Background and Purpose-The sulfonylurea receptor 1-regulated NC Ca-ATP channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume. We hypothesized that patients with type 2 diabetes mellitus taking sulfonylurea agents both at the time of stroke and during hospitalization would have superior outcomes. Methods-We reviewed medical records of patients with diabetes mellitus hospitalized within 24 hours of onset of acute ischemic stroke in the Neurology Clinic, Charité Hospital, Berlin, Germany, during 1994 to 2000. After exclusions, the cohort comprised 33 patients taking a sulfonylurea at admission through discharge (treatment group) and 28 patients not on a sulfonylurea (control group). The primary outcome was a decrease in National Institutes of Health Stroke Scale of 4 points or more from admission to discharge or a discharge National Institutes of Health Stroke Scale score of 0. The secondary outcome was a discharge modified Rankin Scale score Յ2. Results-No significant differences, other than stroke subtype, were observed among baseline variables between control and treatment groups. The primary outcome was reached by 36.4% of patients in the treatment group and 7.1% in the control group (Pϭ0.007). The secondary outcome was reached by 81.8% versus 57.1% (Pϭ0.035). Subgroup analyses showed that improvements occurred only in patients with nonlacunar strokes and were independent of gender, previous transient ischemic attack, and blood glucose levels. Conclusion-Sulfonylureas may be beneficial for patients with diabetes mellitus with acute ischemic stroke. Further investigation of similar cohorts and a prospective randomized trial are recommended to confirm the present observations. (Stroke. 2007;38:2526-2530.)Key Words: cerebral ischemia Ⅲ diabetes mellitus Ⅲ glibenclamide Ⅲ stroke Ⅲ sulfonylurea A cute stroke is the second leading cause of death in industrialized countries and is the leading medical cause of acquired adult disability. At present, thrombolysis is the only approved therapy, and for a variety of reasons, it is administered to less than 5% of patients with stroke. 1 There is an ongoing search for better prevention and treatment for acute stroke.The NC Ca-ATP channel is a nonselective cation channel that is expressed in the central nervous system only under conditions of injury or ischemia. [2][3][4] Channel opening, which is triggered by adenosine triphosphate depletion, results in cytotoxic edema, oncotic cell death, and cerebral edema. 5 Like the K ATP channel in pancreatic ␤ cells, it is regulated by sulfonylurea receptor 1 (SUR1) and is blocked by sulfonylureas such as glibenclamide (glyburide). Recently, Simard et al 4 reported that this channel is upregulated in rodent models of ischemic stroke, and that postevent block of the channel with glibenclamide reduces mortality, cerebral edema, and infarct volume by half.In patients with type 2 diabetes mellitus (DM), ...

Our study results indicate that lateral ventricle size is not affected in IIH. In contrast, abnormalities of the pituitary gland and optic nerve sheath were reliable diagnostic signs for IIH.

Objective Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1-regulated NCCa-ATP channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT. Methods We retrospectively analyzed data on 220 patients with DM who presented with acute ischemic stroke, 43 of whom were managed with and continued to receive SU drugs, and 177 of whom were managed without (controls). Results During a median length of stay in hospital of 11 days, 20 control patients (11%) experienced symptomatic HT (sHT), while no patient in the SU group experienced sHT (P=0.016). No patient in the SU group died, compared to 18 (10%) in the control group (P=0.027). Similarly favorable outcomes were observed after matching for baseline imbalances and excluding outliers. In support of the proposed mechanism, we present a case of sHT in which an analysis of brain tissues obtained intraoperatively showed prominent upregulation of SUR1, the target of SU drugs, in microvessels and neurons. Interpretation We conclude that, in diabetic patients with acute ischemic stroke, prior and continued use of SU drugs is associated with reduced sHT compared to those whose treatment regimen does not include SU drugs.

ObjectiveTo evaluate 3D spectral domain optical coherence tomography (SDOCT) volume scans as a tool for quantification of optic nerve head (ONH) volume as a potential marker for treatment effectiveness and disease progression in idiopathic intracranial hypertension (IIH).Design and PatientsCross-sectional pilot trial comparing 19 IIH patients and controls matched for gender, age and body mass index. Each participant underwent SDOCT. A custom segmentation algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D volume scans.ResultsWhereas peripapillary retinal nerve fiber layer thickness did not show differences between controls and IIH patients, the newly developed 3D parameters ONHV and ONHH were able to discriminate between controls, treated and untreated patients. Both ONHV and ONHH measures were related to levels of intracranial pressure (ICP).ConclusionOur findings suggest 3D ONH measures as assessed by SDOCT as potential diagnostic and progression markers in IIH and other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic alternative to repeated lumbar punctures and could therefore ease monitoring of treatment or disease progression.

BackgroundPlaque neovascularization accompanies local inflammation and critically contributes to plaque instability. Correct identification of intraplaque neovascularization by contrast–enhanced ultrasound (CEUS) may provide an additional risk marker in carotid stenosis. This pilot study investigates the correlation between histological evaluation of carotid plaque specimens and pre-surgery CEUS to identify neovascularization.Methods17 patients with high-grade internal carotid artery (ICA) stenosis were studied. CEUS was performed in all patients shortly before carotid endarterectomy. Neovascularization, infiltration of T cells and macrophages along with intraplaque hemorrhage were studied in excised plaques by immunohistochemistry. Ultrasound-based four-level and two-level classification systems for neovascularization were used. CEUS findings were compared with histological findings.ResultsScores on the CEUS-based four-level and two-level classifications were robustly correlated with the density of intraplaque vessels (r = 0.635, p = 0.006 and r = 0.578, p = 0.015, respectively). Histological evaluation of regions with strong and prolonged intraplaque enhancement typically showed strong intraplaque neovascularization in conjunction with acute intraplaque hemorrhage. Moreover, higher grades of intraplaque neovascularization as determined by ultrasound were associated with a higher percentage of macrophage-rich areas.ConclusionCEUS is a technique well suited to gauge the degree of neovascularization of carotid plaques. Future research will have to define the reliability and validity of CEUS in everyday clinical practice. Further, our study suggests that CEUS may also be useful to pick up features of vulnerable plaques such as acute intraplaque hemorrhages.

Our results confirm the value of percentage of macrophage area and percentage of MMP-9 area as markers of plaque instability and provide further evidence to support the hypothesis that statins reduce inflammatory responses and thereby stabilize carotid atherosclerotic plaques.

BACKGROUND AND PURPOSE:Idiopathic intracranial hypertension is a headache syndrome characterized by increased CSF pressure. Compression of the hypophysis and distension of the optic nerve sheath are reliable imaging signs. The purpose of the study was to validate, in patients with idiopathic intracranial hypertension, MR imaging-based volumetric measurements of the optic nerve sheath and hypophysis as an objective observation method for more accurate diagnosis and posttreatment follow-up.

Our pilot study provides new evidence that olfaction is impaired in patients with IIH, especially in those who have been newly diagnosed or who have experienced a recent clinical deterioration.