TIA Patients Research Articles

Recurrent cerebral ischemia in medically treated patent foramen ovale

Among patients with a patent foramen ovale (PFO) and a prior cryptogenic ischemic stroke or TIA, the absolute and relative risk of recurrent events is unclear. We conducted a systematic review and meta-analysis of clinical studies in any language published up to February 2008. We included studies reporting original data on recurrent cerebrovascular events in patients with prior cryptogenic stroke or TIA and PFO. Two authors independently extracted data and evaluated study quality. We identified 15 eligible studies, four with a non-PFO comparison group. In these four studies, the pooled relative risk (RR) for recurrent ischemic stroke or TIA in patients with vs without a PFO was 1.1 (95% confidence interval [CI] 0.8 to 1.5). For ischemic stroke, the pooled RR was 0.8 (95% CI 0.5 to 1.3). We tabulated the absolute rate of recurrent events in all 15 studies. The pooled absolute rate of recurrent ischemic stroke or TIA in patients with PFO was 4.0 events per 100 person-years (95% CI 3.0 to 5.1) while the rate of recurrent ischemic stroke was 1.6 events per 100 person-years (95% CI 1.1 to 2.1). In medically treated patients with prior cryptogenic stroke, while the absolute rate of recurrent events is variable, available evidence does not support an increased relative risk of recurrent ischemic events in those with vs without a patent foramen ovale. Patent foramen ovale closure in these patients cannot be recommended until the results of ongoing clinical trials are reported.

PP5. Urgent Surgical Treatment of Carotid Stenosis in Patients with Acute Neurologic Deficits

Late results from NASCET and ECST showed a greater benefit for surgery if performed within 4 weeks from symptoms. Recent studies have emphasized the risk of stroke after TIAs and of stroke recurrence after a first episode. Our aim is to describe our experience in treating symptomatic carotid stenosis in an emergency setting. All patients admitted for acute neurologic deficits to the Stroke Unit from 1/2002 to 9/2008 were considered possible candidates to surgery. Those treated within 36 hrs from positive carotid imaging studies were reviewed. All patients received a brain CT and an ABCD2 or NIHSS score, as appropriate. Surgery was not offered if NIHSS > 22. TIA was defined by deficits lasting < 24 hrs and negative CT for 72 hrs. Stroke was defined by symptoms lasting > 24 hrs or positive CT. Neurologic complications were defined by a worsening NIHSS or new area of brain ischemia at CT. End points were perioperative death / neurological morbidity as per NIHSS. Among 55 patients (40 male, mean age 69±9.8 yrs), 17 were admitted for TIA (3 amaurosis, 8 single TIA, 6 recurrent) with a mean ABCD2 score of 3.2±1.6 at admission; 38 had a stroke (34 minor, 4 stroke in evolution), with a median NIHSS of 3 (IQR 2-7.5); 14 of them had a positive CT. Median time from symptoms to observation was 4 hrs (2-7), from observation to surgery 34 hrs (9-115), with no difference between TIAs and strokes. We performed 54 endarterectomies (37 patch, 14 direct, 3 eversion) and 1 embolectomy. Local or regional anesthesia was used in 20 patients and general in 35. Among TIAs 1 patient died of an MI and 2 patients suffered a TIA postoperatively. In the stroke group 1 patient died of a cerebral hemorrhage arisen on 4th postop day, being symptoms free until then. 2 patients had a TIA (1 arm weakness and 1 amaurosis). 3 patients experienced a worsening NIHSS: 2 had a stroke while the third had a hyperperfusion syndrome (all CTs negative during hospital stay). Median NIHSS at discharge was 2 (1-3). Overall the death/stroke rate was 5.9% for TIA patients and 10.5% for stroke. Early surgery had higher perioperative mortality and stroke rates than expected. This can probably be acceptable for TIAs if compared to their risk of stroke. Stroke patients most likely need a better selection in order to pick up those who can benefit from early treatment.

Reproducibility and clinical relevance of quantitative EEG parameters in cerebral ischemia: A basic approach

To investigate reproducibility and clinical relevance of quantitative EEG parameters in ischemic cerebrovascular disease. EEG was recorded in 31 patients suffering from subacute ischemic cerebrovascular disease. Ten age-matched control subjects were included as a reference group. Intra-recording, intrarater and interrater reproducibility was calculated for standard EEG measures and for a pair wise derived Brain Symmetry Index (pdBSI). Correlations between EEG parameters, clinical status and volume of ischemia on diffusion weighted imaging (DWI) were calculated. pdBSI was sensitive to asymmetry in the amplitude and frequency domain in a random white noise model and in a simulated sinusoidal model. Minimal Cronbach alpha for intra-recording, intra- and inter-rater reproducibility ranged between 0.95 and 0.99 for standard spectral parameters and between 0.96 and 0.99 for pdBSI. We found a significant difference in pdBSI between stroke patients and control or TIA (p=0.0003). pdBSI correlated significantly with NIH stroke scale at admission and DWI volume across different levels of stroke probability (Spearman's rho=0.64-0.70 and 0.79-0.84, respectively, p<0.00001 for both). pdBSI displays high multilevel reproducibility and reliably discriminates between stroke and TIA patients or control subjects, and correlates significantly with clinical and radiological status. Based on this methodological analysis, reliable EEG parameters can be evaluated in a general stroke population for clinically relevant state and outcome measures.

The California, ABCD, and Unified ABCD2 Risk Scores and the Presence of Acute Ischemic Lesions on Diffusion-Weighted Imaging in TIA Patients

Some clinical models, like California ABCD and unified ABCD2 scores, are now available to predict the early risk of stroke after a TIA. Despite the transitivity of symptoms, DWI identified an area of acute brain ischemia in almost half of patients. It would be interesting to know how the presence of DWI abnormalities relates to clinical risk scores to plan other prognostic variables or to recommend the performance of DWI. We prospectively studied 135 consecutive TIA patients visited by the neurologists in our institution. All patients underwent DWI (3.8+/-1.7 days after symptoms onset). Clinical risk scores (California, ABCD, and ABCD2) were calculated prospectively for each patient. The identification of acute ischemic lesions (positive DWI) was related to the presence of clinical features and clinical risk scores. DWI were positive in 67 (49.6%) patients. After Bonferroni adjustment, elevated ABCD, ABCD2, and California scores were not associated with a positive DWI. However, some clinical symptoms such as facial palsy and motor weakness were associated with a positive DWI (P<0.001). The logistic regression model identified only facial palsy as an independent predictor of acute ischemic lesions (odds ratio 6.26, 95% CI 2.49 to 15.71, P<0.001). Clinical symptoms such as motor impairment, but not clinical risk scores, were associated with a positive DWI. Performing a DWI may add prognostic information to clinical risk scales as a predictor of stroke recurrence after TIA in future large studies.

Dimethylarginine Levels in Cerebrospinal Fluid of Hyperacute Ischemic Stroke Patients are Associated with Stroke Severity

We hypothesise that asymmetric and symmetric dimethylarginine (ADMA, SDMA) are released in cerebrospinal fluid (CSF) due to ischemia-induced proteolysis and that CSF dimethylarginines are related to stroke severity. ADMA and SDMA were measured in CSF of 88 patients with ischemic stroke or TIA within 24 h after stroke onset (mean 8.6 h) and in 24 controls. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission. Outcome was evaluated by institutionalization due to stroke and the modified Rankin scale. Dimethylarginine levels were higher in patients with stroke than in TIA patients, who had higher levels than controls and correlated with the NIHSS. Logistic regression analysis confirmed that dimethylarginines were independently associated with stroke severity. The SDMA/ADMA ratio did not differ significantly between controls and stroke patients. CSF dimethylarginine levels are increased in hyperacute ischemic stroke and are associated with stroke severity.

A neuropsychological study of 12 patients with transient ischemic attacks before and after EC/IC bypass surgery.

A neuropsychological study of 12 patients with transient ischemic attacks from the carotid artery territory was carried out about 2 months following their latest attack, about a week before STA/MCA bypass operation, and again 3 months postoperatively. The results suggest that the TIA patients as a group were slightly intellectually impaired preoperatively. After the operation, a minor neuropsychological improvement had taken place although they still were not fully intellectually rehabilitated.

Secondary Stroke Prevention, and the Role of Antiplatelet Therapies

This review considers treatments of proved efficacy in secondary stroke prevention, with an emphasis on antiplatelet therapy. Most strokes could be prevented, if readily available lifestyle and risk factor modifications could be applied to everyone. In secondary stroke prevention, the same lifestyle and risk factor modifications are also important, along with anticoagulation for patients with cardiac sources of embolus, carotid procedures for patients with significant internal carotid artery stenosis, and antiplatelet therapy. For patients with noncardioembolic ischemic strokes, FDA-approved antiplatelet agents are recommended and preferred over anticoagulants. ASA, clopidogrel, and ASA + ER-DP are recognized as accepted first-line options for secondary prevention of noncardioembolic ischemic stroke. Combined antiplatelet therapy with ASA + clopidogrel has not been shown to carry benefit greater than risk in stroke or TIA patients. Aspirin and extended release dipyridamole appeared to carry a greater benefit over aspirin alone in individual studies, leading to a recommendation of this agent in the AHA guidelines, but the recently completed PRoFESS trial showed no difference in efficacy between clopidogrel and aspirin with extended release dipyridamole, and clopidogrel had better tolerability and reduced bleeding risk.

The clinical significance of diffusion-weighted MR imaging in stroke and TIA patients.

Diffusion-weighted magnetic resonance imaging (DWI) is an advanced imaging technique that allows non-invasive evaluation of water diffusibility in brain tissue. The following report focuses on the clinical significance of DWI in stroke and TIA patients (1) TIA patients demonstrate DWI lesions at a rate of 1 in 6 to 2 in 3. Symptom duration, speech or motor symptoms and aetiology seem to correlate with the rate of DWI positivity. (2) In stroke patients, the DWI detection rate of ischaemic lesions is >95%. Small lesion size and location in the brainstem increase the risk of false-negative DW-images. A negative DW-image in a patient with stroke-like symptoms should stimulate the search for an alternative diagnosis. However, one half of such patients can be expected to have ischaemic stroke as the best final diagnosis. (3) Infarct age determination based on DWI characteristics is not possible in the first few hours. However, the combined interpretation of DWI-images and apparent diffusion coefficient (ADC) maps enables the distinction of infarcts ?5 day old from infarcts >10 days old. On average in DW-images alone, the hyperintense signal disappears after two months. Normalisation can occur as early as one month and as late as four and a half months. (4) DWI lesion size is a prognostic marker of stroke outcome. However, in a mixed stroke population, outcome prediction by DWI cannot replace clinical outcome scores. (5) The mismatch concept hypothesises that DWI lesions reflect irreversibly infarcted tissue that is surrounded by an area of reduced perfusion. The larger the perfusion-diffusion mismatch the more tissue is potentially salvageable, e.g., by early reperfusion. Although this concept is appealing, more recent data have shown that DWI lesions are not necessarily irreversibly damaged tissue and that perfusion abnormalities tend to overestimate the ischaemic penumbra. More recently, the mismatch between clinical stroke severity as measured with the NIH-stroke Scale Score (NIHSSS) and the volume of DWI lesions has been introduced. (6) In posterior circulation stroke, DWI lesion detection rate is significantly lower than in anterior circulation stroke. (7) DWI features provide important information about stroke aetiology. Multiple DWI lesions in more than one circulation suggest cardioembolism. However, this assignment should be restricted to DWI lesions showing the same appearance on ADC-maps. In patients with lacunar syndromes, every fourth to sixth patient can be expected to have >1 DWI lesion, indicating an embolic mechanism. Thus, DWI findings may be clinically useful to tailor the aetiological work-up, which may result in early implementation of specific treatment for secondary stroke prevention. (8) DWI may detect clinically silent ischaemic lesions after carotid interventions. A systematic review reported the rate of new DWI lesions as being significantly higher in carotid stenting patients (37%) compared to carotid endarterectomy patients (10%). As caveats, all studies included were non randomized trials. In addition, the clinical significance of these lesions is unclear. Studies, comparing the risk of silent ischaemia in carotid stenting versus endarterectomy patients and evaluating the value of DWI as surrogate marker in a randomised, prospective setting are currently under way. DWI provides clinically useful information and has the means to improve the quality of diagnosis, treatment, and outcome prediction in stroke and TIA patients.

The clinical significance of diffusion-weighted MR imaging in stroke and TIA patients.

Diffusion-weighted magnetic resonance imaging (DWI) is an advanced imaging technique that allows non-invasive evaluation of water diffusibility in brain tissue. The following report focuses on the clinical significance of DWI in stroke and TIA patients (1) TIA patients demonstrate DWI lesions at a rate of 1 in 6 to 2 in 3. Symptom duration, speech or motor symptoms and aetiology seem to correlate with the rate of DWI positivity. (2) In stroke patients, the DWI detection rate of ischaemic lesions is >95%. Small lesion size and location in the brainstem increase the risk of false-negative DW-images. A negative DW-image in a patient with stroke-like symptoms should stimulate the search for an alternative diagnosis. However, one half of such patients can be expected to have ischaemic stroke as the best final diagnosis. (3) Infarct age determination based on DWI characteristics is not possible in the first few hours. However, the combined interpretation of DWI-images and apparent diffusion coefficient (ADC) maps enables the distinction of infarcts ?5 day old from infarcts >10 days old. On average in DW-images alone, the hyperintense signal disappears after two months. Normalisation can occur as early as one month and as late as four and a half months. (4) DWI lesion size is a prognostic marker of stroke outcome. However, in a mixed stroke population, outcome prediction by DWI cannot replace clinical outcome scores. (5) The mismatch concept hypothesises that DWI lesions reflect irreversibly infarcted tissue that is surrounded by an area of reduced perfusion. The larger the perfusion-diffusion mismatch the more tissue is potentially salvageable, e.g., by early reperfusion. Although this concept is appealing, more recent data have shown that DWI lesions are not necessarily irreversibly damaged tissue and that perfusion abnormalities tend to overestimate the ischaemic penumbra. More recently, the mismatch between clinical stroke severity as measured with the NIH-stroke Scale Score (NIHSSS) and the volume of DWI lesions has been introduced. (6) In posterior circulation stroke, DWI lesion detection rate is significantly lower than in anterior circulation stroke. (7) DWI features provide important information about stroke aetiology. Multiple DWI lesions in more than one circulation suggest cardioembolism. However, this assignment should be restricted to DWI lesions showing the same appearance on ADC-maps. In patients with lacunar syndromes, every fourth to sixth patient can be expected to have >1 DWI lesion, indicating an embolic mechanism. Thus, DWI findings may be clinically useful to tailor the aetiological work-up, which may result in early implementation of specific treatment for secondary stroke prevention. (8) DWI may detect clinically silent ischaemic lesions after carotid interventions. A systematic review reported the rate of new DWI lesions as being significantly higher in carotid stenting patients (37%) compared to carotid endarterectomy patients (10%). As caveats, all studies included were non randomized trials. In addition, the clinical significance of these lesions is unclear. Studies, comparing the risk of silent ischaemia in carotid stenting versus endarterectomy patients and evaluating the value of DWI as surrogate marker in a randomised, prospective setting are currently under way. DWI provides clinically useful information and has the means to improve the quality of diagnosis, treatment, and outcome prediction in stroke and TIA patients.

A survey on cerebral infarction/transient ischemic attack inpatients compliance with secondary stroke prevention and follow-up 90 days

Poor compliance with evidence-based-medicine guidelines could significantly influence the effect of stroke prevention strategies. The objectives of this survey are to investigate the current status in Beijing of cerebral infarction/TIA (transient ischemic attack) inpatients' adherence to the evidence-based-medicine secondary prevention and behavior modifications both at the discharge and at 90-day follow up. The survey included cerebral infarction/TIA patients successively admitted from 1, Oct 2006 to 1, May 2007, used ACEI/ARB, Statin, anti-platelet agents therapy, accepted carotid endarterctomy or angioplasty or stent, and modified behaviors to stop smoking and control weight. Data of patients during hospitalization were obtained from the medical documents in the inpatient department of 7 centers. The detailed information included the medicine therapy, lifestyle modifications, patients' social demographic background (age, sex, education and way of payment), major risk factors for stroke, and ischemic event subtypes (TIA or cerebral infarction). Above information of part of patients were collected through telephone interview at 90-day follow-up if the patients were not able to visit the clinic. 708 cerebral infarction/TIA inpatients who didn't have contraindications were included. Among them, the patents who haven't used anti-platelet agents, nor taken statin, nor accepted ACEI/ARB were about 0.4%, 41.8% and 63.6% respectively. Neither 27% of the patients have accepted the instructions on stop smoking. While about 588 patients suitable to drug therapy were followed up at 90 days, but the percentage of these patients who haven't compliance on anti-platelet agents, statin, ACEI/ARB was 26.9%, 52.6% and 59.4% respectively. Only 66.9% of the smoking patients have received the doctor instructions on smoking cessation. Stroke recurrence rate in China is higher than that of average figures in western countries. One of the key reasons of high recurrence of stroke in China is the poor adherence to stroke secondary prevention guidelines. Thus, investigate current status of secondary prevention among hospitals in capital of China and promote strategies to enhance the adherence to the guidelines and fill the gap between the clinical practice and evidence-based medicine in China, which is able to lower the stroke recurrence and save lives are urgently needed. Physician should take great care of the patient's compliances on the evidenced-based-medicine secondary prevents and behavior modifications, and take effective measures to improve the compliances.

Secondary Prevention in a Large Stroke Population

In this study, linked, anonymous data from The National Hospital Discharge Register and the Swedish Prescribed Drug Register were used for studying to what extent recommended drugs for secondary prevention after stroke and TIA were purchased by patients in the region of Stockholm, Sweden (2 million inhabitants). Data on purchased drugs for secondary stroke prevention during July 2005 to June 2006 by 17 902 patients >18 years discharged after stroke or TIA during the period 1997 to June 2005 were analyzed by age, gender, and year of discharge. Antiplatelets and warfarin were purchased by 87% of all stroke and 83% of all TIA patients, antihypertensives by 74% and 70%, and lipid lowering drugs by 41% and 39%, respectively. Time after discharge had only a minor influence on the proportion of patients purchasing the medicines.

Evaluation of lactate as a marker of metabolic stress and cause of secondary damage in acute ischemic stroke or TIA

Background Accumulation of lactate in ischemic regions has been documented in acute stroke. We evaluated the relation between lactate levels in blood and cerebrospinal fluid (CSF) and ischemic stroke evolution and outcome. Methods Lactate was measured in blood of 187 acute ischemic stroke and TIA patients at admission, 24 h, 72 h and 7 days after stroke onset. In a subpopulation of 85 stroke patients and in 51 controls, lactate was measured in CSF. Stroke evolution was evaluated by change in the NIHSS score within the first 72 h and by occurrence of progressing stroke. At 3 months after stroke, outcome was assessed on the basis of mortality rate and the modified Rankin Scale. Results We found no relation between lactate levels in blood and stroke evolution or outcome. Lactate in CSF was higher in stroke patients than in controls and correlated with stroke evolution and outcome. Multivariate regression analyses showed that CSF lactate levels, age and stroke severity are independent predictors for stroke evolution and outcome. Conclusions Lactate levels in CSF, but not in blood, are a reliable marker for metabolic crisis in acute ischemic stroke and correlate with the stroke evolution in the subacute phase and with long-term outcome.

Outcomes of patients with transient ischaemic attack after hospital admission or discharge from the emergency department

To compare outcomes at 28 days and 1 year between patients admitted to hospital and those discharged after presenting to the emergency department (ED) with transient ischaemic attack (TIA). All TIA presentations to EDs in a large metropolitan and rural region of Sydney and its surroundings, New South Wales, between 2001 and 2005 were extracted from state health department databases and followed up over 1 year. Admission and discharge data and subsequent TIA or stroke presentations were identified. TIA recurrence or stroke. Of 2535 presentations to an ED with TIA during the 5-year period, 1816 patients were admitted to hospital (71.6%) and 719 were discharged from the ED (28.4%). At 28 days, the discharged group had significantly higher rates of recurrence than the admitted group for all events (TIA or stroke) (5.3% v 2.3%, P < 0.001), stroke (2.1% v 0.7%, P = 0.002), and recurrent TIA (3.2% v 1.6%, P = 0.01). During the 29-365-day follow-up period, there was no significant difference between the discharged and admitted groups for all events (4.2% v 5.1%; P = 0.37), stroke (1.3% v 2.5%; P = 0.06) or recurrent TIA (2.9% v 2.6%; P = 0.65). Patients with an ED diagnosis of TIA may benefit from admission to hospital through a reduced risk of early stroke.

Reversible diffusion-weighted lesion in a TIA patient without arterial recanalization: A case report

A 70-year-old man with right hemiparesis (NIHSS score 15) was admitted to our hospital 1 h after onset. Diffusion-weighted imaging (DWI) revealed a hyperintense lesion in the left corona radiata and magnetic resonance angiography (MRA) revealed occlusion of the left middle cerebral artery (MCA). At 2.5 h after onset, his neurological deficits dramatically improved (with NIHSS score change from 15 to 2). Immediately thereafter, follow-up MRI revealed that the hyperintense lesion on DWI had disappeared, though the left MCA occlusion remained. By the end of follow-up MRI examination, his neurological deficits had completely disappeared. We report here the patient with transient ischemic attack with a reversible ischemic lesion on DWI without early arterial recanalization.

Countable and non-countable microembolic signals by TCD in first-ever stroke or TIA patients with PFO

There are data in the literature indicating that the number of microembolic signals (MES) in patients with patent foramen ovale (PFO) is directly related to stroke incidence and recurrence. We thus hypothesized that the amount of artificially induced microembolic signals monitored by contrast transcranial Doppler (cTCD) would be greater in younger patients with PFO and stroke (when cryptogenic strokes related to the PFO are frequent). The final analysis included 109 patients with first-ever ischemic stroke or TIA with PFO, as detected by Transesophageal Echocardiography (TEE), and MES, as measured by cTCD. Thirty-seven patients (aged 19-45 years) were defined as the "younger" group, and the other 72 patients (aged 46-77 years) were defined as the "older" group. Eighty-six patients (78.9%) suffered from stroke, including 28 in the younger group and 58 in the older group. The pattern of microembolization was defined as "countable" when the observers were able to calculate the number of MES. In the case of a "shower" of MES on TCD examination, the pattern of monitoring was defined as "non-countable." Ischemic heart disease, and hyperlipidemia were found to be significantly more frequent in the group of older patients. Twenty-three patients (62.2%) in the younger group had cryptogenic stroke or TIA (no risk factors found), as compared to 26 patients (36.1%) in the older group (p=0.009). There were 23 patients with a non-countable pattern of MES in the older group, as compared with 5 such patients in the younger group (p=0.04). There was no difference found in the number of MES between the groups in those patients with a countable pattern of MES (13.3+/-11.8 in the younger group vs. 13.7+/-11.7 in the older group). In stroke and TIA patients above 45 years of age, PFOs producing a large amount of MES on TCD examination are frequent. Thus, there is no correlation between a large amount of MES and stroke or TIA in young patients.

Vertebral artery dissection complicated by basilar artery occlusion successfully treated with intra-arterial thrombolysis: three case reports

Cervical artery dissection is an important cause of stroke in young patients and accounts of 10%-20% of stroke or TIA in patients aged less than 50 years. Basilar artery occlusion (BAO) is an infrequent cause of acute stroke, which invariably leads to death or long-term disability if not recanalized. We describe three patients with BAO caused by vertebral dissection, successfully treated with intra-arterial thrombolysis. The lysis of the occluding embolus was obtained by injection of the thrombolytic drug directly or near the thrombus without haemorrhagic complications. Our cases confirm the safety and efficacy of intra-arterial thrombolysis in patients with BAO due to a vertebral artery dissection.

The investigation analysis on the cerebral infarction recognition of TIA patients

目的 探讨TIA患者对脑梗死(CI)防治知识的认知度状况及教育效果评价.方法 采用自行设计的问卷调查评价表,对120例TIA病人进行调查、评价.结果 77%～81.7%的患者缺乏对TIA与CI的相关知识,40%～61.8%的患者对导致CI的危险因素缺乏了解,45%～55%的患者缺乏有关不良生活习惯的知识,69.2%的患者缺乏需要长期服药物及药物副作用观察方面的知识,43.3%～62.5%的患者缺乏TIA的保健常识.结论 TIA患者对CI防治知识的认知度低,导致TIA患者最后发展成为CI的危险性明显提高.提示我们在临床工作中,脑血管疾病防治知识的宣教与临床护理同等重要。

Abstract 2921: Genome-wide Association Reveals Sequence Variants on 4q25 that Affect the Risk of Atrial Fibrillation and Stroke

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over eighty, causes significant morbidity, and is an independent predictor of mortality. We have carried out a genome-wide scan using 316,000 SNPs on an Illumina beadchip to genotype a large atrial fibrillation cohort in Iceland. We found two common sequence variants (SNPs) within the same LD block on chromosome 4q25 near the PITX2 gene which increase the risk of AF substantially (by 1.72 and 1.39 per copy, respectively). An even higher risk was observed in individuals with typical atrial flutter. The association was replicated in Swedish, American, and Chinese populations. These variants do not associate with known risk factors for AF and thus provide an independent predictor of risk. The variants have a stronger effect in individuals younger than 80 but the risk in males and females is indistinguishable. As expected, given that AF is the primary cause of cardiogenic stroke, we found significant correlation to cardiogenic stroke in multiple cohorts. We have now followed up this initial study by combining these two variants to define a test to predict the risk of AF and show its characteristics in a meta-analysis of about 4500 AF patients from four European and American Caucasian cohorts. We demonstrate the effect of age on prediction. About 30% of the general population is positive for this test and has an OR of 1.8 for atrial fibrillation in individuals younger than 80. Such a test may be useful in recently diagnosed ischemic stroke and TIA patients to help decide which patients may benefit from ambulatory cardiac monitoring and perhaps provide a higher yield of detection of asymptomatic intermittent AF that is not discovered during the standard 24 to 48 hour monitoring within the hospital. This may be particularly important given that secondary stroke prevention strategies of antiplatelet agents and statins widely used for atherosclerosis-related strokes are much less effective for preventing strokes caused by AF.

Diffusion weighted MRI imaging and MES detection in the assessment of stroke origin

Objectives: This study compares the additional benefit of diffusion-weighted MRI (DWI) and microembolus detection by transcranial Doppler ultrasonography (TCD) in the assessment of stroke etiology.Methods: Fifty-five acute anterior circulation stroke or TIA patients were investigated by both cranial DWI and bilateral TCD of the middle cerebral arteries (1 hour).Results: In one of the 13 patients without acute ischemic lesions visualized on DWI, microembolic signal (MES) detection was positive. However, in 33 out of 44 patients without MES, DWI revealed at least one lesion. In two patients with unilateral territorial infarction and otherwise normal cardiovascular work-up, bilateral MES were found thus localizing the embolic source into the aortic arch or the heart. In a further patient with a dissection, the occurrence of contralateral MES raised doubts on a dissection to be the cause of the infarct.Discussion: There is a contribution of both techniques to the understanding of stroke etiology. The impact of DWI is, however, superior to that of MES detection. Longer TCD recording times may diminish this discrepancy.

Performance of the ABCD and ABCD2 Scores in TIA Patients with Carotid Stenosis and Atrial Fibrillation

Background: It has been suggested that scores for risk stratification of TIA patients might not identify patients with carotid stenosis or atrial fibrillation (AF) and that this might undermine the usefulness of such scores. Methods: In patients with TIA in the Oxford Vascular Study, we studied the associations between ABCD and ABCD2 scores, the presence of ≧50% ipsilateral carotid stenosis or AF, and the risk of stroke at 7 days. Results: Among 285 TIA patients (from 559 referrals of possible TIA), 69 (24.2%) had either ≧50% carotid stenosis (n = 29) or AF (n = 42), or both (n = 2). Although the ABCD and ABCD2 scores were highly predictive of stroke at 7 days (p < 0.0001), there was no clear relationship between either score and the prevalence of ≧50% carotid stenosis or AF. However, the scores did predict the 7-day stroke risk in patients with these pathologies: ABCD score (trend – p = 0.05); ABCD2 (trend – p = 0.03). Five of the 6 patients with AF or symptomatic stenosis who had a stroke within 7 days of their TIA had an ABCD score of ≧5 and all 6 had an ABCD2 score of ≧4. Conclusions: The ABCD and ABCD2 risk scores appear to identify patients with ≧50% carotid stenosis or AF who are at high risk of stroke. However, these findings should be interpreted with caution due to the small number of outcomes among these subgroups, and further validations are necessary.