Dual Testing to Achieve Low On-treatment Platelet Reactivity for Aneurysm Embolization.

BACKGROUND AND PURPOSE: Although point-of-care tests are used extensively to test platelet function before endovascular aneurysm treatment, their use and validity are still debated. We compared the results of two point-of-care tests (VerifyNow® and Multiplate®) for assessing patients treated with stents and flow diverters and determined their relation to periprocedural complications. METHODS: All patients undergoing treatment of intracranial aneurysms were tested using both methods and were retrospectively evaluated. Patients with acute subarachnoid hemorrhage and those who had to be maintained on anticoagulants for unrelated diseases were excluded. An acceptable level of platelet inhibition was required on both tests to commence with treatment, otherwise antiplatelet medication was adjusted to reach this level. RESULTS: Mean PRU (platelet reactivity units) and ADP AUC (adenosine diphosphate area under the aggregation curve) were 68 ± 66 and 23 ± 15, respectively, in 295 patients. Both tests showed a good correlation (r = 0.45). Both tests were able to predict hemorrhagic events but not ischemic events. When patients with very low reactivity (PRU < 60) were compared to the rest of the group, there were more hemorrhagic events in the first group but the overall rate of complications were similar (p = 0.27). CONCLUSION: In this largest study comparing two widely used commercial platelet function tests, the correlation between the tests were less than ideal; however, the very low platelet reactivity attained by the help of dual platelet testing did not result in an increased overall complication rate.

Post-stroke inflammatory response is linked to volume loss in the contralateral hemisphere.

OBJECTIVES: There is a delicate homeostatic balance between the central nervous system and immune system. Stroke triggers an immunodepressive state to suppress a potential immune reaction directed against neuroglial tissue; however, this supposedly protective response inadvertently results in an infection-prone, and thereby a pro-inflammatory setting. In this study, we assessed the magnitude of cerebral volume loss in the unaffected contralateral hemisphere following stroke, and determined its relationship with inflammatory cascades. METHODS: The volume of the hemisphere contralateral to the ischemic insult was measured on admission and follow-up MRI's in 50 ischemic stroke patients. Information related to clinical features, infectious complications, and markers of inflammation (erythrocyte sedimentation rate, neutrophil/lymphocyte ratio, C-reactive protein) were prospectively collected, and their relationship with hemispheric volume change was evaluated using bivariate and multivariate statistics. RESULTS: The contralateral hemisphere volume decreased by a median (interquartile range) of 14 (4-32) mL after a follow-up duration of 101 (63-123) days (p < .001); the volume reduction was 0.8 (0.2-1.8) % per month with respect to baseline. Old age, atrial fibrillation, stroke severity, C-reactive protein level, neutrophil/lymphocyte ratio, and development of infections during hospitalization were significantly associated with volume loss (p < .05). Stroke severity (NIHSS score or infarct volume) and inflammation related parameters (neutrophil/lymphocyte ratio or systemic infections) remained independently and positively associated with volume loss in multivariate regression models. CONCLUSIONS: Cerebral tissue changes following stroke are not limited to the ischemic hemisphere. Apart from stroke severity, a pro-inflammatory state and post-stroke infections contribute to cerebral volume loss in the non-ischemic hemisphere.

Emergence of colistin and carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (CCR-Acb) complex in a neurological intensive care unit followed by successful control of the outbreak.

BACKGROUND: Colistin and carbapenem-resistant Acinetobacter calcoaceticus- Acinetobacter baumannii complex (CCR-Acb complex) was isolated from two consecutive patients in the neurological intensive care unit (NICU). An urgent reaction to this desperate situation was required. PATIENTS AND METHODS: Screening cultures were taken from the other patients sharing the NICU with index patients and repeated periodically. NICU was closed for new admissions. Infection control precautions (ICP) such as hand hygiene, cohorting patients colonized with CCR-Acb complex, cohorting the staff caring for these patients, daily bathing with chlorhexidine gluconate impregnated clothes, using gowns when contacting with patients and patient care area, and sodium hypochlorite tablets for environmental cleaning were enforced. RESULTS: Screening cultures revealed carbapenem-resistant Acb complex in 12 out of 32 patients and 8 of them were colonized with CCR-Acb complex. NICU was opened for new admissions one month later. No further new cases with CCR-Acb complex were detected by screening cultures after 6 weeks with enforcement of ICP. Moreover, the rate of nosocomial infections caused by other multi-drug resistant Gram-negative bacilli (MDR-GNB) decreased significantly when rates before and after closing the NICU were compared. CONCLUSION: ICP were effective not only to limit the spread of CCR-Acb complex but also decreased the incidence of other MDR-GNB infections when applied adequately.

The effect of carotid artery stenting on capillary transit time heterogeneity in patients with carotid artery stenosis.

INTRODUCTION: Carotid revascularisation improves haemodynamic compromise in cerebral circulation as an additional benefit to the primary goal of reducing future thromboembolic risk. We determined the effect of carotid artery stenting on cerebral perfusion and oxygenation using a perfusion-weighted MRI algorithm that is based on assessment of capillary transit-time heterogeneity together with other perfusion and metabolism-related metrics. PATIENTS AND METHODS: A consecutive series of 33 patients were evaluated by dynamic susceptibility contrast perfusion-weighted MRI prior to and within 24 h of the endovascular procedure. The level of relative change induced by stenting, and relationship of these changes with respect to baseline stenosis degree were analysed. RESULTS: Stenting led to significant increase in cerebral blood flow (p < 0.001), and decrease in cerebral blood volume (p = 0.001) and mean transit time (p < 0.001); this was accompanied by reduction in oxygen extraction fraction (p < 0.001) and capillary transit-time heterogeneity (p < 0.001), but an overall increase in relative capillary transit-time heterogeneity (RTH: CTH divided by MTT; p = 0.008). No significant change was observed with respect to cerebral metabolic rate of oxygen. The median volume of tissue with MTT > 2s decreased from 24 ml to 12 ml (p = 0.009), with CTH > 2s from 29 ml to 19 ml (p = 0.041), and with RTH < 0.9 from 61 ml to 39 ml (p = 0.037) following stenting. These changes were correlated with the baseline degree of stenosis.Discussion: Stenting improved the moderate stage of haemodynamic compromise at baseline in our cohort. The decreased relative transit-time heterogeneity, which increases following stenting, is probably a reflection of decreased functional capillary density secondary to chronic hypoperfusion induced by the proximal stenosis.Conclusion: Carotid artery stenting, is not only important for prophylaxis of future vascular events, but also is critical for restoration of microvascular function in the cerebral tissue.

Antithrombotic treatment at onset of stroke with atrial fibrillation, functional outcome, and fatality: a systematic review and meta-analysis.

BACKGROUND: In atrial fibrillation-associated stroke, conflicting data exist regarding association between therapeutic vitamin K-antagonist anticoagulation (International Normalized Ratio 2-3) and early death and functional outcome, and few data exist relating to late outcome in ischemic and haemorrhagic atrial fibrillation-stroke. AIM: We performed a systematic review and meta-analysis of oral anticoagulation at stroke onset, death and functional outcome. METHODS: We performed a systematic review, searching multiple sources. Studies were included if outcomes in atrial fibrillation-associated stroke were reported stratified by pre-stroke antithrombotic status, with documented International Normalized Ratio at onset. Outcomes were survival and good functional outcome (modified Rankin score 0-2) at discharge/30 days, and at one-year. RESULTS: Of eight studies (3552 patients) in ischemic stroke, International Normalized Ratio ≥ 2 compared with other treatments (International Normalized Ratio < 2, antiplatelet, or no antithrombotic) was associated with good outcome [pooled odds ratio 1·9 (95% confidence interval) 1·5-2·5, P < 0·001] and improved survival at 30 days discharge (pooled odds ratio for death 0·4, confidence interval 0·2-0·5, P < 0·001). The net benefit remained after inclusion of haemorrhagic stroke (odds ratio for good outcome 1·89, confidence interval 1·45-2·46, P < 0·001). At one-year, improved functional outcome for International Normalized Ratio ≥ 2 (pooled odds ratio 1·7, confidence interval 1·0-2·7, P = 0·04) and survival (odds ratio for death 0·5, confidence interval 0·4-0·8, P = 0·001) were also observed. CONCLUSIONS: Therapeutic International Normalized Ratio at stroke onset was associated with early and late improved survival and functional recovery suggesting sustained benefit for warfarin anticoagulation for stroke outcome in atrial fibrillation patients. Long-term outcome data following stroke in patients taking new oral anticoagulants is required.

Ischemic stroke phenotype in patients with nonsustained atrial fibrillation.

BACKGROUND AND PURPOSE: The widespread use of ambulatory cardiac monitoring has not only increased the detection of high-risk arrhythmias like persistent and paroxysmal atrial fibrillation (AF), but also made it possible to identify other aberrations such as short-lasting (<30 seconds) irregular runs of supraventricular tachycardia. Ischemic stroke phenotype might be helpful in understanding whether these nonsustained episodes play a similar role in stroke pathophysiology like their persistent and paroxysmal counterparts. METHODS: In a consecutive series of patients with ischemic stroke, we retrospectively determined clinical and imaging features associated with nonsustained AF (n=126), defined as <30-second-lasting supraventricular tachyarrhythmias with irregular RR interval on 24-hour Holter monitoring, and compared them to patients with persistent/paroxysmal AF (n=239) and no AF (n=246). RESULTS: Patients with persistent/paroxysmal AF significantly differed from patients with nonsustained AF by a higher prevalence of female sex (odds ratio [95% confidence interval], 1.8 [1.1-2.9]), coronary artery disease (1.9 [1.1-3.0]), and embolic imaging features (2.7 [1.1-6.5]), and lower frequency of smoking (0.4 [0.2-0.8]) and hyperlipidemia (0.5 [0.3-0.8]). In contrast, patients with no AF were younger (0.5 [0.4-0.6] per decade) and more likely to be male (1.7 [1.0-2.8]) in comparison with nonsustained AF population. The prevalence of nonsustained AF was similar among cryptogenic and noncryptogenic stroke patients (32% versus 29%). Voxel-wise comparison of lesion probability maps revealed no significant difference between cryptogenic stroke patients with and without nonsustained AF. CONCLUSIONS: Clinical features of patients with nonsustained AF exhibited an intermediary phenotype in between patients with persistent/paroxysmal AF and no AF. Furthermore, imaging features did not entirely resemble patterns observed in patients with longer durations of AF.

Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment.

BACKGROUND AND PURPOSE: Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. METHODS: We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. RESULTS: In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). CONCLUSIONS: In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.

Concurrent occurrence of human and equine West Nile virus infections in Central Anatolia, Turkey: the first evidence for circulation of lineage 1 viruses.

BACKGROUND: West Nile fever is an important zoonotic infection caused by West Nile virus (WNV), a member of the Flaviviridae. Previous serological data from Turkey suggest widespread WNV circulation. This report includes cases of human and equine WNV infections occurring concurrently, and manifesting as central nervous system infections, in two neighboring provinces of Central Anatolia, Turkey. A partial phylogenetic analysis of the causative virus is given for the first time. METHODS: The cases were reported in February (horses) and March (human). Symptoms of the disease were similar in the two species, characterized by neurological manifestations suggesting meningoencephalitis. Real-time/nested PCRs and commercial immunoassays and a plaque reduction neutralization assay were employed for the detection of viral RNA and specific antibodies, respectively. RESULTS: WNV RNAs were detected in buffy coat (horses) and cerebrospinal fluid (human) samples. Partial nucleotide sequences of the E-gene coding region revealed that the strains are closely related to viruses of lineage 1, clade 1a. Accompanying equine serosurveillance demonstrated WNV-specific antibodies in 31.6% of the samples. CONCLUSIONS: This is the first report of acute WNV infections caused by lineage 1 strains from Turkey, in concordance with previous reports from some European and North African countries.

[A case of central nervous system infection due to west nile virus lineage-1 in ankara province, Turkey]. / Ankara Ilinde Bati Nil Virusu Köken-1 Kaynakli Bir Merkezi Sinir Sistemi Enfeksiyonu Olgusu.

West Nile virus (WNV) is a mosquito-borne Flavivirus (family Flaviviridae), maintained in an enzootic cycle between birds as amplifying hosts and mosquito vectors. While WNV exposure in humans frequently remain subclinical, a febrile illness called West Nile fever occurs in about 20% and neuroinvasive disease in less than 1% of the affected individuals. For the last two decades, WNV has caused outbreaks of severe neuroinvasive disease in humans and horses in Europe, the Mediterranean Basin and emerged in the American continent. Although, previous serosurveillance reports have revealed human WNV exposure in various regions in Turkey; well-characterized clinical cases have only been reported after 2009-2010. In this report, a case of WNV encephalitis caused by a Lineage 1 virus strain and identified in Ankara province, Central Anatolia, Turkey, was presented. An 87 year-old woman with a history of hypertension and a recent febrile episode was admitted to Hacettepe University Hospital in late May 2012, with altered consciousness, myoclonic jerks in facial muscles and left extremity. Hyponatremia and increased alanine and aspartate aminotransferase levels were noted in blood analyses. Initial electroencephalogram (EEG) demonstrated diffuse slow waves. Areas of restricted diffusion in right dorsal thalamus was observed in cranial magnetic resonance imaging (MRI). Despite supportive therapy, the patient's neurological condition worsened. Follow-up EEG displayed paroxysmal lateralizing epileptiform discharges (PLEDs) in the right hemisphere and T2-hyperintense lesions in the right temporoparietal cortex, insula and thalamus with components of cytotoxic and vasogenic edema were observed in MRI. A cerebrospinal fluid (CSF)-serum pair was evaluated to identify potential causes of encephalitis. CSF biochemical and microscopic findings were within normal limits except for decreased glucose levels. Bacterial, mycobacterial and fungal cultures, antigen assays and polymerase chain reaction (PCR) employed for Herpes simplex virus types 1 and 2 were negative. Commercial and in house assays for WNV, tick-borne encephalitis virus, Toscana virus (TOSV) antibodies revealed TOSV IgG in serum. Previously described nested PCRs targeting WNV envelope glycoprotein and phlebovirus consensus sequences demonstrated WNV positive results in serum and CSF, which were further characterized via cycle sequencing of amplicons as WNV Lineage 1 Clade 1a. Four serum samples obtained within 23 days after the diagnosis were negative for viral RNA and specific antibodies via commercial assays and WNV plaque reduction neutralization assay. During follow-up with supportive therapy and anti-epileptics, the patient's general and neurological condition improved mildly and control EEG and MRI demonstrated regression of previous lesions. However, the patient passed away on the 10th week of hospital admission due to nosocomial infections. These findings confirmed the inital data which indicated the circulation of WNV Lineage 1 strains in Central Anatolia, Turkey. WNV seroconversion may be delayed or absent in elderly individuals without overt diseases associated with immunosuppression. Thus investigation of WNV RNA together with the specific serological tests may help the accurate diagnosis of suspected cases.

Aortic interruption presenting with recurrent ischemic strokes in an adult.

Presentation of an interrupted aortic arch (IAA) in adulthood is extremely rare. Nonhemorrhagic stroke has not been reported previously in any adult with IAA. We, herein, describe a formerly asymptomatic 52-year-old male presenting with recurrent vertebrobasilar circulation ischemic strokes resulting from accelerated atherosclerotic arteriopathy secondary to IAA associated upper body hypertension. Surgical correction of IAA led to treatment of hypertension and cessation of ischemic attacks together with regression of collateral arterial networks as shown by computer tomography angiography.

Addition of brain and carotid imaging to the ABCD² score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study.

BACKGROUND: The ABCD² score improves stratification of patients with transient ischaemic attack by early stroke risk. We aimed to develop two new versions of the score: one that was based on preclinical information and one that was based on imaging and other secondary care assessments. METHODS: We analysed pooled data from patients with clinically defined transient ischaemic attack who were investigated while in secondary care. Items that contribute to the ABCD² score (age, blood pressure, clinical weakness, duration, and diabetes), other clinical variables, carotid stenosis, and abnormal acute diffusion-weighted imaging (DWI) were recorded and were included in multivariate logistic regression analysis of stroke occurrence at early time intervals after onset of transient ischaemic attack. Scores based on the findings of this analysis were validated in patients with transient ischaemic attack from two independent population-based cohorts. FINDINGS: 3886 patients were included in the study: 2654 in the derivation sample and 1232 in the validation sample. We derived the ABCD³ score (range 0-9 points) by assigning 2 points for dual transient ischaemic attack (an earlier transient ischaemic attack within 7 days of the index event). C statistics (which indicate discrimination better than chance at >0·5) for the ABCD³ score were 0·78 at 2 days, 0·80 at 7 days, 0·79 at 28 days, and 0·77 at 90 days, compared with C statistics for the ABCD² score of 0·71 at 2 days (p=0·083), 0·71 at 7 days (p=0·012), 0·71 at 28 days (p=0·021), and 0·69 at 90 days (p=0·018). We included stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points) in the ABCD³-imaging (ABCD³-I) score (0-13 points). C statistics for the ABCD³-I score were 0·90 at 2 days (compared with ABCD² score p=0·035), 0·92 at 7 days (p=0·001), 0·85 at 28 days (p=0·028), and 0·79 at 90 days (p=0·073). The 90-day net reclassification improvement compared with ABCD² was 29·1% for ABCD³ (p=0·0003) and 39·4% for ABCD³-I (p=0·034). In the validation sample, the ABCD³ and ABCD³-I scores predicted early stroke at 7, 28, and 90 days. However, discrimination and net reclassification of patients with early stroke were similar with ABCD³ compared with ABCD². INTERPRETATION: The ABCD³-I score can improve risk stratification after transient ischaemic attack in secondary care settings. However, use of ABCD³ cannot be recommended without further validation. FUNDING: Health Research Board of Ireland, Irish Heart Foundation, and Irish National Lottery.

Unusually prolonged progressing stroke: an expanding anterior cerebral artery infarction.

Progressive clinical deterioration over a period of weeks coupled with MRI evidence of infarction growth is quite uncommon. In this report, we describe a patient with an occluded left anterior cerebral artery (ACA) at the origin of the A2 segment. His symptoms attributable to a posteriorly located small infarction within the ACA territory slowly progressed during the following 8 weeks. A follow-up MRI revealed that the infarction had expanded to involve the whole region of the left ACA. Occasional patients like ours indicate that stroke is a dynamic disorder with an extremely variable clinical course and state of tissue injury.