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.
Spontaneous intracerebral hemorrhage (ICH) accounts for 10–30% of all strokes and affects more than one million people every year worldwide, and it is the stroke subtype associated with the highest ...rates of mortality and residual disability. So far, clinical trials have mainly targeted primary cerebral injury and have substantially failed to improve clinical outcomes. The understanding of the pathophysiology of early and delayed injury after ICH is, hence, of paramount importance to identify potential targets of intervention and develop effective therapeutic strategies. Matrix metalloproteinases (MMPs) represent a ubiquitous superfamily of structurally related zinc-dependent endopeptidases able to degrade any component of the extracellular matrix. They are upregulated after ICH, in which different cell types, including leukocytes, activated microglia, neurons, and endothelial cells, are involved in their synthesis and secretion. The aim of this review is to summarize the available experimental and clinical evidence about the role of MMPs in brain injury following spontaneous ICH and provide critical insights into the underlying mechanisms.
The optimal treatment of high blood pressure (BP) after acute intra-cerebral hemorrhage (ICH) is controversial.
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.
The inflammatory response plays a role in determining the course of intra-cerebral hemorrhage (ICH) and immune parameters may have prognostic value. The aim of the study was to determine whether the ...peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) were associated to 30-day functional status after ICH, and improved the accuracy of outcome prediction when added to the Modified ICH score.
We retrospectively identified consecutive patients with spontaneous ICH who underwent blood sampling and cranial CT neuroimaging within 24 h from onset. Total white blood cells (WBC), absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected, and the NLR computed as the ANC to ALC ratio. The study endpoint was 30-day functional status; poor outcome was defined as death or major disability (modified Rankin Scale score ≥ 3).
Two hundred and eight patients were enrolled, of which 111 (53.4%) had a modified Rankin Scale score ≥ 3 at 30 days from ICH. At multivariate analysis, the WBC (adjusted odd ratio adjOR for 1000 leukocytes increase 1.20, 95% confidence interval CI 1.05–1.38), ANC (adjOR for 1000 neutrophils increase 1.34, 95% CI 1.14–1.57), ALC (adjOR for 1000 lymphocytes increase 0.34, 95% CI 0.20–0.59) and NLR (adjOR for 1-point increase 1.49, 95% CI 1.24–1.79) were independently associated with 30-day poor outcome. Predictive accuracy of the Modified ICH score was enhanced by adding the NLR.
The NLR was associated with 30-day mortality and morbidity after ICH, and improved the accuracy of outcome prediction when added to the Modified ICH score.
•Inflammatory response can influence the course of intra-cerebral hemorrhage (ICH).•Immune parameters may have prognostic value in the setting of acute ICH.•The neutrophil-to-lymphocyte ratio (NLR) predicted 30-day outcome after ICH.•The NLR improved the accuracy of outcome prediction of the Modified ICH score.
Objective
To estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in the elderly with new‐onset epilepsy.
Methods
We searched electronic databases for randomized controlled ...trials (RCTs) of monotherapy AEDs to treat epilepsy in elderly. The following outcomes were analyzed: seizure freedom and withdrawal from the study for any cause at 6 and 12 months; withdrawal from the study for any adverse event (AE) at 12 months; and occurrence of any AE at 12 months. Effect sizes were estimated by network meta‐analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks.
Results
Five RCTs (1425 patients) were included. Included AEDs were carbamazepine immediate‐ and controlled‐release (CBZ‐IR, CBZ‐CR), gabapentin (GBP), lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), phenytoin (PHT), and valproic acid (VPA). At the pairwise and network meta‐analyses, there were no differences in any of the comparison according to 6‐ and 12‐month seizure freedom. The treatment with CBZ‐IR and CBZ‐CR was associated with a higher risk of withdrawal than LTG, LEV, or VPA, and CBZ‐IR had the overall highest probability of discontinuation across all AEDs. According to SUCRA, the following had the greatest likelihood ranking best for seizure freedom at 6 and 12 months: LCM, LTG, and LEV. CBZ‐CR and CBZ‐IR had the highest probabilities of being worst for the 12‐month retention. CBZ‐IR, CBZ‐CR, and GBP had the highest probabilities of withdrawal from the study for AEs, , and VPA had the highest probability of being the best‐tolerated option.
Significance
Although no significant difference in efficacy was found across treatments, LCM, LTG, and LEV had the highest probability of ranking best for achieving seizure freedom. CBZ‐IR and CBZ‐CR showed a poor tolerability profile, leading to higher withdrawal rates compared to LEV and VPA.
Abstract The aim of our study was to evaluate whether blood pressure variability influences the rate of cognitive decline in Alzheimer's 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: R2 = 0.603, adjusted R2 = 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.
Comorbidity between epilepsy and infectious diseases in children is frequent. Pharmacokinetic drug‐drug interactions (DDIs) between antiseizure medications (ASMs) and anti‐infectives can occur and ...influence their efficacy or cause toxicity. All potential DDIs between ASMs and antimicrobial agents used in children were identified through consultation of drug compendia. Clinical studies, case reports and summaries of product characteristics of all identified drugs were also searched. A typical example of a DDI that is often observed in children is that involving valproate (VPA) and carbapenem antibiotics. This DDI has a unique mechanism of action (inhibits the enzyme that catalyses the hydrolysis of VPA‐glucuronide) and leads to a fall of around 60% of VPA level, associated with seizure recurrence. An example of bidirectional DDI involves the antimycotic voriconzole and several ASMs. Voriconazole is metabolized and is a strong inhibitor of cytochrome (CYP)3A4, CYP2C9/10 and CYP2C19. There is clinical evidence of induction of voriconazole metabolism with possible loss of its efficacy by phenytoin (PHT), while voriconazole increases the levels of PHT. Other ASMs that are inducers of these enzymes, such as carbamazepine (CBZ), phenobarbital, stiripentol and to a lesser degree, oxcarbazepine, might be predicted to decrease the level of voriconazole. Voriconazole might also be predicted to increase levels of cannabidiol, CBZ, lacosamide, midazolam, and zonisamide. DDIs between ASMs and some antiviral agents are potentially even more frequent and clinically relevant.
OBJECTIVETo evaluate in patients with TIA and ipsilateral high-grade internal carotid artery (ICA) stenosis whether changes in cognitive performance and cerebral hemodynamics occurred after carotid ...endarterectomy (CEA) and to explore their relationship.
METHODSParticipants were patients who underwent CEA, had TIA within the last 6 months, and had an ipsilateral severe ICA stenosis. Coloured Progressive Matrices (CPM) plus Complex Figure Copy Test (CFCT) and phonemic (ph) plus categorical (ca) Verbal Fluency (VF) tests were performed to assess right and left hemisphere cognitive functions, respectively. Hemodynamics was assessed with transcranial Doppler ultrasonography by means of the cerebral vasomotor reactivity (CVR) to hypercapnia.
RESULTSA total of 137 patients were included. Before CEA, patients with right ICA obtained lower scores on the CPM and CFCT; patients with left ICA stenosis performed worse on the phonemic and categorical VF tests. The CVR was decreased on the side of the stenosis. At 6 months from CEA, CVR and cognitive performance were significantly improved. The performance change in cognitive tests exploring the revascularized hemisphere was positively associated with the ipsilateral CVR variation (CPMR for linear regression = 0.759, adjR = 0.737; CFCTR = 0.734, adjR = 0.710; (ph)VFR = 0.774, adjR = 0.749; (ca)VFR = 0.732, adjR = 0.703).
CONCLUSIONCognitive performance was enhanced at 6 months since CEA, and the improvement was related to the CVR increase. Cerebral hemodynamics may be an independent and potentially reversible determinant of cognitive dysfunction in severe carotid artery disease.
Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses, but the most desirable route of administration is still matter of debate. The aim of the study was to compare the ...efficacy and safety of oral versus intravenous steroids for treatment of acute relapses in patients with MS. Randomized or quasi-randomized, parallel group trials with direct comparison between oral and intravenous steroid treatment in MS patients with acute relapse were identified through a systematic literature search. Six trials were included involving 419 participants, 210 for oral, and 209 for intravenous groups, respectively. The weighted mean differences (WMDs) in the Kurtzke’s Expanded Disability Status Scale (EDSS) score reduction between the oral and intravenous groups were 0.32 (−0.09 to 0.73);
p
= 0.129 and 0.11 (−0.12 to 0.33);
p
= 0.355 at 1 and 4 weeks after treatment, respectively. The risk ratios (RRs) for improvement by at least one EDSS point were 0.79 (0.37–1.68);
p
= 0.539 at week 1 and 0.92 (0.76–1.12);
p
= 0.400 at week 4. There were no differences in the relapse rate and relapse freedom at 6 months between groups. The WMDs in the mean percentage reduction of Gadolinium-enhancing lesions between oral and intravenous arms were 0.14 (−0.02, 0.29);
p
= 0.083 and 0.04 (−0.19, 0.28);
p
= 0.705 at 1 and 4 weeks from treatment. Among the adverse events, insomnia was significantly associated with the oral route of steroid administration RR 1.25 (1.07–1.46);
p
= 0.005. In adult patients with acute MS relapse, there were no clear-cut differences in the efficacy and overall tolerability between oral and intravenous steroids.
PDF
