Journal of Stroke & Cerebrovascular Diseases

One-Year Atherothrombotic Vascular Events Rates in Outpatients with Recent Non-Cardioembolic Ischemic Stroke: The EVEREST (Effective Vascular Event REduction after STroke) Registry

2012-02-27

Background: Patients with recent ischemic stroke may have higher risk of atherothrombosis than stable patients with established vascular events. Our aims were to investigate 1-year atherothrombotic vascular event rates and to assess the risk factors for recurrent ischemic stroke in this population.Methods: This prospective cohort study was conducted between January 2007 and July 2009 at 313 hospitals in Japan. Outpatients who were at least 45 years of age and who had received oral antiplatelet therapy were enrolled within 2 weeks to 6 months from the last onset of noncardioembolic ischemic stroke. At 12 ± 3 months after enrollment, data on presence/absence of atherothrombotic vascular events were collected. The primary endpoint was the occurrence of fatal or nonfatal ischemic stroke.Results: A total of 3452 patients were enrolled, and 3411 patients who had baseline data were included in the analysis. The 1-year event rate was 3.81% (95% confidence interval 3.15-4.48%) for fatal or nonfatal ischemic stroke and 0.84% (95% confidence interval 0.52-1.15%) for all-cause mortality. The annual rate of recurrent ischemic stroke was significantly higher in patients who had ischemic stroke at least twice than in patients who had first-ever ischemic stroke (5.02% vs 3.59%; P = .0313). In the multivariable Cox regression analysis, recurrent ischemic stroke was significantly associated with age (P = .0033), the presence of diabetes (P = .0129), and waist circumference ≥80 cm (P = .0056).Conclusions: Patients with recent ischemic stroke have a higher risk of stroke recurrence than stable patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry even though they received antiplatelet therapy. The rigorous management of risk factors is needed.

Blood Pressure Fluctuations in Posterior Reversible Encephalopathy Syndrome

2011-05-03

Background: Posterior reversible encephalopathy syndrome (PRES) can be a consequence of hypertensive crisis and is often associated with rapid fluctuations in blood pressure (BP). However, the role of these BP changes in the pathogenesis of PRES has not been formally studied. Our objective was to analyze the relationship between BP fluctuations and the occurrence of PRES.Methods: We identified consecutive patients who developed PRES in the hospital and compared them with randomly selected controls matched for age, gender, and history of hypertension (HTN). Systolic BP (SBP) and diastolic BP (DBP) were collected at 2-hour intervals over a 48-hour window before the onset of PRES symptoms. A profile of changes in the values of SBP, DBP, mean arterial pressure (MAP), and pulse pressure (PP) over the 48-hour window was summarized for each individual by calculating a single number (M value) using the approach by Service et al. Comparisons of these summary numbers between the 2 groups (cases and controls) were made with the Wilcoxon signed rank test because of the smaller sample size and paired nature of the data. All tests were 2-sided, and P < .05 was considered statistically significant.Results: We analyzed the BP profiles in 25 cases of PRES and 25 controls. The median age of PRES patients was 54 years (range 31-72). Fourteen of them (56%) had a history of HTN. Hypertensive encephalopathy was considered the underlying cause of PRES in 13 patients (52%). At the time of the first symptoms of PRES, the mean SBP was 182 ± 20 mm Hg (range 218-145), DBP 95 ± 16 mm Hg (range 134-62), MAP 124 ± 15 (range 152-93), and PP 87 ± 18 (range 123-46). While BP was higher in PRES cases, the severity of HTN was variable and BP fluctuations were not significantly more common than in controls (P = .38 for SBP, .79 for DBP, .25 for MAP, and .73 for PP, respectively).Conclusions: Although acute HTN is frequent in patients with PRES, BP fluctuations do not appear to be more common in hospitalized patients who develop PRES compared with controls matched for age and history of HTN. Other predisposing factors must therefore contribute to the development of PRES.

Assessment of Long-Term Outcomes for the STRokE DOC Telemedicine Trial

2010-09-20

Telemedicine can provide stroke evaluations in locations with limited available expertise. The reliability of telestroke has been established. Decision making efficacy has been shown in the National Institutes of Health’s STRokE DOC trial. No prospective trial has assessed long-term telestroke outcomes, however. In an institutional review board-approved trial (NCT00936455), we contacted patients originally enrolled in the STRokE DOC trial. A telephone script was used to verify consent. Patients were asked standardized questions regarding disposition, modified Rankin Scale (mRS) score, mortality, and recurrent stroke for 2 retrospective time points (6 and 12 months postevent) and one current time point. Blind was maintained. Primary outcome measures of mortality and percent mRS score of 0-1 [%mRS(0-1)] at 6 months are reported. Wilcoxon’s rank-sum test was used for continuous variables, and Fisher’s exact was used for categorical variables. Of the original 222 participants, 75 patients or surrogates could be contacted. Mean time from enrollment was 3.96 ± 1.0 years (range, 2.33-5.45 years). Mean National Institutes of Health Stroke Scale (NIHSS) score was 8 ± 7 (5 ± 8 for telephone; 12 ± 8 for telemedicine; P = .002). The rate of intravenous recombinant tissue plasminogen activator (rt-PA) use was 31%. Six-month %mRS(0-1) outcome was not different, at 42%. Mortality after imputation to the entire study sample also was not different, at 18%. There was no difference in the rate of recurrent stroke (P = .61). Some 85% of patients were home at 6 months. This study reports a good 6-month outcome for stroke patients evaluated by telemedicine or telephone. This design is limited by the time since original enrollment and resultant inability to contact participants. Although these findings can add to the limited data on telemedicine outcomes, a prospective trial is needed.

Retrograde Memory in Cerebrovascular Disease and Alzheimer’s Disease

Daniel X. Capruso, Kerry deS. Hamsher — 2011-01-31

Retrograde memory is frequently tested in the mental status examination of patients with stroke or degenerative dementia. The goal of this experiment was to compare gradients of retrograde memory in patients without neurologic disease (n = 26), patients with cerebrovascular disease (n = 43), and patients with probable Alzheimer’s disease (n = 27). Patients were asked to recall and then name photographs of the 6 most recent US presidents. The free recall of patients with both cerebrovascular disease and probable Alzheimer’s disease formed an exaggeration of the normal forgetting curve seen in control patients, in that the most recent presidents were most likely to be remembered. For photo naming, control patients showed essentially no forgetting, whereas patients with cerebrovascular disease or Alzheimer’s disease had substantial memory loss with no temporal gradient. Alzheimer’s disease caused significantly worse retrograde memory loss than did cerebrovascular disease, despite the two groups’ equivalence in global intellectual functioning. Consistent with the focal or multifocal nature of cerebrovascular disease, stepwise multiple regression of retrograde memory on neuropsychological testing indicated that producing names by free recall was predicted by aphasic deficits, and that photo naming was predicted by visuoperceptual deficits. In Alzheimer’s disease, free recall was predicted primarily by deficits in verbal new learning, consistent with amnesia, whereas photo naming was predicted by loss of general knowledge, consistent with dementia. The results are consistent with the idea that free recall of names from the past is a form of episodic memory, whereas naming of famous faces from the past is a form of semantic memory.

Silent Infarction or White Matter Hyperintensity and Impaired Attention Task Scores in a Nondemented Population: The Osaki-Tajiri Project

2010-10-25

Whether silent infarction can be completely asymptomatic remains unclear. Although the central cholinergic system affects cognition, little attention has been given to infarction. We hypothesized that specific damage to the cholinergic pathways due to infarction or white matter hyperintensity (WMH) would deteriorate cognition, especially attention. A total of 502 representative elderly participants enrolled in the Osaki-Tajiri Project in 1998 were studied. Participants with focal neurologic signs or previous history of stroke or transient ischemic attack were excluded from the analysis. MRIs were available for all participants, and the Cholinergic Pathways Hyperintensities scale (CHIPS) was used to assess vascular damage in the cholinergic pathways. The Mini-Mental State Examination (MMSE), word fluency test, Digit Symbol test, and digit span test were used to assess global cognitive function and several aspects of attention. Participants were divided into 3 groups according to the comorbidity of cerebrovascular disease (CVD) and cholinergic involvement: non-CVD, CVD with cholinergic involvement [CVD-Ch(+)], and CVD without cholinergic involvement [CVD-Ch(−)]. Cognitive scores were compared among the 3 groups. In the non-CVD group, the correlations between cognitive function and the CHIPS score were examined. The CVD-Ch(+) group exhibited significantly lower scores for the Digit Symbol test compared with the other two groups, regardless of the MMSE score. In the non-CVD group, the CHIPS score of white matter changes was irreversibly correlated (ie, biologically meaningful) with the Digit Symbol score in participants age >80 years. Our findings suggest that silent infarction or WMH may deteriorate attention regardless of global cognitive function by interrupting the central cholinergic pathway.

Combined Surgical and Endovascular Approach to a Complex Dural Arteriovenous Fistula Involving the Superior Sagittal Sinus and Torcula

2010-10-04

A complex dural arteriovenous fistula (dAVF) may require complex treatment strategies to achieve successful obliteration. We describe a combined open surgical and endovascular approach to a dAVF involving the superior sagittal sinus (SS) and torcula. A 68-year-old male with Factor V Leiden mutation presented with altered mental status from venous hypertension secondary to a complex, high-flow Borden III dAVF with internal carotid and bilateral external carotid artery feeders draining into the SS and torcula. Because the venous channel to the recipient SS at the point of convergence of the AV shunting was not accessible transfemorally due to venous stenosis, a surgical strategy using a midline burrhole for direct catheterization of the SS was devised. A balloon was inflated in the sinus during arterial embolization. This technique was effective in achieving embolization of multiple arterial feeders via a single vessel injection. Covered Atrium iCasts were introduced in a telescoping fashion after angioplasty of the posterior SS–torcular junction in an attempt to functionally occlude further AV shunting. Postembolization angiography revealed greatly diminished AV shunting with improved intracranial transit time and retrograde cortical venous drainage. The patient was maintained on anticoagulation and made a complete recovery following the intervention; however, he subsequently deteriorated acutely, and died on postprocedure day 4. This case illustrates the difficulties associated with treating a complex AVF, describes a temporizing solution, and reports a potential complication from placing a covered stent in the SS.

Temporal Trends in Risk Factors and Outcome of Intracerebral Hemorrhage Over 18 Years at a Tertiary Care Hospital in Karachi, Pakistan

Mohammad Wasay, Ismail A. Khatri, Bhojo Khealani, Mohammad Afaq — 2010-10-25

Background: The purpose of this study was to analyze the baseline characteristics and outcomes of intracerebral hemorrhage (ICH) patients at our center over the last 18 years.Methods: Patients with ICH (first-time) were identified from medical records using International Classification of Diseases, Ninth Revision codes from 1988 to 2005. Patients were divided into 2 groups, with each group spanning 9 years based on the year of admission: the old group (admitted between 1988 and 1996) and the newer group (admitted between 1997 and 2005).Results: Out of 920 patients, the number of admissions with ICH increased from <40 per year (average) during 1988 to 1996 to >60 per year (average) during 1997 to 2005. The findings indicate that the percentage of cases in males decreased from 72% to 55% in the newer group as compared to the older group, while female ICH admissions increased from 28% to 45%. Mean age of ICH onset for both men and women decreased about 5 years, but this difference was not statistically significant. Frequency of diabetes (14% v 30%), dyslipidemia (3% v 18%), and the use of antihypertensive medications (29% v 69%) was higher in newer group, while the frequency of lobar hemorrhage was found to be reduced (40% v 20%) in newer group. Lower mortality (22% in the newer group v 32% in the older group) was noted. A decreased length of hospital stay for the newer group was recorded, but this difference was not found to be statistically significant.Conclusion: The mean age of ICH onset for both men and women has decreased about 5 years in the newer group. Men and women were equally affected in recent years as compared to male predominance in the older group.

Advanced Glycation End Products Increase Permeability of Brain Microvascular Endothelial Cells through Reactive Oxygen Species–Induced Vascular Endothelial Growth Factor Expression

2011-02-07

Background: Advanced glycation end products (AGEs) have been implicated as important factors in the pathogenesis of diabetic vascular complication. The aim of this study is to reveal the effect of AGEs on permeability of brain microvascular endothelial cells (BMECs) in order to assess its role in diabetic vascular complications.Methods: Permeability was determined by the flux of fluorescein isothiocyanate (FITC)-labeled dextran (4-kDa molecular weight) through endothelial cell monolayers on a transwell system and was compared between bovine BMECs (BBMECs) and bovine aortic endothelial cells (BAECs). The effect of AGEs on permeability was investigated in terms of the role of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS).Results: Permeability and VEGF expression were significantly increased by the addition of 100 μg/mL of glycer-AGEs in BBMECs. They also tended to be increased in BAECs, but not enough to make a significant difference. Simultaneous treatment with an anti-VEGF antibody suppressed the AGE-enhanced permeability. Furthermore, simultaneous treatment with a free radical scavenger, edaravone, also suppressed the AGE-enhanced permeability and the increase in VEGF mRNA levels and AGE-induced intracellular ROS overproduction.Conclusions: These results suggest that BMECs are more susceptible than aortic endothelial cells to AGE-enhanced permeability and that AGE-enhanced permeability is dependent on VEGF expression induced by ROS over production.

Stroke Risk Factors and Outcomes Among Various Asian Ethnic Groups in Singapore

2010-10-25

Data on interethnic differences in the Asian stroke population are limited. We evaluated the relationships among various cardiovascular risk factors, stroke subtypes, and outcomes in a multiethnic Singaporean population comprising consecutive ischemic stroke patients presenting to our tertiary center over a 1-year period. Strokes were classified based on criteria used in the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Functional independence at hospital discharge was defined as a modified Rankin Scale (mRS) score of 0-2. The ethnic distribution of the study population (n = 481; mean age, 64.1 ± 11.9 years) was 74% Chinese, 17% Malay, and 9% Indian. The prevalence of risk factors was similar in the 3 ethnic groups except for diabetes (Chinese, 39.8%; Malay, 67.5%; Indian, 52.3%; P < .001). Hypertension and hypercholesterolemia were the most common cardiovascular risk factors. Lacunar stroke was the most frequent stroke subtype (47.9%). Large-artery atherosclerotic infarctions were more prevalent in Indians (25.0%), whereas lacunar infarctions occured more frequently in Chinese (51.8%; P < .01). No differences in in-hospital mortality and functional independence at discharge were seen among the 3 ethnic groups. Despite the differences in risk factors and in stroke subtypes classified by location or underlying etiology, short-term outcome measures were similar in the 3 different Asian ethnicities in Singapore.

Elevated Anti–Heat Shock Protein 60 Antibody Titer is Related to White Matter Hyperintensities

2010-10-15

Background: There are many reports that the antibody against heat shock protein 60 (Hsp60) is present in most patients with coronary artery disease and atherosclerosis, and that its titer correlates with disease severity. However, few reports have described the association between anti-Hsp60 antibody and cerebrovascular disease.Methods: We determined the anti-Hsp60 antibody titer in patients with neurologic diseases and healthy subjects using enzyme-linked immunosorbent assay (ELISA) and evaluated their findings of brain magnetic resonance imaging (MRI) of the white matter. White matter hyperintensities (WMHs) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images were classified into 2 categories: periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The lesions in each category were then divided into 4 grades (grades 0-3) according to the Fazekas rating scale.Results: There were no significant differences in the titer between patients with neurologic diseases and healthy subjects. The mean grade of DWMHs (mean ± SD, 1.56 ± 0.70) was significantly higher in 18 subjects in the high-titer group (≥39.8 ng/mL; mean titer + 2 SD in sera from 23 healthy subjects) than in 86 subjects (mean ± SD, 0.09 ± 0.76) in the normal-titer group (<39.8 ng/mL; P < .003). The mean grade of PVHs (mean ± SD, 1.50 ± 0.71) was also significantly higher in the high-titer group than in the normal-titer group (mean ± SD, 1.17 ± 0.62; P < .02).Conclusions: A significant correlation was noted between anti-Hsp60 antibody titer and the severity of WMHs on brain MR images. We suggest that an elevated titer of the anti-Hsp60 antibody could be a risk factor for cerebral small-vessel disease.

Silent Cerebral Infarcts and Cerebral White Matter Lesions in Patients with Nonvalvular Atrial Fibrillation

Akiko Kobayashi, Masahiro Iguchi, Satoru Shimizu, Shinichiro Uchiyama — 2010-11-29

Background: Nonvalvular atrial fibrillation (NVAF) is a well-known strong risk factor for stroke, although few studies have examined silent cerebral ischemic lesions in patients with NVAF. We investigated silent cerebral infarcts (SCIs) and cerebral white matter lesions and risk factors for stroke in NVAF patients.Methods: Subjects included 71 consecutive patients with NVAF and 71 sex-and age-matched controls with sinus rhythm who had undergone MRI. Number, size, and localization of SCIs and severity of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) on magnetic resonance imaging were analyzed. The risk factors and CHADS2 score for stroke were also investigated.Results: The number of SCIs was significantly larger and the rates of SCIs in the cortex/subcortex and deep white matter were higher in the NVAF group than in the control group. The DSWMH grade was also significantly higher in the NVAF group. NVAF was an independent risk factor for SCIs and DSWMH. The number of cortical and subcortical SCIs was significantly correlated with CHADS2 score.Conclusions: Cortical/subcortical and deep white matter SCIs were more frequent and DSWMH grades were higher in NVAF patients compared with control subjects. CHADS2 score was an effective scheme not only in stroke risk but also in risk of SCI.

Safety of the Novel Protease-Activated Receptor-1 Antagonist Vorapaxar in Japanese Patients with a History of Ischemic Stroke

Yukito Shinohara, Shinya Goto, Masaki Doi, Peder Jensen — 2010-10-15

Background: Vorapaxar, formerly SCH 530348, is a novel, orally active, potent thrombin receptor inhibitor selective for the protease-activated receptor-1 (PAR-1). Previous phase II studies of patients undergoing urgent or scheduled percutaneous coronary intervention treated with vorapaxar plus aspirin and clopidogrel or ticlopidine showed a trend toward reducing major adverse cardiac events, particularly myocardial infarction, without increasing bleeding risk. The present study evaluated the safety of vorapaxar in Japanese patients with a history of ischemic stroke receiving aspirin.Methods: Ninety patients with previous ischemic stroke (≥14 days to <1 year before randomization) were randomized to receive vorapaxar (1 or 2.5 mg) or placebo once daily for 60 days. All patients received aspirin (75-150 mg/day). The primary endpoint was overall incidence of adverse events during the protocol-defined treatment phase (60 days).Results: Addition of vorapaxar to aspirin did not significantly increase the overall incidence of adverse events, including serious adverse events. None of the patients treated with vorapaxar plus aspirin experienced thrombolysis in myocardial infarction major or minor bleeding versus 1 patient treated with placebo. Nonfatal stroke occurred in 1 patient allocated to placebo and 1 patient allocated to vorapaxar.Conclusions: Vorapaxar used in combination with standard doses of aspirin was safe and well tolerated in Japanese subjects with a history of ischemic stroke.

A Malignant Case of Acute Promyelocytic Leukemia with Occlusion of Carotid Artery by Tumor Thrombus

Selena Nicholas-Bublick, John H. Irlam, Gretchen Tietjen — 2011-12-19

We report an unusual and malignant presentation of acute promyelocytic leukemia (APL) resulting in thrombosis of a cervicocephalic artery by tumor in a healthy 37-year-old woman. The patient’s rapid decline and multiorgan involvement proved to be a diagnostic and therapeutic challenge, and despite the efforts of a coordinated multidisciplinary health care team, she suffered a cardiac arrest and died within 48 hours of presentation to the emergency department. Autopsy revealed an APL-related tumor thrombus obstructing the left internal carotid artery, which to the best of our knowledge has not yet been described as a cause of fatal stroke.

Selective Infarction of the Anterior Genu Fornices Associated with Giant Cell Arteritis

Najib Murr, Pariwat Thaisetthawatkul, Jason Helvey, Pierre Fayad — 2010-10-01

We report a middle-aged woman presenting with acute confusion and anterograde amnesia. Magnetic resonance imaging revealed an acute infarction of the anterior genu fornices. Evaluation of an elevated erythrocyte sedimentation rate led to the diagnosis of giant cell arteritis (GCA). Cerebral infarction is a known complication of GCA; this is the first report of such an association with selective fornix infarction.

Scheie Syndrome Diagnosed After Cerebral Infarction

2010-12-20

We report a 41-year-old woman with Scheie syndrome diagnosed after cerebral infarction. She presented with acute onset dysarthria and right upper limb weakness. The neurologic findings revealed dysarthria, right central facial paralysis, mild right hemiparesis, and mild sensory impairment in the right arm and leg. Diffusion-weighted magnetic resonance imaging (MRI) showed subtle high signal lesions in the left corona radiata and posterior limb of the internal capsule. The diagnosis was made by a coarse facial appearance, claw hands, pigmentary degeneration of the bilateral retinas, and a deficiency of the enzymatic activity of lysosomal α-L-iduronidase. The patient was successfully treated with intravenous recombinant tissue plasminogen activator (rtPA) followed by enzyme replacement therapy. The prognosis of this disease would improve with enzyme replacement therapy. It is necessary to be aware of cerebral infarction in patients with Scheie syndrome.

Surgical Treatment of a Sylvian-Middle Fossa Dural Arteriovenous Fistula Draining into the Basal Vein of Rosenthal with Frontotemporal Craniotomy

Toshihide Tanaka, Naoki Kato, Takao Arai, Yuzuru Hasegawa, Toshiaki Abe — 2010-10-15

A 61-year-old man presented with left lower quadrianopsia caused by cerebral infarction in the right occpital lobe. Cerebral angiography revealed occlusion of right transverse sinus and Sylvian–middle fossa dural arteriovenous fistula (d-AVF) draining into the Sylvian vein and dilation of basal vein of Rosenthal. Surgical operation with right frontotemporal craniotomy was carried out to obliterate the fistula point and resection of the dura mater containing vasculature networks. Histologically, the thickening of walls of dural arteries and veins lacking internal elastica lamina were observed. Interestingly, the dura mater involving d-AVF was hyalinized and lacked collagen fibers, resembling local hypoxia and suggesting the possible role of dural hypoxia with pathogenesis of d-AVF. The present case indicates that open surgery can be effective for Sylvian–middle fossa d-AVF for the purpose of obliteration of fistula point and resection of the dura for histopathologic analyses.

Cerebral Venous Sinus Thrombosis in an Adult Patient Presenting as Headache and Acute Subdural Hematoma

Satoshi Takahashi, Jun Shinoda, Takuro Hayashi — 2010-12-27

We report a 55-year-old man with cerebral venous sinus thrombosis presenting as acute subdural hematoma. He was treated with an intravenous infusion of heparin sodium and the occluded superior sagittal sinus was recanalized. According to our literature review, acute subdural hematoma caused by cerebral venous sinus thrombosis is relatively rare, and only a single case has reported thus far. We speculate that dehydration was the reason for cerebral venous sinus thrombosis in the present case, and the sudden rise in intracranial pressure in addition to hemodynamic stress caused by cerebral venous sinus thrombosis resulted in the collapse of a bridging vein and caused an acute subdural hematoma.

Secondary Trigeminal Neuropathy and Neuralgia Resulting from Pontine Infarction

Ignacio Arrese — 2010-12-20

To the Editor, I have read the interesting article by Katsuno et al reporting a case of trigeminal neuralgia (TN) secondary to brain stem infarction, and have a few comments. The authors report the case of a 68-year-old man who presented with sharp pain on the right side of his face and in whom magnetic resonance imaging showed a wedge-shaped lesion without mass effect adjacent to the root entry zone of the right trigeminal nerve. The authors’ discussion of the physiopathology of the entity postulates that the infarction of the principal sensory trigeminal nucleus is the cause of the pain.

Erratum

2012-03-09

Significance of Magnetic Resonance Angiography—Diffusion Weighted Imaging Mismatch in Hyperacute Cerebral Infarction Stroke Cerebrovasc Dis 2012;21:108-113. In the article “Significance of Magnetic Resonance Angiography—Diffusion Weighted Imaging Mismatch in Hyperacute Cerebral Infarction” which was published in the February issue of Journal of Stroke & Cerebrovascular Diseases (Stroke Cerebrovasc Dis 2012;21:108-113), a correction omitted to Table 4. Please see correction in bold below.

Masthead

2012-05-01

Editorial Board