Interaction of incidental microbleeds and prior use of antithrombotics with early hemorrhagic transformation: Causative or protective?

BACKGROUND: Gradient echo (GRE) sequence of magnetic resonance imaging (MRI) is a sensitive tool to detect hemorrhagic transformation (HT) and old cerebral microbleeds (CMBs). Presence of CMBs and prior use of antithrombotics pose a risk of HT in ischemic stroke. We evaluated the association of CMBs and antithrombotic use with resultant HT in acute ischemic stroke (AIS). METHODS: This retrospective study included AIS patients admitted to our center between January 2009 and August 2010 who underwent GRE-weighted MRI within 48 h of admission. Demographic and clinical data including diabetes mellitus, hypertension, hyperlipidemia, prior intake of antiplatelets/anticoagulants/statins, and presence of CMBs at admission were collected and compared between patients who developed HT and those who did not. We did a multivariate analysis using logistic regression to assess the effect of CMBs and prior use of antithrombotic agents on the risk of development for early HT in ischemic stroke. RESULTS: Of 529 AIS patients, 81 (15%) were found to have HT during the initial hospital course. CMBs were found in only 9 of 81 patients (11%) with HT and in 40 out of remaining 448 patients (9%) who did not develop HT. The presence of CMBs was not associated with increased risk of HT (P = 0.53). However, prior use of antiplatelets (33% vs. 47% in the patients without HT, P = 0.02) was associated with decreased risk of HT in ischemic stroke. CONCLUSION: Presence of incidental CMBs was not associated with increased risk for early HT of an ischemic stroke. Interestingly, the prior intake of antiplatelets was found to be protective against HT of ischemic stroke.

Idiopathic Intracranial Hypertension Induced by Topical Application of Vitamin A.

A 21-year-old nonobese woman developed headaches and papilledema while excessively using 3 topical preparations of vitamin A. Neuroimaging studies were unremarkable and opening pressure on lumbar puncture was 300 mm H2O with normal cerebrospinal fluid composition. After discontinuation of the topical vitamin A preparations, the symptoms and signs of increased intracranial pressure resolved. The association of intracranial hypertension and topical vitamin A application has only been reported once previously.

Differential patterns of cortical reorganization following constraint-induced movement therapy during early and late period after stroke: A preliminary study.

OBJECTIVE: Constraint-induced movement therapy (CIMT) has been shown to improve upper extremity voluntary movement and change cortical movement representation after stroke. Direct comparison of the differential degree of cortical reorganization according to chronicity in stroke subjects receiving CIMT has not been performed and was the purpose of this study. We hypothesized that a higher degree of cortical reorganization would occur in the early (less than 9 months post-stroke) compared to the late group (more than 12 months post-stroke). METHODS: 17 early and 9 late subjects were enrolled. Each subject was evaluated using transcranial magnetic stimulation (TMS) and the Wolf Motor Function Test (WMFT) and received CIMT for 2 weeks. RESULTS: The early group showed greater improvement in WMFT compared with the late group. TMS motor maps showed persistent enlargement in both groups but the late group trended toward more enlargement. The map shifted posteriorly in the late stroke group. The main limitation was the small number of TMS measures that could be acquired due to high motor thresholds, particularly in the late group. CONCLUSION: CIMT appears to lead to greater improvement in motor function in the early phase after stroke. Greater cortical reorganization in map size and position occurred in the late group in comparison. SIGNIFICANCE: The contrast between larger functional gains in the early group vs larger map changes in the late group may indicate that mechanisms of recovery change over the several months following stroke or that map changes are a time-dependent epiphenomenon.

Prevalence of symptoms and risk of sleep apnea in patients with ruptured cerebral aneurysm.

OBJECTIVE: To determine the prevalence of symptoms and risk of obstructive sleep apnea (OSA) among patients with ruptured cerebral aneurysms. METHODS: In this case-control study, a validated Arabic version of the Berlin Questionnaire (BQ) was administered to patients admitted to King Fahd Medical City, Riyadh, Saudi Arabia with cerebral aneurysms between January 2006 and July 2011 (n=53). The same questionnaire was administered to a control group comprised of patients attending primary health care clinics who were matched for age, body mass index (BMI), and gender (n=212). RESULTS: The mean age of patients with ruptured cerebral aneurysms was 50.7 +/- 15.2 years, and the mean BMI was 27.9 +/- 4.8 kg/m2. In this group, 75.5% complained of snoring compared with 46.7% of the controls (p=0.000). Hypertension was present in 67.9% of cases compared with 30.2% of the controls (p=0.000). Based on the BQ scores, 60.4% of the cases were considered to be at high risk for OSA compared with 31.6% of the controls (p=0.000). CONCLUSION: The prevalence of OSA symptoms among patients with ruptured cerebral aneurysms is very high. Almost 60% of patients with ruptured cerebral aneurysms are at risk for OSA.

Determinants of neurologic deterioration and stroke-free survival after spontaneous cervicocranial dissections: a multicenter study.

Patients with spontaneous cervicocranial dissection (SCCD) may experience new or recurrent ischemic events despite antiplatelet or anticoagulant therapy. Treatment with stent placement is an available option; however, the literature on patient selection is limited. Thus, identifying patients at high risk for neurologic deterioration after SCCD is of critical importance. The present study examined the rate of neurologic deterioration in medically treated patients with SCCD and evaluated demographic, clinical, and radiologic factors affecting this deterioration. We retrospectively identified consecutive patients with SCCD over a 7-year period from 3 medical institutions, and evaluated the relationships between demographic data, clinical characteristics, and angiographical findings and subsequent neurologic outcomes. Neurologic deterioration was defined as transient ischemic attack (TIA), ischemic stroke, or death occurring during hospitalization or within 1 year of diagnosis. Kaplan-Meier curves were used to determine neurologic event-free survival up to 12 months. A total of 69 patients (mean age, 47.8 ± 14 years; 45 males) with SCCD were included in the study. Eleven patients (16%) experienced in-hospital neurologic deterioration (TIA in 9, ischemic stroke in 1) or death (1 patient). An additional 8 patients developed neurologic deterioration within 1 year after discharge (TIA in 5, ischemic stroke in 2, and death in 1). The overall 1-year event-free survival rate was 72%. Women (P = .046), patients with involvement of both vertebral arteries (P = .02), and those with intracranial arterial involvement (P = .018) had significantly higher rates of neurologic deterioration. Our findings indicate that neurologic deterioration is relatively common after SCCD despite medical treatment in women, patients with bilateral vertebral artery involvement, and those with intracranial vessel involvement.

Factors associated with rapid neurological improvement 24 h following intra-arterial thrombolytic treatment for acute ischemic stroke.

BACKGROUND AND PURPOSE: Significant 24 h improvement is the strongest indicator of functional recovery following thrombolytic treatment for acute ischemic stroke. This study sought to analyze factors contributing to rapid neurological improvement (RNI) following intra-arterial thrombolytic treatment (IATT). METHODS: Angiograms and clinical information derived from consecutive patients receiving treatment initiated within 6 h of stroke onset were retrospectively reviewed. RNI was defined as at least 50% 24 h improvement on the National Institutes of Health Stroke Scale score. Logistic regression analysis identified factors associated with RNI. Variables tested included: age, gender, serum glucose, platelet count, pial collateral formation, presenting National Institutes of Health Stroke Scale score, time to treatment, extent of reperfusion, site and location of occlusion, treatment agent and systolic blood pressure. RESULTS: Greater than 50% reperfusion of the involved territory, time to treatment within 270 min and good pial collateral formation (large penumbra zone) significantly predicted RNI. RNI occurred in 31% of the 112 patients studied. RNI occurred in 21/26 (80.8%) patients exhibiting all three favorable variables whereas patients with only one favorable variable had a 6.5% chance of RNI. 94% of patients displaying RNI had a modified Rankin Scale score of 2 or less at 3 months compared with 28.6% without RNI. CONCLUSIONS: RNI following IATT for stroke is more likely when at least two of the following are present: good reperfusion, good pial collateral formation and treatment within 4.5 h of symptom onset, and is strongly predictive of 3 month outcomes. Important to clinical management, IATT may need to be reconsidered in patients with poor pial collateral formation if time to treatment exceeds 4.5 h.

Comparison of single versus multiple spontaneous extra- and/or intracranial arterial dissection.

BACKGROUND: Anecdotal data suggest that approximately 20% of patients with a spontaneous extra- and/or intracranial arterial dissection have multiple arterial involvement. Limited data exist regarding the clinical and angiographic characteristics of patients with multiple arterial dissections. We compared the clinical and angiographic features of patients with spontaneous multiple extra- and/or intracranial arterial dissections with those who have a single arterial dissection. METHODS: A retrospective chart review of the consecutive ischemic stroke database over a 7-year period, maintained at 2 institutions, was conducted to identify patients with spontaneous extra- and/or intracranial arterial dissection. The patients' clinical characteristics and angiographic features (including the artery affected, presence of pseudoaneurysm, fibromuscular dysplasia, and degree of stenosis) were analyzed. RESULTS: A total of 76 patients were admitted with spontaneous extra- and/or intracranial arterial dissection; 46 dissections were confirmed with 4-vessel cerebral angiography. Multiple arterial dissections were found in a total of 10 (22%) patients. Involvement of multiple arteries was more prevalent in the young, when compared to a single spontaneous arterial dissection (7 [70%] in patients <45 years of age v 11 [31%]; P = .03). Patients with multiple arterial dissections had a higher proportion of pseudoaneurysms (9 [90%] v 11 [31%]; P = .001), a higher prevalence of underlying fibromuscular dysplasia (3 [30%] v 3 [8%]; P = .11), and were more likely to involve the posterior circulation (P < .0001). CONCLUSIONS: The presence of multiple, simultaneous spontaneous extra- and/or intracranial arterial dissections must be considered when a single spontaneous arterial dissection is identified.

Racial/ethnic disparities in emergency department waiting time for stroke patients in the United States.

Emergency department waiting time (EDWT), the time from arrival at the ED to evaluation by an emergency physician, is a critical component of acute stroke care. We assessed racial/ethnic differences in EDWT in a national sample of patients with ischemic or hemorrhagic stroke. We identified 543 ED visits for ischemic stroke (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 433.x1, 434.xx, and 436.xx) and hemorrhagic stroke (ICD-9-CM codes 430.xx, 431.xx, and 432.xx) in persons age ≥ 18 years representing 2.1 million stroke-related ED visits in the United States using the National Hospital Ambulatory Medical Care Survey for years 1997-2000 and 2003-2005. Using linear regression (outcome, log-transformed EDWT) and logistic regression (outcome, EDWT > 10 minutes, based on National Institute of Neurological Disorders and Stroke guidelines), we adjusted associations between EDWT and race/ethnicity (non-Hispanic whites [designated whites herein], non-Hispanic blacks [blacks], and Hispanics) for age, sex, region, mode of transportation, insurance, hospital characteristics, triage status, hospital admission, stroke type, and survey year. Compared with whites, blacks had a longer EDWT in univariate analysis (67% longer, P = .03) and multivariate analysis (62% longer, P = .03), but Hispanics had a similar EDWT in both univariate analysis (31% longer, P = .65) and multivariate analysis (5% longer, P = .91). Longer EDWT was also seen with nonambulance mode of arrival, urban hospitals, or nonemergency triage. Race was significantly associated with EDWT > 10 minutes (whites, 55% [referent]; blacks, 70% [P = .03]; Hispanics, 62% [P = .53]). These differences persisted after adjustment (blacks: odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.05-4.09; Hispanics: OR = 1.07, 95% CI = 0.52-2.22). Blacks, but not Hispanics, had significantly longer EDWT than whites. The longer EDWT in black stroke patients may lead to treatment delays and sub-optimal stroke care.

The role of antithrombotics in secondary stroke prevention.

Antithrombotic therapy plays a key role in secondary ischemic stroke prevention. A multitude of antithrombotic agents exist with varying pharmacologic, efficacy, and safety profiles. In this review, the authors discuss the mechanisms of antithrombotic therapy, summarize the data on commonly used agents, and introduce emerging antithrombotic medications.

Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke.

BACKGROUND: Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke. OBJECTIVE: The present study represents the first multi-center effort to measure cortical reorganization induced by CIMT in subjects who are in the subacute stage of recovery. METHODS: A total of 30 stroke subjects in the subacute phase (>3 and <9 months poststroke) were recruited and randomized into experimental (receiving CIMT immediately after baseline evaluation) and control (receiving CIMT after 4 months) groups. Each subject was evaluated using transcranial magnetic stimulation (TMS) at baseline, 2 weeks after baseline, and at 4-month follow-up (ie, after CIMT in the experimental groups and before CIMT in the control groups). The primary clinical outcome measure was the Wolf Motor Function Test. RESULTS: Both experimental and control groups demonstrated improved hand motor function 2 weeks after baseline. The experimental group showed significantly greater improvement in grip force after the intervention and at follow-up (P = .049). After adjusting for the baseline measures, the experimental group had an increase in the TMS motor map area compared with the control group over a 4-month period; this increase was of borderline significance (P = .053). CONCLUSIONS: Among subjects who had a stroke within the previous 3 to 9 months, CIMT produced statistically significant and clinically relevant improvements in arm motor function that persisted for at least 4 months. The corresponding enlargement of TMS motor maps, similar to that found in earlier studies of chronic stroke subjects, appears to play an important role in CIMT-dependent plasticity.

Clinical and radiological outcomes of acute ischemic stroke patients without angiographic occlusion on digital subtraction angiogram. A pooled analysis of case series.

INTRODUCTION: Approximately 20-30% of the patients with acute ischemic stroke do not have any occlusion demonstrated on initial digital subtraction angiography (DSA). We sought to determine the risk and rates of cerebral infarction and favorable neurological outcome in this group of acute ischemic stroke patients. MATERIALS AND METHODS: Patients were identified from a prospectively maintained stroke database and from literature search of MEDLINE, PubMed, and Cochrane databases. All patients had initial neurological assessment on National Institutes of Health Stroke Scale (NIHSS). Patients then underwent DSA after initial head computed tomography (CT) scans. Follow-up radiological assessment at 24-72 h was performed with CT and magnetic resonance imaging scans. Association of stroke risk factors with clinical and radiological outcomes was estimated. RESULTS: A total of 81 patients was analyzed (mean age 63 years; 28 were women). The median NIHSS score was 8 (range 2-25). None of the patients received either intravenous or intra-arterial thrombolytic. Cerebral infarction was detected in 62 (76%) of the 81 patients. Twenty-four to 48-h NIHSS was available for 51 patients only. Neurological improvement was observed in 22 (43%) of the 51 patients. Favorable outcome ascertained at 3-month follow-up was seen in 48 (59%) of the 81 patients. After adjusting for age, sex, and baseline NIHSS, male patients [odds ratio (OR) 4.5 (1.4-14.3), p value = 0.01] and patients with age >or=65 [OR 4.3 (1.2-16.2), p value = 0.03] have a higher risk of cerebral infarcts on the follow-up imaging. Similarly, patients who presented with <10 NIHSS had a better 3-month outcome than those with >10 NIHSS [OR 0.21 (0.08-0.61), p value = 0.004]. CONCLUSION: Ischemic stroke patients without arterial occlusion on DSA have a higher risk of cerebral infarction and disability particularly in men, patients over 65 years of age and with NIHSS >or=10. The cause of infarction may have been arterial obstruction with spontaneous recanalization or small vessel occlusion not visible on DSA.

Qureshi grading scheme predicts subsequent volume of brain infarction following intra-arterial thrombolysis in patients with acute anterior circulation ischemic stroke.

BACKGROUND: The importance of the site of occlusion and the presence or absence of collaterals on initial angiography in patients with acute ischemic stroke has been recognized. Qureshi recently proposed a scheme that categorizes patients with ischemic stroke based on findings observed on initial angiography. METHODS: We determined the relationship between severity of angiographic occlusion using Qureshi grading scheme and volume of brain infarction on follow-up computed tomography in 55 patients with anterior circulation ischemic stroke who underwent intra-arterial thrombolysis. RESULTS: A strong association was observed between Qureshi grades and volume of brain infarction (F ratio 6.2, P= .0005) after adjusting for patients' age, sex, National Institutes of Health Stroke Scale (NIHSS) score, thrombolytic used, and time interval between symptom onset and angiography. The relationship persisted after further adjustment for final angiographic recanalization (F ratio 5.1, P= .001). A significant relationship between initial grades and volume of brain infarction was separately observed in both patients with or without recanalization following treatment. CONCLUSIONS: Qureshi grading scheme can be effectively used to stratify patients with anterior circulation ischemic stroke undergoing intra-arterial thrombolysis using initial angiographic findings.

Mode of arrival to the emergency department of stroke patients in the United States.

BACKGROUND: The modality of transport to the emergency department has implications for triage, evaluation, and treatment of patients with stroke. We performed this study to determine the national trends in modes of arrival in patients with stroke and its association with emergency department evaluation in a nationally representative sample of United States. METHODS: We used the data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). The NHAMC is one of the largest studies designed to provide utilization and provision of services in hospital emergency departments (ED). Patients were categorized into three modes of arrival: 1) ambulance, either air or ground; 2) walk-in, this include car, taxi, bus, or foot; and 3) public services such as police car or social service vehicle/Unknown. RESULTS: Of the 630,402 patients evaluated with stroke in the ED, the mode of arrival was by ambulance [331,760 (53%)], walk-in [271,268 (43%)], and public services/unknown [27374 (4%)]. The mean time for evaluation by a physician was 30±37 minutes, 34±44 minutes, and 55±105 minutes for ambulance, walk-in (P=0.535), and public services/unknown (P=0.664) mode of arrival, respectively. There was a trend for more frequent utilization of brain imaging in the patients presenting by ambulance (73%) compared to walk-in (63%, P=0.64) and public services/unknown (59%, P=0.5). Patients transferred by ambulance were more often admitted to the intensive care unit (11%) compared to walk-in (0.2%, P=0.02) and public services/unknown (6%, P=0.47). CONCLUSION: Although arrival by ambulance was associated with a higher level of care, a prominent proportion of patients with suspected stroke are not arriving by ambulance to the ED.

Intra-arterial reteplase and intravenous abciximab in patients with acute ischemic stroke: an open-label, dose-ranging, phase I study.

OBJECTIVE: New approaches are focusing on using a combination of medication that lyse fibrin and prevent aggregation of platelets to achieve higher rates of recanalization and improved clinical outcomes. METHODS: A prospective, nonrandomized, open-label trial evaluated the safety of an escalating dose of reteplase in conjunction with intravenous abciximab (platelet glycoprotein IIb/IIIa inhibitor) in patients with acute ischemic stroke (3-6 h after symptom onset). The primary endpoint was symptomatic intracerebral hemorrhage at 24 to 72 hours, and secondary endpoints were partial or complete recanalization (> or = one grade improvement), early neurological improvement (decrease in National Institutes of Health Stroke Scale > or = 4 at 24 h), and favorable outcome at 1 month (defined by modified Rankin scale < or = 2). RESULTS: A total of 20 patients (mean age, 65 yr; 13 men) were recruited. Five patients were recruited in each of the escalating tiers of intra-arterial reteplase (0.5, 1, 1.5, and 2 units). Intravenous abciximab (0.25 mg/kg bolus followed by 0.125 mug/kg/min) was successfully administered in 18 out of 20 patients. The safety stopping rule was not activated in any of the tiers. One symptomatic intracerebral hemorrhage was observed in one of the 20 patients (in the 1-unit tier). Partial or complete recanalization was observed in 13 of the 20 patients. Thirteen patients demonstrated early neurological improvement, and favorable outcome at 1 month was observed in six patients. CONCLUSION: In this study, a combination of intra-arterial reteplase and intravenous abciximab was safely administered to patients with ischemic stroke presenting between 3 and 6 hours after symptom onset.

Primary stroke center: basic components and recommendations.

Stroke is the leading cause of disability and the third leading cause of death in the United States. The brain attack coalition (BAC), whose members belong to several professional medical societies, formed a working group to explore the factors and elements that are associated with better clinical outcome after acute stroke. In the year 2000, the BAC published the recommendations for primary stroke centers (PSC). The primary goals for the PSC are to improve and to standardize stroke care. Convinced by the compelling data on the PSC, the Joint Commission on Accreditation of Healthcare Organization adopted the BAC recommendations and started certifying hospitals as designated PSCs. Many hospitals are already certified and numerous others are currently seeking certification. The BAC is now working on the recommendations for a comprehensive stroke center. The nihilism which dominated the stroke field has finally been replaced by remarkable progress and better understanding of stroke and stroke treatment.

A prospective multicenter study to evaluate the feasibility and safety of aggressive antihypertensive treatment in patients with acute intracerebral hemorrhage.

The authors performed a multicenter prospective observational study to evaluate the feasibility and safety of intravenous antihypertensive protocol for acute hypertension in patients with intracerebral hemorrhage (ICH). Twenty-seven patients with ICH and acute hypertension (mean age 61.37 +/- 14.27; 10 were men) were treated to maintain the systolic blood pressure (BP) below 160 mm Hg and diastolic BP below 90 mm Hg within 24 hours of symptom onset. Neurological deterioration (defined as a decrease in initial Glasgow Coma Scale score > or = 2) was observed in 2 (7.4%) of 27 patients during treatment. Among patients who underwent follow-up computed tomography, hematoma expansion (more than 33% increase in hematoma size at 24 hours) was observed in 2 (9.1%) of 22 patients. Patients treated within 6 hours of symptom onset were more likely to be functionally independent (modified Rankin scale < or = 2) at 1 month compared with patients who were treated between 6 and 24 hours (8 of 18 versus 0 of 9,P = .03). Aggressive pharmacological treatment of acute hypertension in patients with ICH can be initiated early with a low rate of neurological deterioration and hematoma expansion.

Acute treatment for ischemic stroke in 2004.

The last decade witnessed significant and unprecedented advances in the treatment of acute ischemic stroke. Intravenous tissue plasminogen activator and defibrinogenating agent are both now approved by the Food and Drug Administration for treatment of acute ischemic stroke within 3 h of symptom onset. Trials involving intra-arterial thrombolysis have demonstrated clinical benefit in patients treated within 6 h of symptom onset. The future for the development of new and better treatment for ischemic stroke looks very promising. Currently, induced hypothermia, laser evaporation, mechanical thrombectomy, angioplasty with stent placement, the combination of neuroprotective agents with thrombolysis, and the combination of intravenous with intra-arterial thrombolysis are being investigated.