Simona Lattanzi

Neutrophil-to-Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage

Background and Purpose— Increasing evidence suggests that inflammatory mechanisms are involved in the intracerebral hemorrhage–induced brain injury. We evaluated the prognostic role of the peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) in patients with intracerebral hemorrhage. Methods— Patients with acute spontaneous intracerebral hemorrhage were retrospectively identified. Total white blood cells, absolute neutrophil count, and absolute lymphocyte count were obtained and the NLR computed from the admission blood work. The study end point was the occurrence of death or major disability at 3 months. Results— One hundred seventy-seven subjects were enrolled. Ninety-four (53.1%) had unfavorable outcome. The absolute neutrophil count, absolute lymphocyte count, and NLR were independently associated with the 3-month status. The NLR resulted the best discriminating variable and the best predictive cut-off value was 4.58. Conclusions— In patients with acute intracerebral hemorrhage, higher neutrophils, lower lymphocytes, and higher NLRs predicted worse 3-month outcome.

How Should We Lower Blood Pressure after Cerebral Hemorrhage? A Systematic Review and Meta-Analysis.

Background: The optimal treatment of high blood pressure (BP) after acute intra-cerebral hemorrhage (ICH) is controversial. Summary: The aim of the study was to evaluate the safety and efficacy of early intensive vs. conservative BP lowering treatment in patients with ICH. Randomized controlled trials with active and control groups receiving intensive and conservative BP lowering treatments were identified. The following outcomes were assessed: 3-month mortality and combined death or major disability, 24-h hematoma growth, early neurological deterioration, occurrence of hypotension, severe hypotension, and serious treatment-emergent adverse events. Five trials were included involving 4,350 participants, 2,162 and 2,188 for intensive and conservative treatment groups, respectively. The pooled risk ratio of 3-month death or major disability was 0.96 (0.91-1.01) and the weighted mean difference in absolute hematoma growth was -1.53 (95% CI -2.94 to -0.12) mL in the intensive compared to conservative BP-lowering. There were no differences across the treatments in the incidence rates of 3-month mortality, early neurological deterioration, hypotension, and treatment-related adverse effects other than renal events. Key Messages: The early intensive anti-hypertensive treatment was overall safe and reduced the hematoma expansion in patients presenting with acute-onset spontaneous ICH and high BP levels.

Brivaracetam add-on for refractory focal epilepsy A systematic review and meta-analysis

Objective: To evaluate the efficacy and safety of the new antiepileptic drug brivaracetam (BRV) as add-on treatment for drug-resistant partial epilepsy using meta-analytical techniques. Methods: Randomized, placebo-controlled, single- or double-blind, add-on trials of BRV in adult patients with drug-resistant partial epilepsy were identified through a systematic literature search. The following outcomes were assessed: 50% or greater reduction in seizure frequency, seizure freedom, incidence of treatment-emergent adverse events (TEAEs), and treatment withdrawal. Risk ratio (RR) with 95% confidence interval was estimated for each outcome. Results: Six trials were included involving 2,399 participants according to the intent-to-treat, 1,715 for BRV, and 684 for placebo groups, respectively. The pooled RRs for the 50% responders and seizure freedom were 1.79 (1.51–2.12) and 4.74 (2.00–11.25), respectively. The subanalysis by levetiracetam (LEV) status did not show a statistically significant difference in the 50% responder rate when comparing BRV with placebo in patients with concomitant assumption of LEV. The TEAEs significantly associated with BRV were irritability (2.99 [1.28–6.97]), fatigue (2.19 [1.44–3.33]), somnolence (1.97 [1.45–2.68]), and dizziness (1.66 [1.19–2.31]). The overall RRs for treatment withdrawal due to TEAEs or any reason were 1.58 (1.04–2.40) and 1.27 (0.93–1.73), respectively. Conclusions: In adults with drug-refractory focal epilepsy, add-on BRV was effective to reduce seizure frequency and fairly well-tolerated. Further studies are needed to draw definitive conclusions about its efficacy in non-LEV-naive participants and evaluate its long-term safety profile.

Blood Pressure Variability and Clinical Outcome in Patients with Acute Intracerebral Hemorrhage

BACKGROUND The aim of this study was to evaluate whether fluctuations of blood pressure (BP) levels occurring in the acute stage of spontaneous intracerebral hemorrhage (ICH) affect the 3-month clinical outcome. METHODS We retrospectively identified consecutive patients hospitalized for acute spontaneous ICH. BP measurements over the first 72 hours from the onset of symptoms were recorded, and standard deviation (SD), coefficient of variation (CV), and maximum-minimum difference (max-min) were determined to characterize both systolic and diastolic BP variability (BPV). The measure of outcome was the 3-month functional status assessed by the modified Rankin Scale following a baseline severity-adjusted analysis. RESULTS Among the 138 enrolled patients with ICH, 67 (48.6%) were classified as having a poor 3-month functional recovery. A dose-response relationship with poor outcome was found for each measure of systolic BPV--adjusted odds ratios (ORs) for the highest thirds of SD 7.95 (95% confidence interval [CI], 2.88-21.90), CV 7.74 (95% CI, 2.88-20.80), and max-min 8.36 (95% CI, 2.72-25.62; P < .001). The strength of association with diastolic BPV turned out to be weaker and significant only for the higher values (adjusted ORs for the highest thirds of SD 6.74 [95% CI, 2.52-18.04], CV 4.57 [95% CI, 1.77-11.81], and max-min 4.34 [95% CI, 1.72-10.93]). CONCLUSIONS In patients with acute ICH, BPV was a strong predictor of the 3-month clinical outcome and may represent a still neglected potential therapeutic target.

Blood pressure variability and stroke outcome in patients with internal carotid artery occlusion

PURPOSE The aim of this study was to evaluate the relationship between arterial blood pressure (BP) variability during the acute phase and the 3-month outcome in ischemic stroke patients with internal carotid artery (ICA) occlusion. METHODS At least 10 BP measurements during the first 48 h after stroke onset were obtained in 89 patients with ICA occlusion. BP profile was described using various parameters: average of recordings, maximum (max), minimum (min), difference between max and min (max-min), standard deviation (SD) and coefficient of variation (CV) for both systolic and diastolic BP. Outcome at 3 months was defined using the modified Rankin Scale (mRS) score corrected for baseline stroke severity. RESULTS Fifty-five patients had a good and 34 a poor outcome. Max values, max-min, SD and CV of both systolic and diastolic BP resulted significantly higher in patients with poor outcome compared to those with good outcome (p<0.05, multivariate adjusted model). CONCLUSIONS In a cohort of acute ischemic stroke patients with ipsilateral ICA occlusion BP variability, assessed in the acute phase, was associated with poor clinical outcome. These preliminary exploratory findings are worthy of further study to be conducted to confirm or confute the role of BP variability in predicting stroke outcome. In order to obtain more comprehensive information, it would also be appropriate to consider the possibility of acquiring data related to the pathophysiology of stroke and to cerebral hemodynamic changes.

Blood pressure variability predicts cognitive decline in Alzheimer's disease patients

The aim of our study was to evaluate whether blood pressure variability influences the rate of cognitive decline in Alzheimers disease (AD). Two hundred and forty AD patients were periodically evaluated for a 12-month period. The blood pressure (BP) status of each patient was defined through mean and coefficient of variation for both systolic and diastolic BP. Progression of cognitive decline was investigated using the Mini Mental State Examination administered at entry and at the end of follow-up. Among the considered BP indices, only systolic BP variability explained the decrease in the Mini Mental State Examination score after adjustment for confounding variables (multiple linear regression: R(2) = 0.603, adjusted R(2) = 0.513; p < 0.001; logistic regression model: odds ratio = 2.882, 95% confidence interval = 1.772-4.495; p < 0.001). The receiver operating characteristic analysis for evaluating the ability of systolic BP variability to predict a faster cognitive decline presented an area under the curve of 0.913 (95% confidence interval = 0.874-0.953; p < 0.001). Our results suggest that BP variability may be added to the list of the potential vascular risk factors and included in the evaluation of AD patients to better define their risk profile.

Elevated Blood Pressure in the Acute Phase of Stroke and the Role of Angiotensin Receptor Blockers

Raised blood pressure (BP) is common after stroke but its causes, effects, and management still remain uncertain. We performed a systematic review of randomized controlled trials that investigated the effects of the angiotensin receptor blockers (ARBs) administered in the acute phase (≤72 hours) of stroke on death and dependency. Trials were identified from searching three electronic databases (Medline, Cochrane Library and Web of Science Database). Three trials involving 3728 patients were included. Significant difference in BP values between treatment and placebo was found in two studies. No effect of the treatment was seen on dependency, death and vascular events at one, three or six months; the cumulative mortality and the number of vascular events at 12 months differed significantly in favour of treatment in one small trial which stopped prematurely. Evidence raises doubts over the hypothesis of a specific effect of ARBs on short- and medium-term outcomes of stroke. It is not possible to rule out that different drugs might have different effects. Further trials are desirable to clarify whether current findings are generalizable or there are subgroups of patients or different approaches to BP management for which a treatment benefit can be obtained.

Visit-to-visit blood pressure variability in Alzheimer disease.

The aim of this study was to evaluate visit-to-visit blood pressure (BP) variability in a cohort of patients with Alzheimer disease (AD) and healthy controls. Patients with clinically diagnosed mild or moderate AD and cognitively normal controls matched for age and sex were recruited and followed up for 6 months. To characterize the BP status of each individual, mean, maximum and minimum values, SD, and coefficient of variation were obtained for both systolic BP (SBP) and diastolic BP (DBP). Seventy AD patients and 140 controls were enrolled. No meaningful differences were found in prevalence or treatments of various vascular risk factors. AD patients had higher maximum and lower minimum values and greater SD and coefficient of variation of both SBP and DBP. Group differences in mean values were significant only for SBP. In the multiple logistic regression analysis, adjusted for confounding variables, all the indices related to BP variability were significantly associated with AD. Our results show that AD patients have a greater variability of both SBP and DBP in comparison with age-matched cognitive normal controls, suggesting potential implication in the pathogenesis or progression of the disease.

Glycosylated Hemoglobin and Functional Outcome after Acute Ischemic Stroke

BACKGROUND Diabetes mellitus (DM) is associated to an increased incidence of cerebral and myocardial infarction which could be reduced by long-term maintenance of optimal glycemic values. The aim of the study was to evaluate in diabetic patients with ischemic stroke the chronic glycemic status and its relationship with functional outcome. METHODS We retrospectively identified consecutive diabetic patients hospitalized for acute ischemic stroke. Clinical and biochemical characteristics at admission were assessed. The outcome measures were the attainment of the recommended glycosylated hemoglobin A1 (HbA1c) level and the 3-month functional status according to the modified Rankin Scale score. RESULTS Among the 112 enrolled patients, 39 (34.8%) met the recommended goal of HbA1c less than 7%. Higher education level was predictive of good prestroke glycemic control (adjusted OR 1.32 per year [95% CI 1.15-1.51], P < .001). At the 3-month evaluation, 44 (39.3%) patients were classified as having a poor outcome. After categorization of HbA1c values into tertiles, a dose-response relationship with poor functional recovery was found (P = .001). The suboptimal prestroke glycemic status was an independent predictor of unfavorable outcome (adjusted OR 6.22 [95% CI 1.94-19.98] for HbA1c ≥7%, P = .002). CONCLUSIONS The management of DM was suboptimal in nearly two thirds of diabetic subjects presenting with acute ischemic stroke. The glycemic control before stroke occurrence was an independent prognostic factor and HbA1c values above the recommended goals increased the risk of unfavorable 3-month outcome. The improvement of DM management may be an effective strategy to either decrease the burden of cerebrovascular disease or influence its clinical course.

Blood Pressure Variability in Alzheimer's Disease and Frontotemporal Dementia: The Effect on the Rate of Cognitive Decline

BACKGROUND The link between vascular disease and cognitive impairment is a matter of an ongoing debate, and different cardiovascular conditions have been found to be predictors of the clinical development and progression of cognitive dysfunction. OBJECTIVE To compare the influence of visit-to visit blood pressure (BP) variability on the rate of cognitive decline in Alzheimers disease (AD) and frontotemporal dementia (FTD). METHODS The patients affected by AD and FTD consecutively admitted to our center from January 2007 to September 2012 were evaluated every three months for a one-year period. The BP mean and coefficient of variation as index of variability were obtained for both systolic and diastolic values. Progression of cognitive decline was investigated using the Mini-Mental State Examination administered at entry and at the end of the follow-up. RESULTS Two-hundred and forty-eight AD and eighty-one FTD patients were enrolled. Systolic and diastolic BP mean and variability were comparable between the two groups. Systolic BP variability (BPV) was associated with the rate of cognitive impairment in AD (B = 0.367, beta = 0.739, R2 = 0.594, adjusted R(2) = 0.567; p < 0.001), but not in FTD patients; no relationship emerged between any other BP index and cognitive decline. CONCLUSION The relationship between BPV and cognitive function is still not completely understood, and it may play different roles according to the types and stages of dementia. Fluctuations in systolic BP may contribute to the cognitive decline in AD patients and may represent a neglected therapeutic target.