Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures.

BACKGROUND: The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). OBJECTIVE: We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. METHODS: Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). RESULTS: Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. CONCLUSIONS: The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence.

Clinical phenotypes of embolic strokes of undetermined source.

BACKGROUND AND PURPOSE: The embolic stroke of undetermined source (ESUS) represents a heterogeneous clinical entity. The aim of this study was to investigate whether distinct clinical phenotypes may be identified in the ESUS population. METHODS: We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria. Baseline characteristics and diagnostic workup findings were collected. Hierarchical cluster analysis was carried out to classify clinical features and identify different groups of ESUS patients. RESULTS: One hundred twenty-seven patients with a mean age of 68.6 (12.5) years were included. Three main clusters were identified. The first cluster associated young age, male sex, presence of patent foramen ovale, and posterior circulation infarct. The second phenotype linked hypertension, severe stroke, left atrial cardiopathy, diabetes mellitus, and involvement of multiple vascular territories. The third cluster gathered smoking, dyslipidemia, ipsilateral vulnerable sub-stenotic carotid plaque, and infarct of anterior vascular territory. CONCLUSIONS: Distinct clinical phenotypes have been identified within the ESUS population, which may supply clues to the underlying pathogenic mechanisms.

Prediction of Outcome in Embolic Strokes of Undetermined Source.

BACKGROUND AND AIM: Predicting outcome after stroke is a major goal and research field. The Embolic Stroke of Undetermined Source (ESUS) is a recently introduced clinical construct, and the prediction of outcome in this population has to be further explored. The aim of the study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in patients with ESUS. METHODS: Consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria were identified and the ASTRAL scores estimated. The study endpoint was the 3-month unfavorable outcome (modified Rankin Scale>2). Predictive performance was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Among 202 patients with ESUS, 67 (33.2%) had unfavourable 3-month outcome. The ASTRAL score was an independent predictor of poor outcome [adjOR = 1.44, 95% confidence interval (CI) 1.30-1.60, P < .001], showed good discriminatory power (area under the receiver operating characteristic curve .913, 95% CI .871-.956) and was well calibrated (Hosmer-Lemeshow test P = .496). CONCLUSIONS: The ASTRAL score was an independent predictor of 3-month functional outcome and showed high predictive accuracy in patients with ESUS.

Erenumab for Preventive Treatment of Migraine: A Systematic Review and Meta-Analysis of Efficacy and Safety.

BACKGROUND: Novel therapeutic options with improved efficacy and safety profiles are needed for the prophylaxis of migraine. In recent years, the inhibition of calcitonin gene-related peptide (CGRP) signaling has attracted growing interest in the pharmacological research on migraine. Erenumab is the first fully human monoclonal antibody directed against the CGRP receptor to be approved for use in migraineurs. OBJECTIVE: To evaluate the efficacy and safety of erenumab as preventive treatment in patients with migraine using meta-analytical techniques. METHODS: Randomized, placebo-controlled, single- or double-blinded trials were identified through a systematic literature search (October week 4, 2018). Main outcomes included the changes from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD) at week 12, and the incidence of adverse events (AEs), severe AEs (SAEs) and treatment withdrawal due to AEs. Mean difference (MD) and risk ratio (RR) with 95% confidence intervals (95% CIs) were estimated. RESULTS: Across the five included trials, erenumab given as a subcutaneous injection at a monthly dosage of 70 mg and 140 mg was associated with a significantly greater reduction in baseline MMD (70 mg: MD - 1.3, 95% CI - 1.7 to - 1.0, p < 0.001; 140 mg: MD - 1.9, 95% CI - 2.3 to - 1.4, p < 0.001) and MSMD (70 mg: MD - 1.0, 95% CI - 1.6 to - 0.4, p < 0.001; 140 mg: MD - 1.8, 95% CI - 2.5 to - 1.1, p < 0.001) than placebo. There were no differences in the occurrence of AEs, SAEs, and drug withdrawal due to AEs between the erenumab and placebo groups. CONCLUSIONS: Erenumab is an efficacious and well tolerated preventive treatment in adult patients with episodic and chronic migraine.

Endovascular treatment of symptomatic vertebral artery stenosis: A systematic review and meta-analysis.

BACKGROUND: The study aim was to evaluate the safety and efficacy of endovascular treatment (EVT) versus medical treatment (MT) in patients with symptomatic vertebral artery (VA) stenosis. METHODS: Randomized controlled trials with active and control groups receiving EVT plus MT and MT alone in patients with vertebro-basilar transient ischemic attack (TIA) or stroke and VA stenosis were identified. Primary endpoints included the occurrence of any stroke, any vertebro-basilar stroke, vertebro-basilar ischemic stroke, and vertebro-basilar TIA. Secondary endpoints were myocardial infarction, vascular death, and composite vascular outcome. All endpoints were assessed at short and long-term. Risk ratios (RRs) with 95% confidence intervals (CIs) have been estimated. RESULTS: Four trials were included involving 370 participants, 194 and 176 for EVT and MT arms, respectively. There was no overall effect of EVT on the occurrence of any stroke [short-term: RR 3.05 (95% CI 0.33-28.49); long-term: RR 0.75 (95% CI 0.40-1.40)], any vertebro-basilar stroke [short-term RR 3.05 (95% CI 0.33-28.49); long-term RR 0.91 (95% CI 0.42-1.99)], vertebro-basilar ischemic stroke [short-term: RR 1.02 (95% CI 0.07-15.88); long-term RR 1.27 (95% CI 0.36-4.50)], vertebro-basilar TIA [short-term: RR 5.00 (95% CI 0.28-90.18); long-term: RR 0.85 (95% CI 0.39-1.81)]. There were no differences across the treatments in any secondary outcome. CONCLUSIONS: There were no clear-cut benefits or harms for EVT versus MT alone in patients with symptomatic VA stenosis.