Cerebral Ischemia In Patients Research Articles

Carotid endarterectomy in patients with symptomatic occlusions of the contralateral internal carotid artery

The main aim of the study was to investigate the effect of carotid endarterectomy on the prognosis of chronic cerebral ischemia in patients with symptomatic occlusions of the contralateral internal carotid artery, assess risks of surgical complications, and substantiate the staged surgical approach for treatment of patients with this pathology. The article analyzes the experience in surgical treatment of 83 patients with symptomatic ICA occlusions who underwent surgery for contralateral carotid artery stenosis. In 40 patients, only carotid endarterectomy (CEA) was performed on the side of hemodynamically significant stenosis (group 1). In 43 (52%) cases, apart from CEA, extracranial-intracranial (EC-IC) bypass was performed at the second stage (23 cases, group 2) or the first stage (19 cases, group 3). A surgical treatment approach was chosen based on clinical symptoms, severity of contralateral carotid artery stenosis, and the magnitude of perfusion deficiency in the territory of carotid occlusion. The conducted analysis revealed that patients with symptomatic occlusions and contralateral carotid artery stenoses represented a heterogeneous group with a different efficacy of carotid endarterectomy and with risks of perioperative complications. As cerebrovascular insufficiency in the territory of carotid occlusion and a related neurological deficit worsen, the risks of complications of contralateral carotid endarterectomy increase, and its clinical efficacy decreases. In these cases, cerebral revascularization on the ICA occlusion side should be performed at the first stage.

Predictors of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage with Asymptomatic Angiographic Vasospasm on Admission

Risk of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) with asymptomatic angiographic vasospasm on admission is unclear in the literature. The goal of this study is to identify predictors of clinical DCI in this group of patients. An exploratory subgroup analysis was conducted in the SAHIT (Subarachnoid Hemorrhage International Trialists) data repository to identify predictors of clinical DCI in patients with good-grade aSAH (World Federation of Neurological Surgeons grade I and II) with angiographic vasospasm on admission. Predictors considered include age, sex, systolic blood pressure at presentation, World Federation of Neurological Surgeon grade, Fisher grade, aneurysm size and location, treatment modality, hydrocephalus requiring external ventricular drain insertion, and severity of vasospasm. The predictors were ranked based on dominance analysis with R2 as fit statistics and assessed in a set of logistic regression analysis models. Four data sets out of 16 studies in the SAHIT database were analyzed, with a total of 4125 patients. One hundred and ninety-one patients (4.6%) had asymptomatic angiographic vasospasm at admission. Of those, 78 patients (40.8%) developed clinical DCI. Univariate analysis showed significant associations between severe vasospasm on admission and development of clinical DCI (odds ratio, 9.5, 95% confidence interval, 2.07-43.50; P= 0.004). None of the studied predictors was associated with the development of clinical DCI on multivariate analysis. Asymptomatic angiographic vasospasm in patients with good-grade aSAH on admission is uncommon. Further studies are needed to identify high-risk patients for the development of DCI in the context of asymptomatic early vasospasm.

Multidisciplinary Assessment in Optimising Results of Percutaneous Patent Foramen Ovale Closure.

Percutaneous patent foramen ovale (PFO) closure is a therapeutic option to prevent recurrent cerebral ischaemia in patients with cryptogenic stroke and transient cerebral ischaemia (TIA). The apparent lack of benefit seen in previous randomised trials has, in part, reflected inclusion of patients with alternate mechanisms of stroke. The role of formal neurology involvement in accurately delineating the likely aetiology of stroke or TIA is crucial in appropriate identification of patients for device closure. Furthermore, as the benefits of device closure may accrue over time, long-term follow-up is essential to define the role of device closure in management of presumed cryptogenic stroke. We retrospectively reviewed our experience with percutaneous PFO device closure since 2005. All subjects who underwent PFO closure at John Hunter and Lake Macquarie Private Hospitals were included in the study. All patients referred for device closure following cryptogenic stroke or TIA had first undergone formal neurology review with appropriate imaging and exclusion of paroxysmal atrial arrhythmia. Patients with a history of transient ischaemic attack (TIA) are frequently referred to a specialised clinic, aimed to identify patients with conditions not referable to cerebral ischaemia, with investigations initiated by the specialist clinic to elucidate an underlying aetiology. Outcome data was derived from the Hunter New England Area Local Health District Cardiac and Stroke Outcomes Unit, in addition to review of the medical record. The Cardiac and Stroke Outcomes Unit prospectively identified all patients presenting with stroke, TIA and atrial fibrillation. One hundred and twelve consecutive patients undergoing percutaneous patent foramen ovale closure between 2005 and 2015 were identified. The average age was 42.7 years and 57 (50.9%) patients were male. Cryptogenic stroke (68.8%) and transient cerebral ischaemia (23.2%) were the most common indications for PFO closure, with the Amplatzer device used in 83 cases (74.1%). Early residual shunting was visible in seven patients (6.3%), however on follow-up agitated saline study only two patients had residual shunt (1.8%). The annual risk of recurrent stroke or TIA was 0.21%. Percutaneous patent foramen ovale closure can be performed safely and effectively in patients with paradoxical embolism. In selected patients, following appropriate multidisciplinary specialist pre-procedural assessment, excellent long-term results with low incidence of recurrent events may be achieved.

Elevated Expression of Carboxy-Terminal Modulator Protein (CTMP) Aggravates Brain Ischemic Injury in Diabetic db/db Mice.

Deregulation of Akt signaling is important in the brain injuries caused by cerebral ischemia in diabetic animals, and the underlying mechanism is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following focal cerebral ischemia in type 2 diabetic db/db mice and their control littermates non-diabetic db/+ mice. db/db mice showed a significant elevation in the expression of CTMP compared to db/+ mice under normal physiological conditions. After ischemia, db/db mice exhibit higher levels of CTMP expression, decreased Akt kinase activity, adverse neurological deficits and cerebral infarction than db/+ mice. To further certain the effectiveness of Akt signaling to the final outcome of cerebral ischemia, the animals were treated with LY294002, an inhibitor of the Akt pathway, which aggravated the ischemic injury in db/+ mice but not in db/db mice. RNA interference-mediated depletion of CTMP were finally applied in db/db mice, which restored Akt activity, improved neurological scores and reduced infarct volume. These results suggest that elevation of CTMP in diabetic mice suppresses Akt activity and ultimately negatively affects the outcome of ischemia. Inhibitors specifically targeting CTMP may be beneficial in the treatment of cerebral ischemia in patients with diabetes.

Abstract TMP15: Circulating Antiangiogenic Profile Predicts Lower Degrees of Neovascularization After Indirect Revascularization With Encephaloduroarteriosynangiosis (EDAS) in Patients With Intracranial Atherosclerosis (ICAS)

Objective: To evaluate the hypothesis that circulating pro and antiangiogenic profiles predict the degree of angiographic neovascularization in patients undergoing EDAS for the treatment of symptomatic ICAS. Methods: This is a prospective observational study of circulating angiogenic factors in patients with arterial stenosis greater than 70% due to ICAS. All patients received intensive medical management. Patients with persistent symptoms underwent in addition EDAS revascularization. Twenty-one angiogenic factors were analyzed in serum samples collected at baseline, before surgery, using multiplex ELISA. All samples were run in duplicate and accepted as valid if the intersample variability was less than 20%. Patients have angiographic follow up 6 months after EDAS and a Neovascularization Index (NI) based on Perren grades and ASITN collaterals were calculated. Angiogenic profiles (APs) were defined using Principal Component Analysis (PCA). Seven profiles were selected for each time-point (Eigenvalue greater than 1.0). A regression model was built for the outcome variable NI using as predictor variables age, smoking history diabetes, and the 7 APs. Forward stepwise modeling with minimum BIC stopping rule was used to select the best fitted model. Results: Fifteen patients were enrolled. Mean age was 62.1 ± 12.3, 75% were females. The regression model demonstrated significant associations of age, diabetes and the AP 1-6 with the NI. Whole model P=0.023, Rsquare=0.93. The solution of the regression formula for the significant AP components revealed a strong negative association of the antiangiogenic factors endostatin and angiostatin (regression parameters -1.8 and -4.5, respectively, p=0.02). At 6 months follow up no patients had suffer strokes. Conclusion: In this prospective study of angiogenic factors in patients with ICAS undergoing EDAS revascularization, we have found that baseline levels of the antiangiogenic factors endostatin and angiostatin are significantly negatively associated to the degree of postoperative revascularization at 6 months. This finding supports the concept that neutralization of antiangiogenic factors may serve as a new pharmacological target to treat cerebral ischemia in patients with ICAS.

Abstract TMP23: Increased VEGFA-165a/VEGFA-165b Ratio in Patients With Moyamoya Compared to Intracranial Atherosclerosis (ICAS) and Controls

Introduction: Recent work in cancer biology has identified splice variants of human VEGF-A that inhibit angiogenesis. These isoforms arise from differential splicing of exon 8: a proangiogenic VEGF-A165a and the antiangiogenic VEGF-A165b. The purpose of this study was to compare circulating VEGF-A165a / VEGF-A165b ratios in patients with ICAS to those of patients with moyamoya and controls with no vascular or tumoral disease. Identifying a potential target to facilitate the generation of spontaneous collaterals could open novel treatment avenues for ICAS patients. Methods: This is a prospective observational study of circulating VEGF-A165a and VEGF-A165b. Serum samples were collected at baseline, 1 week, 1 month, 3 months, and 6 months after enrollment. Levels of VEGFA-165a and VEGFA-165b were determined by a multiplex sandwich ELISA. All samples were run in duplicate with an acceptance threshold for intersample variability of less than 20%. A mixed model regression model was built to predict square root transformed VEGF-A165a / VEGF-A165b ratio using age and etiology as the predictor variables. A repeated autoregressive 1 structure was used to account for repeated measures and subject random effects were used to account for intersubject variability. Results: The study population consisted of 72 individuals with ICAS (age = 61.7±12.0), 8 with moyamoya (age = 42.7±12.6), and 7 controls (age = 44.3±13.9). A total of 230 samples were collected (ICAS: 188, moyamoya: 21, control: 21). One outlier was excluded due to an exorbitantly high VEGFA-165a concentration. VEGFA-165a/VEGFA-165b ratios were as follows for each etiology: ICAS (0.15±0.17), moyamoya (0.38±0.52), and control (0.10±0.12). Mixed model regression analysis found a significant independent positive association of moyamoya to elevated VEGF-A165a/ VEGF-A165b ratio (p=0.03). Conclusion: In this prospective analysis of VEGF-A165a/ VEGF-A165b ratio, moyamoya patients had elevated ratios compared to ICAS and controls. This finding supports the concept that VEGF-A165b could serve as a new pharmacological target to treat cerebral ischemia in patients with ICAS as its neutralization may augment the activities of proangiogenic growth factors in developing collaterals.

The use of extra-intracranial microanastomosis in the treatment of cerebral ischemia in patients with nontraumatic subarachnoid hemorrhage

to evaluate the use of extra-intracranial microanastomosis (EICMA) in the treatment of brain ischemia in patients with nontraumatic subarachnoid hemorrhage (SAH). In the period from 01.01.14 to 01.07.15, there were 229 surgeries for ruptured intracranial aneurysms performed in the urgent surgery unit. Nine patients with marked and widespread angiospasm, subcompensated and decompensated cerebral ischemia underwent the simultaneous clipping of ruptured intracranial aneurysms and EICMA. The age of patients varied from 32 to 52 years (mean 36 years). The severity of patient's state was assessed as III-IV grades on the Hunt and Hess scale before operation. The surgery was performed 1-2 days after admission to the hospital, 1-8 days after the development of SAH. Excellent and good outcome was recorded in 4 patients, severe disability in 3 patients, fatal outcome in 2 patients. The fatal outcome was due to decompensated cerebral ischemia and progressive angiospasm with the high linear blood flow rate and the following reduction in perfusion in the affected hemisphere. The simultaneous clipping of ruptured intracranial aneurysms and EICMA in the acute stage of SAH of patients with subcompensated cerebral ischemia allow to improve treatment This technique is most applicable for patients with proximal angiospasm of M1- and M2-segments of the middle cerebral artery in the first 24 h of the development of a focal neurological deficit supported by the reduction in perfusion in the corresponding vascular area.

Preventive Antibiotics and Delayed Cerebral Ischaemia in Patients with Aneurysmal Subarachnoid Haemorrhage Admitted to the Intensive Care Unit.

Delayed cerebral ischemia (DCI) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Development of DCI is multifactorial, and inflammation, with or without infection, is one of the factors independently associated with development of DCI and poor outcome. We thus postulated that preventive antibiotics might be associated with a reduced risk of DCI and subsequent poor outcome in aSAH patients. We performed a retrospective cohort-study in intensive care units (ICU) of three university hospitals in The Netherlands. We included consecutive aSAH patients with minimal ICU stay of 72 h who received either preventive antibiotics (SDD: selective digestive tract decontamination including systemic cefotaxime or SOD: selective oropharyngeal decontamination) or no preventive antibiotics. DCI was defined as a new hypodensity on CT with no other explanation than DCI. Hazard ratio's (HR) for DCI and risk ratio's (RR) for 28-day case-fatality and poor outcome at 3 months were calculated, with adjustment (aHR/aRR) for clinical condition on admission, recurrent bleeding, aneurysm treatment modality and treatment site. Of 459 included patients, 274 received preventive antibiotics (SOD or SDD) and 185 did not. With preventive antibiotics, the aHR for DCI was 1.0 (95% CI 0.6-1.8), the aRR for 28-day case-fatality was 1.1 (95% CI 0.7-1.9) and the aRR for poor functional outcome 1.2 (95% CI 1.0-1.4). Preventive antibiotics were not associated with reduced risk of DCI or poor outcome in aSAH patients in the ICU.

Characterization of intracranial atherosclerotic stenosis using high-resolution MRI study--rationale and design.

Intracranial atherosclerosis is a leading cause of stroke, but little is known about the composition of the intracranial atherosclerotic lesion and how intracranial plaque morphology is related to the risk of stroke. High-resolution magnetic resonance imaging (HR MRI) has been used in patients with extracranial carotid atherosclerosis as an invivo tool to identify, with high-interrater agreement, histologically defined plaque components (i.e., intraplaque hemorrhage, fibrous cap, and lipid core), which have been shown to be predictors of recurrent stroke. With careful imaging the components ofatherosclerotic plaque can be visualized in the intracranial arteries using HRMRI, but there are no reports of reproducibility or interrater reliability. The Characterization of intracranial atherosclerotic stenosis using high-resolution MRI (CHIASM) study is a single-center NIH-funded prospective observational study, to (1) demonstrate high -interrater agreement for identifying intracranial plaque components on HR MRI, (2) determine the frequency of these components in symptomatic versus asymptomatic plaques, and (3) estimate the 1-year rate of stroke in the territory of high-risk plaque components. CHIASM will recruit 90 patients with 50-99% intracranial atherosclerosis to undergo HRMRI of the intracranial artery plaque at enrollment and 1-year follow-up. Both symptomatic and asymptomatic subjects will be recruited. Determination of good interrater reliability is an important first step in the development of HR MRI as a tool to predict risk in patients with intracranial atherosclerosis. This study will inform the design of future multicenter studies to determine the prevalence and prognosis of intracranial atherosclerotic plaque components. Such studies could lead to new understanding of the pathophysiological mechanisms of cerebral ischemia in patients with atherosclerotic intracranial stenosis, improvements in risk stratification, and potentially to new treatments of this common and serious disease.

The frequency of silent cerebral ischemia in patients with transfusion-dependent β-thalassemia major.

The aim of this study is to determine the frequency of silent cerebral ischemia (SCI) in a group of patients with β-thalassemia major and correlate them with demographic parameters, blood and spleen status, volume and frequency of transfusions. In this cross-sectional study, 40 β-thalassemic patients over 10years old who had no neurologic deficit were studied. Brain MRI was performed to detect SCI. Silent cerebral ischemia was classified according to number and size. Silent cerebral ischemia was found in 15 patients (37.5%). Mean number of SCI was 6.73 ± 10.33 (1-40), and mean size of the brain lesions was 3.07 ± 2.81mm (1-11mm). The patients with SCI were significantly older (31.1 ± 6.5 vs. 25 ± 6.8years, P = 0.009), and most of them were splenectomized (80% vs. 36%, P = 0.01). Interestingly, 10 out of 15 patients with SCI had platelet count less than 500,000/mm(3). Eight of these patients (80%) were splenectomized. Other variables had no statistically significant association with the presence of SCI. Older age and splenectomized multitransfused β-thalassemic patients even with normal platelet count have a higher incidence of SCI. The effect of splenectomy is more significant in statistical analysis. In splenectomized patients with a high platelet count and even with normal platelet count, aspirin therapy is indicated. Based on the results, it seems that regular blood transfusions are not going to have a significant effect on the number and size of SCI.

Investigation on in-stent recurrent stenosis after stenting of the extra-and intracranial artery in the elderly

Objective To investigate the distribution of in-stent recurrent stenosis (IRS) after balloon-angioplasty and stenting in elderly cerebral ischemic patient and its correlative factors. Methods Totally 158 elderly cerebral ischemic patients with extra-and/or intracranial artery stenosis were treated with 172 stents in our hospital. The inhibition of platelet function was assessed by using the thrombus elasticity chart system in perioperative period, and the anti-platelet agents were adjusted correspondingly. 150 patients were followed up by digital subtraction angiography (DSA) and the other 8 patients were followed up by CT angiography, during an average follow-up duration of 8.3 months. Results There were 11 (6.4%) IRS lesions, among which 10 lesions were at the vertebral artery origin and 1 lesion was at common carotid artery bifurcation. 23.8% of IRS happened after vertebral artery origin stenting, and all in-stent recurrent stenosis were in the origin of non-dominant vertebral artery, whose IRS rate was 66.7%. Conclusions IRS are more common found in vertebral artery origin than in other parts of vertebral artery and are more common found in non-dominant side than in dominant side. Key words: Stents; Angioplasty; Carotid stenosis; Vertebral artery

Testing of potential biomarkers of cerebral ischemia and vasospasm in patients with cerebral aneurysm surgery

Biomarkers for the prediction of vasospasm and delayed cerebral ischemia in patients with a ruptured cerebral aneurysm could be helpful.In this prospective clinical study, endothelin-1, lactate, pCO2, and pO2 were measured in arterial and internal jugular vein blood before, during and after surgical treatment of a cerebral aneurysm, and were tested as potential predictors of neurologic outcome in patients.Forty-one patients were enrolled in the study, 23 of them were operated on after aneurismal rupture with development of subarachnoid hemorrhage (SAH) and 18 patients were operated on for a nonruptured aneurysm.All of the involved patients survived. There was no difference in neurologic outcome between those operated on with a ruptured or nonruptured aneurysm.Endothelin-1 and lactate concentrations as well as pO2 and pCO2 from arterial and venous blood samples and their venoarterial difference did not differ between groups with and without an aneurismal rupture. Venoarterial difference of endothelin-1 concentrations on the day after surgery significantly differed between the groups with favorable and nonfavorable neurologic outcome. Other variables did not show a statistically significant difference.Significant correlation was found between endothelin-1 and lactate concentrations, suggesting involvement of the same pathophysiological process.Another interesting finding was lower arterial and venous pCO2 in patients with lower initial Glasgow Coma Scale (GCS) score and higher Hunt Hess score in the phase after extubation.We can conclude that the measured biochemical parameters did not show sufficient predictive power to be useful for prediction of cerebral vasospasm and neurologic outcome in everyday clinical practice. However, some correlations that do exist between them suggest involvement of the same pathophysiological process.

Preoperative beta blocker use associated with cerebral ischemia during carotid endarterectomy

Cerebral ischemia is a known complication of carotid cross-clamping during carotid endarterectomy. Selective intraluminal shunting for cerebral protection is not always effective and carries risks. The purpose of this study was to identify potentially modifiable risk factors for intraoperative cerebral ischemia and shunting during carotid endarterectomy. We performed an historical case-control chart review of primary carotid endarterectomies with electroencephalographic (EEG) monitoring and selective shunting. Randomized controls and cases that showed ischemic EEG changes and required shunting were matched by year of surgery and the presence or absence of a contralateral carotid occlusion. Detailed perioperative data were collected for all cases. Results were analyzed using the Mantel-Haenszel test, analysis of variance, and a multivariate logistic regression model. Of 523 charts screened, 69 patients had experienced evidence of cerebral ischemia on clamping of the carotid and required shunting. These patients were more likely than their matched controls to have been receiving regular preoperative beta blockers (33/69 vs 18/69, respectively; P = 0.01; odds ratio [OR] 2.5; 95% confidence interval [CI] 1.2 to 5.1). Ipsilateral moderate carotid stenosis (60-80%) was also associated with increased risk. An adjusted multivariate regression model estimated an OR of 3.6 (95% CI 1.5 to 8.9; P = 0.005) for the association between use of a beta blocker and shunting. Intraoperative hemodynamic values were similar for the shunt and control groups as well as for patients receiving and not receiving preoperative beta blockers. The current study found an association between regular preoperative use of beta blockers and intraoperative cerebral ischemia in patients undergoing carotid endarterectomy. This effect did not relate to intraoperative hemodynamics.

Abstract T P355: Dobutamine versus Mirlinone for Intensive Hemodynamic Augmentation to Relieve Clinical Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

Intensive hemodynamic augmentation by increasing cardiac output (CO) is a valuable method of elevating cerebral blood flow and oxygenation in the dysautoregulated vascular territories after subarachnoid hemorrhage (SAH). We prospectively assessed the effect of hyperdynamic therapy with dobutamine (DOB) or milrinone (MIL) on regional cerebral oxygenation (rSO 2 ) for reversing clinical deterioration induced by delayed cerebral ischemia, using an integrative monitoring with uncalibrated pulse contour CO analysis and multi-channel near-infrared spectroscopy. One-hundred ten SAH patients diagnosed to have clinical deterioration due to delayed cerebral ischemia were assigned to receive hemodynamic augmentation with DOB or MIL (n=56 per each group). For hyperdynamic therapy, each inotrope was initiated at low dose (DOB: 3μg/kg/min; MIL 0.15μg/kg/min) and then increased in each dose increment until resolution of the symptoms unless any adverse effects occur during the therapy, based on our predefined hemodynamic regimen to induce similar dose-related increase in CO. Real-time CO and rSO 2 changes in conjunction with the assessment of neurological improvements were compared. A total of 425 dose increment challenges (DOB, n=197; MIL, n=228) were performed. In spasm-affected territories, decreased and/or fluctuating rSO 2 was detected compared with recordings in other brain region. Patients who exhibited rapid elevation of CO by each challenge had subsequent uptake and stabilization of rSO 2 . The responses (total number and degree of neurological improvements) were more significant in patients treated with DOB than those treated with MIL ( P < 0.05), although tachycardia that may affect stroke volume depression during the DOB therapy was more evident (DOB 28% vs. MIL 9%). Area under the ROC curve to predict rSO 2 elevation or neurological improvement for both drug groups were significant ( P < 0.0001) and the values were significantly greater in DOB than in MIL ( P < 0.05). In conclusion, DOB can provide more effective hemodynamic augmentation in relieving focal cerebral ischemia in patients after SAH. MIL is also effective in the hyperdynamic therapy but may be used as a second line in a patient subgroup when DOB was contraindicated.

Accuracy of transcranial color-coded duplex sonography in predicting clinical vasospasm and delayed cerebral ischemia in patients with subarachnoid hemorrhage

Cerebral vasospasm (VSP) and delayed cerebral ischemia (DCI) play a central role in worsening the neurological outcome in patients with aneurismal subarachnoid hemorrhage (aSAH) [1]. Transcranial color-coded duplex sonography (TCCS) is a non-invasive tool to detect VSP and predict DCI, but its clinical utility is limited by low accuracy. Our aim was to perform a sensitivity/specificity analysis of TCCS in predicting clinical VSP and DCI.

Temporal profile of plasma adiponectin level and delayed cerebral ischemia in patients with subarachnoid hemorrhage

Adiponectin affects nitric oxide production, and low plasma adiponectin levels are associated with impaired endothelium-dependent vasorelaxation. However, adiponectin pathophysiology in the acute phase after stroke, especially subarachnoid hemorrhage, is not well understood. The present study evaluated the changes in plasma adiponectin concentrations in patients with subarachnoid hemorrhage and investigated the relationship between plasma adiponectin and delayed cerebral ischemia. Serial plasma samples from 27 patients with subarachnoid hemorrhage were obtained on day 0 or 1 after hemorrhage, and days 3, 7, 10, 14, and 21. As a control, plasma samples were obtained from 26 healthy volunteers. Differences between patients with and without delayed cerebral ischemia were assessed to investigate the relationship between plasma adiponectin concentrations and the occurrence of delayed cerebral ischemia. There were no significant differences in the clinical characteristics of patients with and without delayed cerebral ischemia. The plasma adiponectin concentrations were significantly lower in patients on days 3 and 7 compared with controls. Plasma adiponectin concentrations in patients with delayed cerebral ischemia were significantly lower than in those without delayed cerebral ischemia on days 3, 7, 10, and 14. The present results indicate that low plasma adiponectin concentrations from day 3 to day 14 might be associated with the development of delayed cerebral ischemia.

CT Perfusion for Detection of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Delayed cerebral ischemia is a significant cause of morbidity and mortality after aneurysmal SAH, leading to poor outcomes. The purpose of this study was to evaluate the usefulness of CTP in determining delayed cerebral ischemia in patients with aneurysmal SAH. We conducted a systematic review evaluating studies that assessed CTP in patients with aneurysmal SAH for determining delayed cerebral ischemia. Studies using any of the following definitions of delayed cerebral ischemia were included in the systematic review: 1) new onset of clinical deterioration, 2) cerebral infarction identified on follow-up CT or MR imaging, and 3) functional disability. A random-effects meta-analysis was performed assessing the strength of association between a positive CTP result and delayed cerebral ischemia. The systematic review identified 218 studies that met our screening criteria, of which 6 cohort studies met the inclusion criteria. These studies encompassed a total of 345 patients, with 155 (45%) of 345 patients classified as having delayed cerebral ischemia and 190 (55%) of 345 patients as not having delayed cerebral ischemia. Admission disease severity was comparable across all groups. Four cohort studies reported CTP test characteristics amenable to the meta-analysis. The weighted averages and ranges of the pooled sensitivity and specificity of CTP in the determination of delayed cerebral ischemia were 0.84 (0.7-0.95) and 0.77 (0.66-0.82), respectively. The pooled odds ratio of 23.14 (95% CI, 5.87-91.19) indicates that patients with aneurysmal SAH with positive CTP test results were approximately 23 times more likely to experience delayed cerebral ischemia compared with patients with negative CTP test results. Perfusion deficits on CTP are a significant finding in determining delayed cerebral ischemia in aneurysmal SAH. This may be helpful in identifying patients with delayed cerebral ischemia before development of infarction and neurologic deficits.

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

Danshen or Chinese red sage (Salvia miltiorrhiza, Bunge) is used by traditional Chinese medicine (TCM) practitioners to treat neurological, cardiovascular, and cerebrovascular disorders and is included in some TCM formulations to control epileptic seizures. In this study, acetonic crude extracts of danshen inhibited pentylenetetrazol (PTZ)-induced seizure activity in zebrafish larvae. Subsequent zebrafish bioassay-guided fractionation of the extract resulted in the isolation of four major tanshinones, which suppressed PTZ-induced activity to varying degrees. One of the active tanshinones, tanshinone IIA, also reduced c-fos expression in the brains of PTZ-exposed zebrafish larvae. In rodent seizure models, tanshinone IIA showed anticonvulsive activity in the mouse 6-Hz psychomotor seizure test in a biphasic manner and modified seizure thresholds in a complex manner for the mouse i.v. PTZ seizure assay. Interestingly, tanshinone IIA is used as a prescription drug in China to address cerebral ischemia in patients. Here, we provide the first in vivo evidence demonstrating that tanshinone IIA has anticonvulsant properties as well.

Acute paradoxical embolic cerebral ischemia secondary to possible May-Thurner syndrome and an atrial septal defect: a case report

IntroductionMay-Thurner syndrome is an anatomic abnormality that predisposes patients to increased risk of paradoxical embolism and stroke. It consists of chronic compression of the left common iliac vein by the overlying right common iliac artery which may predispose to local thrombus formation, which in turn may be the nidus of a paradoxical embolus leading to cerebral ischemia in patients with a right-to-left shunt secondary to an atrial septal defect or patent foramen ovale.Case presentationWe report the case of an embolic cerebral ischemic event in a 53-year-old Caucasian woman whose investigations revealed findings suggestive of possible May-Thurner syndrome coupled with an atrial septal defect. Her atrial septal defect was closed, she was placed on aspirin therapy, and has not had any recurrent events.ConclusionMay-Thurner syndrome is an important consideration in patients with paradoxical embolic cerebral ischemia and atrial septal defects.

Migraine is a marker for systemic disease

Dear Editor, We read with interest the article titled “Retinal arterial occlusions in the young: Systemic[1] associations in Indian population by Ratra et al. Authors have mentioned severe headache, floaters and transient blurring of vision as the presenting symptoms in a subset of patients. Visual aura (migraine) are fully reversible symptoms including positive features (e.g., flickering of lights, spots or lines) and negative features (i.e., loss of vision). A migraine diathesis may be a marker for an underlying defect such as hypertension, hypercoagulability, lupus erythematosis or mitral valve prolapse and therefore might occasionally co-occur with[2] vascular occlusion or retinal vasospasm. Experts disagree whether retinal migraine is a rare or common cause of monocular visual loss and whether the mechanism is spreading depression or vasospasm. Complicated migraine refers to a permanent neurologic deficit whether it is visual, motor or sensory in origin. In some instances the stroke does not respect the usual middle or posterior cerebral artery territories suggesting that a strict vascular mechanism is insufficient to[3] explain all migraine-related stroke phenomena. Cocaine abuse cause hypertensive surges, stroke, arterial and venous thrombosis. Neuroimaging studies in cocaine abusers demonstrated abnormal perfusion involving the infraparietal,[4] temporal and anterofrontal cortex and basal ganglia. Dopamine-rich brain regions appear to be relatively specific targets for cocaine-induced cerebral ischemia. Dopamine is one of the[5] numerous neurotransmitters present in outer and inner layers of the retina. Cocaine abuse,[3] exercise and lupus cause non-migrainous retinal vasospasm and transient monocular visual loss. Authors have documented hypertension, cerebrovascular accident and basal ganglia infarction in a 37-year-old patient. In our practice we routinely inform the possibility of underlying systemic disease and importance of physician consultation in all patients with migraine. Perimetry may be useful to identify coexisting cerebral ischemia in patients with retinal vascular occlusion and normal neuroimaging study. We appreciate the authors’ effort and research work.