Tissue Plasminogen Activator: A Review of Natural History and Treatment

IMPORTANCEnIntravenous thrombolysis remains the mainstay treatment for acute ischemic stroke. One of the most feared complications of the treatment is thrombolysis-related symptomatic intracerebral hemorrhage (sICH), which occurs in nearly 6% of patients and carries close to 50% mortality. The treatment options for sICH are based on small case series and expert opinion, and the efficacy of recommended treatments is not well known.nnnOBJECTIVEnTo provide an overview on the rationale and mechanism of action of potential treatments for sICH that may reverse the coagulopathy before hematoma expansion occurs.nnnEVIDENCE REVIEWnEvidence-based peer-reviewed articles, including randomized trials, case series and reports, and retrospective reviews, were identified in a PubMed search on the mechanism of action of intravenous recombinant tissue plasminogen activator and the rationale of various potential treatments using the coagulation cascade as a model. The search encompassed articles published from January 1, 1990, through February 28, 2014.nnnFINDINGSnThe current treatments may not be sufficient to reverse coagulopathy early enough to prevent hematoma expansion and improve the outcome of thrombolysis-related hemorrhage.nnnCONCLUSIONS AND RELEVANCEnGiven the mechanism of action of intravenous recombinant tissue plasminogen activator, clinical studies could include agents with a fast onset of action, such as prothrombin complex concentrate, recombinant factor VIIa, and ε-aminocaproic acid, as potential therapeutic options.

Cryptogenic stroke A diagnostic challenge

Cryptogenic, or unexplained, stroke is present in about 30%-40% of ischemic stroke patients. Pursuing a stroke mechanism is important in such patients to better choose therapy to reduce the stroke recurrence risk. Intracranial vessel imaging and cardiac evaluation with transesophageal echocardiogram and outpatient cardiac monitoring may help identify the stroke mechanism. This article highlights the diagnostic yield of various tests in identifying a stroke mechanism in stroke patients whose initial diagnostic evaluation is negative, and the implications for treatment.

Electrocardiographic Left Atrial Abnormality and Risk of Stroke Northern Manhattan Study

Background and Purpose— Electrocardiographic left atrial abnormality has been associated with stroke independently of atrial fibrillation (AF), suggesting that atrial thromboembolism may occur in the absence of AF. If true, we would expect an association with cryptogenic or cardioembolic stroke rather than noncardioembolic stroke. Methods— We conducted a case-cohort analysis in the Northern Manhattan Study, a prospective cohort study of stroke risk factors. P-wave terminal force in lead V1 was manually measured from baseline ECGs of participants in sinus rhythm who subsequently had ischemic stroke (n=241) and a randomly selected subcohort without stroke (n=798). Weighted Cox proportional hazard models were used to examine the association between P-wave terminal force in lead V1 and stroke etiologic subtypes while adjusting for baseline demographic characteristics, history of AF, heart failure, diabetes mellitus, hypertension, tobacco use, and lipid levels. Results— Mean P-wave terminal force in lead V1 was 4452 (±3368) &mgr;V*ms among stroke cases and 3934 (±2541) &mgr;V*ms in the subcohort. P-wave terminal force in lead V1 was associated with ischemic stroke (adjusted hazard ratio per SD, 1.20; 95% confidence interval, 1.03–1.39) and the composite of cryptogenic or cardioembolic stroke (adjusted hazard ratio per SD, 1.31; 95% confidence interval, 1.08–1.58). There was no definite association with noncardioembolic stroke subtypes (adjusted hazard ratio per SD, 1.14; 95% confidence interval, 0.92–1.40). Results were similar after excluding participants with a history of AF at baseline or new AF during follow-up. Conclusions— ECG-defined left atrial abnormality was associated with incident cryptogenic or cardioembolic stroke independently of the presence of AF, suggesting atrial thromboembolism may occur without recognized AF.

Mechanisms and outcomes of stroke during pregnancy and the postpartum period: A cross-sectional study

Background:Pregnancy-associated stroke remains incompletely characterized because of the rarity of these potentially devastating events. We investigated whether mechanism and outcome of ischemic pathophysiology stroke differ between young pregnant and nonpregnant women. Methods:We identified 135 consecutive women ages 18–40 years admitted to our center from January 2008 through June 2014 with ischemic stroke, TIA, cerebral venous thrombosis, or nonaneurysmal subarachnoid hemorrhage due to reversible cerebral vasoconstriction syndrome (RCVS). We reviewed charts for pregnancy status, demographics, medical comorbidities, stroke severity, etiology, and discharge outcomes. Results:There were 33 women with pregnancy-associated stroke (PAS) and 102 with non–pregnancy-associated stroke (NPAS). Among women with PAS, 73% of strokes occurred postpartum. In the PAS group, the most common cause of cerebrovascular events was RCVS (n = 12), 11 postpartum and 4 in women with preeclampsia. There were no significant differences between the groups in demographics. Women with PAS were less likely to have vascular risk factors such as hyperlipidemia and history of thromboembolism but more likely to have cerebral venous thromboses (21% vs 7%, p = 0.02). Women with PAS were more likely to have RCVS as stroke mechanism (36% vs 1%, odds ratio 57.7, 95% confidence interval 7–468, p = 0.0001). Conclusion:Compared with nonpregnant women of the same age group, women with PAS had fewer vascular risk factors. Cerebral venous thrombosis and RCVS were more common in PAS, most of which occurred postpartum. These results provide further evidence for the unique pathophysiology of pregnancy-related stroke, raising important questions for future investigation.

The CHADS2 Components Are Associated with Stroke-Related In-hospital Mortality in Patients with Atrial Fibrillation.

BACKGROUNDnThe CHADS2 score predicts stroke risk in patients with atrial fibrillation. Although strokes caused by atrial fibrillation carry the highest mortality when compared with other etiologies, it is not known whether the CHADS2 score predicts stroke-related mortality in patients with atrial fibrillation. We hypothesized that higher CHADS2 scores would be associated with higher stroke-related in-hospital mortality.nnnMETHODSnData were obtained from administrative claims data from all emergency department encounters and hospitalizations at Californias nonfederal acute care hospitals between 2008 and 2011. Patients with atrial fibrillation and an admission for acute stroke were identified using appropriate International Classification of Diseases, Ninth Revision (ICD-9), Clinical Modification codes. Age and ICD-9 codes for hypertension, diabetes, congestive heart failure, and prior stroke were used to calculate the CHADS2 score of patients with atrial fibrillation. The primary outcome was in-hospital stroke mortality and the primary predictor was CHADS2 score. A multivariate logistic regression model adjusted for sex and race was used to determine the odds ratio (OR) and 95% confidence interval (CI) for the association between CHADS2 and mortality.nnnRESULTSnBetween January 1, 2008, and December 31, 2011, 25,599 patients with atrial fibrillation were hospitalized with a stroke. The odds of in-hospital mortality was significantly higher with a CHADS2 score of 2 more versus less than 2 (OR, 1.15; 95% CI, 1.08-1.23); however, there was no dose-response association between the CHADS2 score and in-hospital mortality. Among the individual CHADS2 score items, factors associated with increased in-hospital mortality were congestive heart failure (OR, 1.61; 95% CI, 1.53-1.70), age 75 years or older (OR, 1.27; 95% CI, 1.19-1.35), and diabetes (OR, 1.24; 95% CI, 1.14-1.35).nnnCONCLUSIONSnUnlike prior studies, our studies show that the prestroke CHADS2 score is of limited use in predicting in-hospital mortality in ischemic stroke hospitalizations in patients with atrial fibrillation.

Clinical Reasoning: An 87-year-old woman with left-sided numbness.

An 87-year-old woman with a history of hypertension, hyperlipidemia, and peripheral vascular disease presented with acute left paresthesias. On evaluation, blood pressure was 152/77 mm Hg and heart rate 78 and regular. Physical examination had normal results. On neurologic examination, she had normal mental status, decreased sensation on the left face, and normal strength, tone, and reflexes. Cerebellar examination and gait were normal. There was reduced light touch and pinprick sensation of the left arm and leg, with no extinction. Complete blood count and comprehensive metabolic panel were within normal limits, and ECG showed normal sinus rhythm. Head CT scan was unremarkable. She was prescribed aspirin and admitted for evaluation. Symptoms lasted 48 hours. Brain MRI showed no acute infarction. Magnetic resonance angiography showed normal intracranial vessels and mild bilateral internal carotid disease. Echocardiography showed an ejection fraction of 55%–60% and no structural abnormalities, though the left atrium was not visualized. On telemetry, she had 2 self-limited episodes of asymptomatic paroxysmal supraventricular tachycardia. She started a low dose β-blocker.

Clinical Reasoning: A 50-year-old man with "elephantiasis" and headache.

A 50-year-old man with a medical history of “elephantiasis” of the legs, status post left above the knee amputation with prosthetic limb, and hypothyroidism presented with 1 week of headache and nausea. The headache was continuous, with gradual worsening over the 7 days prior to admission, and he had minimal relief with ibuprofen. On the second day, he developed nausea. He denied any history of headaches, blurred or double vision, numbness, weakness, tingling, loss of balance, vertigo, chest pain, palpitations, or shortness of breath. In the emergency room, he was afebrile with a heart rate of 78 beats per minute and regular, and a blood pressure of 132/78 mm Hg. General physical examination revealed right leg hypertrophy with hyperpigmentation, and edema more prominent distally (tree-barking) (figure 1). A comprehensive neurologic examination had normal results. Basic laboratory tests including complete blood count, basic metabolic panel, and thyroid tests were within normal limits. Head CT showed a hypodensity in the left cerebellar hemisphere (figure 1).