Subject to the usual caveats inherent in studies with small sample size, this pilot phase 2 study supports further investigation of this novel treatment strategy using a metal-protein-attenuating compound.

Most patients with non-lesional temporal lobe epilepsy (NLTLE) will have the findings of hippocampal sclerosis (HS) on a high resolution MRI. However, a significant minority of patients with NLTLE and electroclinically well-lateralized temporal lobe seizures have no evidence of HS on MRI. Many of these patients have concordant hypometabolism on fluorodeoxyglucose-PET ([18F]FDG-PET). The pathophysiological basis of this latter group remains uncertain. We aimed to determine whether NLTLE without HS on MRI represents a variant of or a different clinicopathological syndrome from that of NLTLE with HS on MRI. The clinical, EEG, [18F]FDG-PET, histopathological and surgical outcomes of 30 consecutive NLTLE patients with well-lateralized EEG but without HS on MRI (HS-ve TLE) were compared with 30 consecutive age- and sex-matched NLTLE patients with well-lateralized EEG with HS on MRI (HS+ve TLE). Both the HS+ve TLE group and the HS-ve TLE patients had a high degree of [18F]FDG-PET concordant lateralization (26 out of 30 HS-ve TLE versus 27 out of 27 HS+ve TLE). HS-ve TLE patients had more widespread hypometabolism on [18F]FDG-PET by blinded visual analysis [odds ratio (OR = + infinity (2.51, -), P = 0.001]. The HS-ve TLE group less frequently had a history of febrile convulsions [OR = 0.077 (0.002-0.512), P = 0.002], more commonly had a delta rhythm at ictal onset [OR = 3.67 (0.97-20.47), P = 0.057], and less frequently had histopathological evidence of HS [OR = 0 (0-0.85), P = 0.031]. There was no significant difference in surgical outcome despite half of those without HS having a hippocampal-sparing procedure. Based on the findings outlined, HS-ve PET-positive TLE may be a surgically remediable syndrome distinct from HS+ve TLE, with a pathophysiological basis that primarily involves lateral temporal neocortical rather than mesial temporal structures.

on behalf of the VISTA Investigators Background and Purpose-In the first 3 months after acute ischemic stroke, 2% to 6% of patients die from cardiac causes.This may reflect preexisting cardiac disease, cardiac dysfunction related to the acute neurohumoral and autonomic stress response to stroke, or both. Delineation of a high-risk group could facilitate prevention strategies. We aimed to describe the temporal profile of cardiac risk after stroke and develop a predictive model of serious cardiac adverse events (SCAEs) using baseline variables. Methods-We used data from the one trial in the Virtual International Stroke Trials Archive that matched prespecified criteria. Survival analysis was used to describe the temporal profile of cardiac events after stroke. Prognostic determinants were assessed with multivariable logistic regression, and a risk score was derived from the key predictor variables. Results-Of

Background and Purpose-The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis.There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. Methods-Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT

Studies have shown that dual therapy with angiotensin-converting enzyme inhibitors (ACEI) and either angiotensin II receptor blockers or aldosterone receptor antagonists is more effective in reducing proteinuria than either agent used alone. The questions that remain are as follows: (1) Which of these agents should be used as dual therapy with the ACEI? (2) Does a higher level of blockade of the renin-angiotensin-aldosterone system with triple therapy offer an advantage over dual blockade? A 3-mo randomized, double-blind, placebo-controlled study was performed in 41 patients with proteinuria >1.5 g/d. Four treatment groups were compared: (1) Ramipril ؉ spironolactone placebo ؉ irbesartan placebo, (2) ramipril ؉ irbesartan ؉ spironolactone placebo, (3) ramipril ؉ irbesartan placebo ؉ spironolactone, and (4) ramipril ؉ irbesartan ؉ spironolactone. The percentage change in protein excretion differed according to treatment arm (ANOVA: F 3,35 ‫؍‬ 8.6, P < 0.001). Pair-wise comparison showed that greater reduction in protein excretion occurred in treatment regimens that incorporated spironolactone. The reduction in proteinuria at 3 mo was as follows: Group 1, 1.4%; group 2, 15.7%; group 3, 42.0%; and group 4, 48.2%. The reduction in proteinuria among patients who were taking spironolactone-containing regimens was sustained at 6 and 12 mo. This study suggests that aldosterone receptor blockade offers a valuable adjuvant treatment when used with ACEI therapy for the reduction of proteinuria. Results suggest no advantage of triple blockade over dual blockade of the renin-angiotensin-aldosterone system to reduce proteinuria.

Background and Purpose-Intracerebral hemorrhage (ICH) growth predicts mortality and functional outcome. We hypothesized that irregular hematoma shape and density heterogeneity, reflecting active, multifocal bleeding or a variable bleeding time course, would predict ICH growth. Methods-Three raters examined baseline sub-3-hour CT brain scans of 90 patients in the placebo arm of a Phase IIb trial of recombinant activated Factor VII in ICH. Each rater, blinded to growth data, independently applied novel 5-point categorical scales of density and shape to randomly presented baseline CT images of ICH. Density and shape were defined as either homogeneous/regular (Category 1 to 2) or heterogeneous/irregular (Category 3 to 5). Within-and between-rater reliability was determined for these scales. Growth was assessed as a continuous variable and using 3 binary definitions: (1) any ICH growth; (2) Ն33% or Ն12.5 mL ICH growth; and (3) radial growth Ͼ1 mm between baseline and 24-hour CT scan. Patients were divided into tertiles of baseline ICH volume: "small" (0 to 10 mL), "medium" (10 to 25 mL), and "large" (25 to 106 mL). Results-Inter-and intrarater agreements for the novel scales exceeded 85% (Ϯ1 category). Median growth was significantly higher in the large-volume group compared with the small group (PϽ0.001) and in heterogeneous compared with homogeneous ICH (Pϭ0.008). Median growth trended higher in irregular ICHs compared with regular ICHs (Pϭ0.084). Small ICHs were more regularly shaped (43%) than medium (17%) and large (3%) ICHs (PϽ0.001). Small ICHs were more homogeneous (73%) compared with medium (37%) and large (17%) ICHs (PϽ0.001). Adjusting for baseline ICH volume and time to scan, density heterogeneity, but not shape irregularity, independently predicted ICH growth (Pϭ0.046) on a continuous growth scale. Conclusions-LargeICHs were significantly more irregular in shape, heterogeneous in density, and had greater growth.Density heterogeneity independently predicted ICH growth using some definitions. Key Words: density Ⅲ growth Ⅲ intracerebral hemorrhage Ⅲ recombinant activated factor VII Ⅲ predictors Ⅲ shape I ntracerebral hemorrhage (ICH) is the most sinister stroke subtype with a high early mortality. 1,2 Despite this, there is convincing evidence that aggressive care can bring about meaningful recovery, even in the worst initial prognostic groups. 3,4 CT scanning remains the standard diagnostic technique for ICH. Hematoma growth occurs in Ͼ70% of patients on CT performed within 3 hours of symptom onset and independently predicts mortality and functional outcome. 5 Hemostatic therapy has been demonstrated to attenuate ICH growth in 2 pivotal studies of recombinant activated Factor VII administered within 4 hours of symptom onset. 6,7 In contrast, the clinical outcomes in these trials were discordant and the positive results were not replicated in the second, larger trial. 6,7 Attenuated hematoma growth has also been suggested in an acute blood pressure reduction trial. 8 Hence, hematoma growth is a key therapeu...

Female genital tract graft-versus-host disease (GVHD) is an under-recognized complication of allogeneic stem cell transplantation impacting on quality of life. We describe a prospective surveillance programme for female genital GVHD to better characterize incidence, risk factors and clinical features and the impact of a structured intervention policy. A retrospective audit was conducted on the medical records of all female transplant recipients surviving at least 6 months at a single centre over a 5-year period. Patients commenced topical vaginal oestrogen early post transplant with hormone replacement as appropriate for age, prior menopausal status and comorbidities. A genital tract management programme included regular gynaecological review and self-maintenance of vaginal capacity by dilator or intercourse. The incidence of genital GVHD was 35% (95% confidence interval (CI) (25, 50%)) at 1 year and 49% (95% CI (36, 63%)) at 2 years. Topical therapy was effective in most cases; no patient required surgical intervention to divide vaginal adhesions. The main risk factor was stem cell source with peripheral blood progenitor cells posing a higher risk than marrow (hazard ratio ¼ 3.07 (1.22, 7.73), P ¼ 0.017). Extensive GVHD in other organs was a common association. We conclude that female genital GVHD is common, and early detection and commencement of topical immunosuppression with dilator use appears to be highly effective at preventing progression.

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