Claudia Cagnetti

Cerebral hemodynamics and cognitive performance in patients with asymptomatic carotid stenosis

Objective: The aim of this study was to investigate whether the presence of severe internal carotid artery stenosis may be associated with different cognitive performance in relation to the side of the stenosis and its hemodynamic consequences. Methods: Eighty-three patients with asymptomatic severe unilateral internal carotid stenosis were included. A neuropsychological investigation including Verbal Fluency using phonemic and category access, Coloured Progressive Matrices, and Complex Figure Test Copy was performed. Each patient underwent an assessment of cerebrovascular reactivity (CVR) to hypercapnia with transcranial Doppler ultrasonography using the breath-holding index (BHI). Thirty healthy subjects comparable for demographic characteristics and vascular risk profile served as controls. Subjects with carotid stenosis were classified into two groups: preserved CVR (BHI ≥0.69), 48 patients (25 with left and 23 with right stenosis); and impaired CVR (BHI <0.69), 35 patients (19 with left and 16 with right stenosis). Results: Subjects with left stenosis and reduced CVR had significantly lower performances at phonemic verbal fluency with respect to controls and the other groups of stenosis. In subjects with right stenosis and reduced CVR, scores obtained in Coloured Progressive Matrices and in Complex Figure Test Copy were significantly lower with respect to the other groups. Conclusions: These results suggest that an alteration of cerebrovascular reactivity may be responsible for reduction in some cognitive abilities involving the function of the hemisphere ipsilateral to carotid stenosis. Such findings may be of interest for providing a more comprehensive indication to surgical treatment in subgroups of subjects with asymptomatic carotid stenosis.

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.

Vascular Impairment in Alzheimer's Disease: The Role of Obstructive Sleep Apnea

Epidemiological studies have suggested a pathophysiological link between obstructive sleep apnea syndrome (OSAS) and Alzheimers disease (AD). The mechanism by which sleep disturbance can affect cognitive impairment is not clear. The aim of this study was to investigate whether AD patients with OSAS have an impairment in cerebrovascular disease markers. We included 69 patients without OSAS and 93 patients with OSAS. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). Pathological values of IMT and BHI were significantly associated with the presence of OSAS (IMT > 1.0 mm: OR 2.98, 95%CI: 1.37-6.46; p < 0.05; BHI < 0.69: OR 5.25, 95%CI: 2.35-11.74; p < 0.05, multivariate adjusted analysis). Furthermore, the extent of cerebrovascular impairment was correlated with the severity of OSAS. The finding of alterations of cerebral vessel functional and anatomic status in AD patients with OSAS suggests the potential for effective treatment for sleep-related disturbances in a subgroup of AD patients.

Carotid wall thickness and stroke risk in patients with asymptomatic internal carotid stenosis.

OBJECTIVE Aim of this study was to investigate if the risk of stroke and other vascular diseases can be predicted in subjects with severe asymptomatic carotid artery stenosis on the basis of carotid wall thickness evaluation. METHODS We included 162 consecutive subjects with asymptomatic internal carotid artery stenosis of 60% or greater reduction in diameter. Demographic characteristics, vascular risk factors, therapy, degree of carotid stenosis and carotid intima-media thickness (IMT) were detailed for all subjects. Subjects were prospectively evaluated for a median period of 35 months (min=10, max=47). Outcome measures were: the occurrence of ischemic stroke ipsilateral to carotid stenosis and any other vascular event. RESULTS Thirty subjects (18.5%) suffered a vascular event: 16 (53%) myocardial infarctions and 14 (47%) strokes. Older age and higher IMT values were the only factors significantly associated with the risk of vascular events. The hazard ratio (adjusted for age, sex and other risk factors) for each 0.1 mm of IMT increase resulted 1.30 (95% CI: 1.14, 1.18) for combined vascular events, 1.47 for cerebrovascular events (95% CI: 1.16, 1.87) and 1.24 (95% CI: 1.09, 1.42) for cardiovascular events. Values of IMT above 1.15 mm increased the risk of having a stroke 19 times and the risk of having a myocardial infarction two times. CONCLUSIONS An increased carotid wall thickness can be considered as a marker of an increased risk of vascular events in asymptomatic subjects with internal carotid artery stenosis>60%. Highest IMT values are able to identify subjects with specific stroke risk. This information could be of interest to recognize subjects who might benefit most from surgical or revascularization procedures.

Lacosamide monotherapy for partial onset seizures

PURPOSE To evaluate the 1-year efficacy and safety of oral lacosamide as conversion monotherapy in adult patients with partial onset seizures with or without generalization. METHOD We prospectively followed-up consecutive patients converted to lacosamide monotherapy after 1-year seizure freedom on lacosamide add-on therapy and withdrawal of the concurrent antiepileptic drug (AED). Seizure occurrence, treatment compliance and drug toxicity were assessed every 3 months up to 1 year. The study outcomes were the retention rate of lacosamide as single AED and the seizure freedom under lacosamide monotherapy at 1 year from withdrawal of background AED. The safety variable was the prevalence of lacosamide related adverse events (AEs). RESULTS Among the 58 included patients, at 1 year from withdrawal of background medication, 37 (63.8%) retained lacosamide as single AED and 32 (55.2%) were free from seizure occurrence under lacosamide monotherapy throughout the entire follow-up. The history of less than three lifetime AEDs turned out to be significant predictor of seizure freedom (adjusted OR = 6.38, 95% CI 1.85-21.98, p = 0.003). Twelve (20.8%) subjects reported mild to moderate AEs, with the commonest being drowsiness, dizziness, and headache. CONCLUSION Conversion to lacosamide monotherapy could be effective and well tolerated in selected adults patients with partial onset seizures who had achieved seizure freedom during lacosamide add-on therapy.

Neutrophil-to-lymphocyte ratio and neurological deterioration following acute cerebral hemorrhage

Immunity plays key roles in pathophysiology of intracerebral hemorrhage (ICH). The aim of the study was to determine whether the peripheral leukocyte count and neutrophil-to-lymphocyte ratio (NLR) predicted neurological deterioration (ND) after ICH. We identified consecutive patients with ICH who had blood sampling performed within 24 hours from symptoms onset. Total white blood cells (WBC), absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were retrieved, and the NLR computed as the ratio of the ANC to ALC values. The study endpoint was the occurrence of neurological deterioration (ND) within 7 days after ICH. One hundred ninety-two subjects were enrolled, whose 54 (28.1%) presented ND. At multivariate analysis, the WBC (adjusted odd ratio [adjOR] for 1,000 leukocytes increase 1.29, 95% confidence interval [CI] 1.11-1.50), ANC (adjOR for 1,000 neutrophils increase 1.61, 95% CI 1.30-1.99), ALC (adjOR for 1,000 lymphocytes increase 0.21, 95% CI 0.09-0.49) and NLR (adjOR for 1-point increase 1.65, 95% CI 1.36-2.00) were independently associated with ND (p≤0.001). The NLR resulted the best discriminating variable for the occurrence of the adverse outcome (area under the curve 0.888, 95% CI 0.832-0.945; p < 0.001). The NLR predicted ND after acute ICH and can aid in the risk stratification of patients.Immunity plays key roles in pathophysiology of intracerebral hemorrhage (ICH). The aim of the study was to determine whether the peripheral leukocyte count and neutrophil-to-lymphocyte ratio (NLR) predicted neurological deterioration (ND) after ICH. We identified consecutive patients with ICH who had blood sampling performed within 24 hours from symptoms onset. Total white blood cells (WBC), absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were retrieved, and the NLR computed as the ratio of the ANC to ALC values. The study endpoint was the occurrence of neurological deterioration (ND) within 7 days after ICH. One hundred ninety-two subjects were enrolled, whose 54 (28.1%) presented ND. At multivariate analysis, the WBC (adjusted odd ratio [adjOR] for 1,000 leukocytes increase 1.29, 95% confidence interval [CI] 1.11-1.50), ANC (adjOR for 1,000 neutrophils increase 1.61, 95% CI 1.30-1.99), ALC (adjOR for 1,000 lymphocytes increase 0.21, 95% CI 0.09-0.49) and NLR (adjOR for 1-point increase 1.65, 95% CI 1.36-2.00) were independently associated with ND (p≤0.001). The NLR resulted the best discriminating variable for the occurrence of the adverse outcome (area under the curve 0.888, 95% CI 0.832-0.945; p < 0.001). The NLR predicted ND after acute ICH and can aid in the risk stratification of patients.