Dan J. Capampangan

Statins and Intracerebral Hemorrhage: Collaborative Systematic Review and Meta-analysis

Background— A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. Methods and Results— We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86–1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81–1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41–0.88). Substantial statistical heterogeneity was evident for the case-control studies (I2=66%, P=0.01), but not for the cohort studies (I2=0%, P=0.48) or randomized trials (I2=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. Conclusions— We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.Background— A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. Methods and Results— We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86–1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81–1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41–0.88). Substantial statistical heterogeneity was evident for the case-control studies (I2=66%, P =0.01), but not for the cohort studies (I2=0%, P =0.48) or randomized trials (I2=30%, P =0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. Conclusions— We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs. # Clinical Perspective {#article-title-52}

Is obstructive sleep apnea an independent risk factor for stroke? A critically appraised topic.

Background:Obstructive sleep apnea (OSA) is associated with hypertension, atrial fibrillation, coronary artery disease, congestive heart failure, and diabetes. These disorders are also risk factors for stroke. Objective:To determine whether OSA increases the risk of stroke independently of other cerebrovascular risk factors. Methods:The objective was addressed through the development of a structured critically appraised topic. This evidence-based methodology included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of sleep medicine and vascular neurology. Results:A large observational cohort study was selected and appraised to address this prognostic question. The unadjusted analysis revealed that OSA (apnea-hypopnea index >5) was associated with stroke or death from any cause (hazard ratio, 2.24; 95% confidence interval [CI], 1.30–3.86; P = 0.004). The adjusted OSA analysis retained a statistically significant association with stroke or death (hazard ratio, 1.97; 95% CI, 1.12–3.48; P = 0.01). In separate unadjusted analyses, OSA was associated with death and stroke with relative risks of 1.68 (95% CI, 1.10–2.25) and 5.16 (95% CI, 3.72–6.60), respectively. Conclusions:OSA independently contributes to stroke risk.

Telemedicine versus telephone for remote emergency stroke consultations: a critically appraised topic.

Background:The rate of patients being treated with thrombolytic therapy is low, in part, due to a shortage of vascular neurologists, especially in rural communities. Two-way audio-video communication through telemedicine has been demonstrated to be a reliable method to assess neurologic deficits due to stroke and maybe more efficacious in determining thrombolytic therapy eligibility than telephone-only consultation. Objective:To determine the efficacy of telemedicine versus telephone-only consultations for decision making in acute stroke situations. Methods:The objective was addressed through the development of a structured, critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarian, and clinical content experts in the fields of vascular neurology, emergency medicine, and telemedicine. Participants started with a clinical scenario and a structured question, devised search strategies, located and compiled the best evidence, performed a critical appraisal, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. Results:A single randomized, blinded, prospective trial comparing telephone-only consultations to telemedicine consultations for acute stroke was selected and appraised. Correct acute stroke treatment decisions were made more often in the telemedicine group versus the telephone-only group (98% vs. 82%, [number needed to assess = 6]). Stroke telemedicine when compared with telephone-only consultations was more sensitive (100% vs. 58%), more specific (98% vs. 92%), had a more favorable positive likelihood ratio (LR: 41 vs. 7) and negative likelihood ratio (LR: 0 vs. 0.5), and had higher predictive values (positive predictive value 94% vs. 76%, and negative predictive value 100% vs. 84%) for the determination of thrombolysis eligibility. Conclusion:Stroke telemedicine when compared with telephone-only consultations is an effective method to determine thrombolysis eligibility for acute stroke patients who do not have immediate access to a stroke neurologist.

Sleep apnea and white matter disease in hypertensive patients: a case series.

Obstructive sleep apnea (OSA) is associated with hypertension (HTN) and cardiovascular disease. Transient episodes of hypoxia, hypercapnia, and blood pressure elevation during OSA may lead to neural damage and subsequently white matter disease (WMD). As WMD is usually the result of chronic small vessel ischemia, a relationship between OSA and cerebrovascular disease may exist. This case series aimed to establish a relationship between OSA and WMD. Sixty-two patients without cerebrovascular disease who had both a polysomnogram and brain magnetic resonance imaging were identified. All patients carried the diagnosis of HTN. WMD was evaluated using the age-related white matter changes scale. Although half of the study population had WMD on magnetic resonance imaging, no association was found between WMD with severity of OSA (P=0.9). Our results are limited by the small sample size and by coexistent HTN in all patients. Further studies are needed to elucidate the relationship between OSA and WMD, especially among nonhypertensive patients. Future research should also address if OSA treatment has any effect on WMD.

New-onset atrial fibrillation in severe sepsis and risk of stroke and death: A critically appraised topic

Background:Severe sepsis has been associated with an increased risk of new-onset arrhythmias, namely atrial fibrillation (AF). Single-center and small-center studies suggest that new-onset AF is associated with higher mortality and prolonged hospitalization during severe sepsis. However, the relationship between new-onset AF in severe sepsis to prognosis is unknown. Objective:To determine whether new-onset AF increases the risk of stroke and death in severe sepsis. Methods:The objective was addressed through the development of a structured, critically appraised topic. This incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and fellow-level neurologists, a medical librarian, clinical epidemiologists, and context experts in the fields of vascular neurology, hospital neurology, critical care medicine, and cardiovascular medicine. Results:A recent retrospective, population-based cohort study was selected and appraised to address this prognostic question. Patients were obtained from the California State Inpatient Database administrative claims data from nonfederal acute care hospitals from January 1 through December 31, 2007. Of the 3,144,787 patients, 49,082 (1.56%) had severe sepsis, defined by the validated International Classification of Disease, 9th Revision, Clinical Modification code 995.92. The a priori outcome measures included in-hospital ischemic stroke and mortality. New-onset AF occurred in 5.9% of patients with severe sepsis versus 0.65% of patients without severe sepsis [odds ratio, 6.82; 95% confidence interval (CI), 6.52-7.11; P<0.001]. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital ischemic stroke (2.6% vs. 0.6% strokes; adjusted odds ratio, 2.70; 95% CI, 2.05-3.57; P<0.001) and in-hospital mortality (56% vs. 39% deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P<0.001). Findings were robust across 2 separate definitions of severe sepsis and multiple sensitivity analyses. Conclusions:In patients with severe sepsis, new-onset AF seems to increase the risk of in-hospital stroke and mortality compared with patients with no or preexisting AF.

Does prophylactic postoperative hypervolemic therapy prevent cerebral vasospasm and improve clinical outcome after aneurysmal subarachnoid hemorrhage

Background:Delayed cerebral vasospasm is a common cause of morbidity and mortality after acute aneurysmal subarachnoid hemorrhage. Hypovolemia and fluid restriction are risk factors for delayed vasospasm; hypervolemic therapeutic approaches are commonly used in patients with subarachnoid hemorrhage to prevent and to treat cerebral vasospasm. Objective:To determine if postoperative prophylactic hypervolemic therapy prevents cerebral vasospasm and improves clinical outcome in patients with aneurysmal subarachnoid hemorrhage. Methods:The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. Results:One randomized controlled trial addressed the questions. There was no difference in the incidence of symptomatic cerebral vasospasm (20% each) or clinical outcome at 14 days and 3 months between the hypervolemic and normovolemic groups. Hypervolemic therapy also had no effect on measures of cerebral blood flow. A second quasi-randomized trial reached the same conclusions. Conclusion:Available evidence is insufficient to support use of prophylactic hypervolemic therapy after surgery in patients with aneurysmal subarachnoid hemorrhage. Although completed studies may be insufficiently sensitive (underpowered) to detect a treatment effect, the magnitude of any as yet undetected benefit of prophylactic hypervolemic therapy is likely modest and its risks have not been systematically evaluated.

What is the effect of low-molecular weight heparin for venous thromboembolism prophylaxis compared with mechanical methods, on the occurrence of hemorrhagic and venous thromboembolic complications in patients with intracerebral hemorrhage? A critically appraised topic.

BackgroundPatients with intracerebral hemorrhage (ICH) are at risk for venous thromboembolic (VTE) complications after stroke. The dilemma remains on whether it is safe to initiate low-dose low-molecular weight heparin (LMWH) in patients with ICH without risking expansion of the initial bleed. ObjectiveTo critically assess current evidence regarding the safety of low-dose LMWH in the prevention of VTE complications in patients with acute ICH. MethodsThe objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular and hospital neurology. ResultsA recent quasi-randomized controlled trial was selected for critical appraisal. This trial assigned 75 ICH patients to subcutaneous LMWH or long compression stockings for deep venous thrombosis and pulmonary embolism prophylaxis. In patients who received low-dose LMWH, there was no hematoma enlargement at 72 hours, day 7, or day 21 compared with the compression stocking group. There was hematoma enlargement in 9 patients at 24 hours, 6 of which were in the LMWH group, but this was before the initiation of the LMWH, which occurred at 48 hours. Adverse events were VTE complications in 4 of 39 patients in the LMWH group and in 3 of 36 patients in the long compression stocking group. ConclusionsInitiation of low-dose LMWH in spontaneous ICH patients for the purpose of VTE prophylaxis is likely safe. However, a clinical decision based solely on the results of this study cannot be made due to numerous methodological and design shortcomings. A well-designed randomized controlled trial is still needed to answer this clinical question.

Olfactory and Gustatory Hallucinations Presenting as Partial Status Epilepticus Because of Glioblastoma Multiforme

Olfactory and gustatory hallucinations are not often encountered in the acute care setting but may represent the subtle presenting features of a significant underlying disease process. We describe a patient whose most striking presenting symptoms were of olfactory and gustatory hallucinations and in whom the diagnosis and treatment of a new brain tumor and partial status epilepticus occurred entirely in the emergency department. The lesion was subsequently identified as glioblastoma multiforme involving the hippocampus and amygdala.

Statins and Intracerebral Hemorrhage

Background— A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. Methods and Results— We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86–1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81–1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41–0.88). Substantial statistical heterogeneity was evident for the case-control studies (I2=66%, P=0.01), but not for the cohort studies (I2=0%, P=0.48) or randomized trials (I2=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. Conclusions— We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.Background— A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. Methods and Results— We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86–1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81–1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41–0.88). Substantial statistical heterogeneity was evident for the case-control studies (I2=66%, P =0.01), but not for the cohort studies (I2=0%, P =0.48) or randomized trials (I2=30%, P =0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. Conclusions— We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs. # Clinical Perspective {#article-title-52}

Teaching NeuroImages: Hyperdense posterior cerebral artery sign

A 38-year-old man presented to the emergency department with right-sided weakness, sensory loss, and hemianopsia. CT head showed a left hyperdense posterior cerebral artery sign (HPCAS) (figure 1). CT angiogram of the head confirmed a left posterior cerebral artery (PCA) occlusion (figure 2). MRI demonstrated a left PCA infarct. Transesophageal echocardiogram revealed an atrial septal aneurysm and patent foramen ovale. He was treated with antiplatelet therapy. The HPCAS has been considered a marker for acute ischemia in the PCA territory.1 Recognizing the HPCAS on CT in acute stroke may help in the diagnosis and treatment of thromboembolic PCA branch occlusion.