The real-world effectiveness of intravenous brivaracetam as a second-line treatment in status epilepticus.

PURPOSE: Status epilepticus (SE) is defined by abnormally prolonged seizures that may lead to brain damage and death. Our aim was to evaluate the efficacy and tolerability (effectiveness) of intravenous brivaracetam (BRV) as a second-line treatment. METHODS: Twenty-one patients (median age 68 years ± 17.28) were prospectively recruited between June 2019 and December 2022. Patients were treated with BRV (50-200 mg) as a second-line add-on therapy for SE. We evaluated the response of SE to the administration of BRV in terms of SE termination and recurrence of epileptic seizures at 6, 12, and 24 h, also monitoring safety. The first-line therapy was represented by intravenous benzodiazepines (mainly diazepam). RESULTS: Almost a quarter of patients had generalized seizures, whereas the vast majority (76.2%) presented focal seizures. In 52.4% of patients, the underlying cause was cerebrovascular. Fourteen (66.7%) patients displayed a good early response in the subsequent 6 h. At 12 and 24 h, 8 (38%) and 11 (52.4%) patients, respectively, did not present seizures. CONCLUSION: The present study highlights the potential of BRV when used as an early add-on therapy in SE, further confirming its good safety profile.

Neuropsychological Evaluation and Quantitative EEG in Patients with Frontotemporal Dementia, Alzheimer's Disease, and Mild Cognitive Impairment.

This study analyzed the efficacy of EEG resting state and neuropsychological performances in discriminating patients with different forms of dementia, or mild cognitive impairment (MCI), compared with control subjects. Forty-four patients with dementia (nineteen patients with AD, and seven with FTD), eighteen with MCI, and nineteen healthy subjects, matched for age and gender, underwent an extensive neuropsychological test battery and an EEG resting state recording. Results showed greater theta activation in posterior areas in the Alzheimer's disease (AD) and Fronto-Temporal Dementia (FTD) groups compared with the MCI and control groups. AD patients also showed more delta band activity in the temporal-occipital areas than controls and MCI patients. By contrast, the alpha and beta bands did not discriminate among groups. A hierarchical clustering analysis based on neuropsychological and EEG data yielded a three-factor solution. The clusters differed for several neuropsychological measures, as well as for beta and theta bands. Neuropsychological tests were most sensitive in capturing an initial cognitive decline, while increased theta activity was uniquely associated with a substantial worsening of the clinical picture, representing a negative prognostic factor. In line with the Research Domains Framework (RDoC) perspective, the joint use of cognitive and neurophysiological data may provide converging evidence to document the evolution of cognitive skills in at-risk individuals.

A retrospective multicentric study on the effectiveness of intravenous brivaracetam in seizure clusters: Data from the Italian experience.

OBJECTIVE: Nearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. METHODS: Retrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. RESULTS: 97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 - 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 - 9.7). No severe treatment emergent adverse events were observed. SIGNIFICANCE: In our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.

Ischemic stroke and reperfusion therapies in diabetic patients.

INTRODUCTION: The study aimed to identify the main prognostic factors in diabetic patients with ischemic stroke undergoing reperfusion therapies (RT). METHODS: This retrospective study included 170 diabetic patients: 62 treated with intravenous thrombolysis (IVT) alone and 108 with mechanical thrombectomy (MT). Among MT patients, 29 underwent IVT. We collected clinical, laboratory, and radiological data. The outcomes were 3-month functional impairment (measured by modified Rankin scale, mRs), discharge neurological severity (measured by National Institutes of Health Stroke Scale score, NIHSS), 3-month mortality, intracranial hemorrhage (ICH), and symptomatic intracranial hemorrhage (SICH). We performed a general analysis for all RT and sub-group analyses for IVT and MT. RESULTS: A lower mRs was associated with lower glycemia and admission NIHSS (aNIHSS) in all RT and MT; lower aNIHSS and younger age in IVT. Mortality increased with hyperglycemia, aNIHSS, and age in all RT; age and aNIHSS in IVT; hyperglycemia and systolic pressure in MT. A lower discharge NIHSS was related with lower aNIHSS, thrombolysis, and no thrombectomy in all RT; lower aNIHSS in IVT; lower aNIHSS and thrombolysis in MT. ICH was associated with elevated aNIHSS, older age, and lower platelets in all RT; lower platelets and older age in IVT; higher aNIHSS in MT. SICH depended on longer thrombectomy duration in all RT; no metformin use in IVT; higher weight in MT. CONCLUSION: The study shed light on diabetic patients and stroke RT highlighting the protective effect of metformin in IVT and the role of glycemia, weight, and combined treatment in MT.

Ischemic Stroke and Asymptomatic Pulmonary Opacities.

PURPOSE: Pulmonary opacities are described in many chest radiograph reports in stroke patients and are often asymptomatic. The aim of this study is to investigate the clinical features associated with asymptomatic pulmonary opacities (APO) and evaluate APO prognostic value in ischemic stroke. METHODS: We prospectively analyzed patients with acute ischemic stroke without pneumonia symptoms referred to our stroke center. All patients underwent a chest x-ray within 48 hours after admission. We divided patients with APO (defined as asymptomatic area of increased pulmonary attenuation) and patients without APO. Firstly, we compared clinical, laboratory, and echocardiographic parameters between groups; secondly, APO were evaluated as a possible predictor of the neurological severity at discharge and functional outcome at 90 days. RESULTS: We included 162 patients, 78 of whom had APO. On univariate analysis, we observed a significant difference between patients with APO and patients without APO in terms of neutrophils (73,56±10,10 vs 69,72±12,29; p=0,031), atrial fibrillation (AF, paroxysmal 27,4% vs 25,6%; permanent 19% vs 2,6%; p<0,002), cardioembolic etiology (37,2% vs 22,7%, p <0,033), thrombectomy (58,3% vs 42,9%, p <0,05), dysphagia/vomit (34,5% vs 14,10%, p<0,005), admission NIHSS (14,20±5,98 vs 10,29±5,82, p=0,001), discharge NIHSS (8,68±6,73 vs 5,64±6,20; p=0,003), and 90 days mRS (3,47±2,12 vs 2,31±1,93; p=0,001). On multivariate analysis, APO were significantly associated with admission NIHSS and AF. APO were a predictor of outcome on univariate analysis, but not on multivariate. CONCLUSION: APO in acute ischemic stroke are associated with AF. APO were not a predictor of neurological and functional outcome.

Prevalence of prothrombotic polymorphisms in a selected cohort of cryptogenic and noncryptogenic ischemic stroke patients.

Ischemic stroke is a complex multifactorial disease and approximately 30%, especially in the young, are cryptogenic. In some of the patients with cryptogenic ischemic stroke the underlying risk factor may be a prothrombotic state. We studied 101 patients with ischemic stroke under 55 years of age. All the patients underwent an extensive diagnostic evaluation to determine the cause of stroke. Common variations in the genes encoding factor V, prothrombin, 5,10-methylenetetrahydrofolate reductase, plasminogen activator inhibitor-1, and human platelet alloantigens-1 were evaluated. Of the 101 patients with ischemic stroke, 28 patients had cryptogenic ischemic stroke. At least one of the different genetic polymorphisms investigated was present in 44% patients in the total group and in 48% of patients with cryptogenic ischemic stroke. In this study population under 55 years of age there was no significant difference in the prevalence of various genetic polymorphisms, factor V, prothrombin, 5,10-methylenetetrahydrofolate reductase, plasminogen activator inhibitor-1, and human platelet alloantigens) in patients with cryptogenic ischemic stroke and in patients with ischemic stroke of determined cause.

Brainstem ischemia, steno-occlusive pathology of the vertebral arteries, and alterations in the circadian blood pressure pattern: a case report.

We report the case of a patient with vertebrobasilar steno-occlusive pathology associated with ischemic brainstem symptomatic lesions related to abnormal decrease in blood pressure (BP). A 63-year-old man presented vertigo and persistent gait impairment as a result of a posterior cerebellar infarction and, during hospitalization, experienced a new episode of cerebral ischemia in the territory of the anterior cerebellar artery. Cerebral angiography showed occlusion of the left vertebral artery and two severe stenoses of the right vertebral artery, and 24-hour dynamic BP monitoring evidenced severe postprandial hypotension. Medical treatment was not effective so he underwent an endovascular procedure. This report documents the importance of BP monitoring for a better understanding of the pathophysiology of posterior ischemic strokes and, above all, for a more reliable prognosis and therapy.