Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure\u2010freedom, seizure response ( 65 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45 years (33\u201356) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for 65 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). Conclusion: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32–56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45 years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). Conclusion: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations

Predictive value of high titer of GAD65 antibodies in a case of limbic encephalitis

We report the case of a 42-year-old woman who presented with vertigo and migraine and rapidly developed cognitive decline and seizures. Both serum and cerebro-spinal fluid samples showed high titer of anti-glutamic acid decarboxylase (anti-GAD65) antibodies (998,881 IU/ml and 54,687 IU/ml respectively). Limbic encephalitis was diagnosed and high dose steroids treatment started. During one-year follow-up, without further immunomodulatory therapy, the patient became seizure free, and cognitive functions returned to normal. Serum anti-GAD65 antibodies titer decreased significantly but remained elevated (192,680 IU/ml). We discuss the prognostic and pathogenic value of high titer anti-GAD65 antibodies and its variations in a case of autoimmune limbic encephalitis

Intraoperative ultrasonography (ioUS) characteristics of focal cortical dysplasia (FCD) type II b

Purpose: Focal cortical dysplasia (FCD) is one of the major causes of drug-resistant epilepsy. Surgery has proved to be the treatment of choice, however up to a third of patients experience only partial resection. Ill-defined borders and lesions embedded in eloquent areas are two of the main drawbacks of FCD surgery. Preliminary experiences with intraoperative ultrasound (ioUS) have proved its feasibility and potential. We analyzed FCD\u2019 ioUS findings in our patients with FCD and compared them with magnetic resonance (MRI) ones. Methods: We retrospectively reviewed all records of patients with focal medically refractory epilepsy who underwent ioUS guided surgery between November 2014 and October 2017. Lesions other than FCD or FCD associated with other pathological entities were not considered. Patients\u2019 preoperative MRI and ioUS features were analyzed according to up-to-date literature and than compared. Results: A homogeneous population of five patients with type IIb FCD was evaluated. Focal cortical thickening and cortical ribbon hyper-intensity, blurring of the grey-white matter junction and hyper-intensity of the subcortical white matter on T2-weighted/FLAIR images were present in all patients. Cortical features had a complete concordance between ioUS and MRI. In particular ioUS thickening and hyper-echogenicity of cortical ribbon were identified in all cases (100%). Contrary, hyper-echoic subcortical white matter was detected in 60% of the patients. IoUS images resulted in clearer lesion borders than MRI images. Conclusion: Our study confirms the potentials of ioUS as a valuable diagnostic tool to guide FCD surgeries

Bitemporal epilepsy : a specific anatomo-electro-clinical phenotype in the temporal lobe epilepsy spectrum

Purpose: Temporal lobe epilepsy (TLE) with bilateral ictal involvement (bitemporal epilepsy, BTLE) is an intriguing form of TLE whose characteristics need to be carefully identified as BTLE patients are not good surgical candidates. The purpose of this study was to define the anatomo-electro-clinical features differentiating BTLE from unilateral TLE (UTLE). Methods: Forty-eight BTLE patients underwent long-term video-EEG monitoring (VEEG) and experienced seizures with bilateral temporal lobe involvement. Their main electro-clinical (demographics, interictal and ictal EEG, ictal signs) and neuro-imaging [brain magnetic resonance imaging (MRI)] data were compared with those of a group of 38 UTLE patients. Results: In comparison with the UTLE patients, the BTLE cohort was significantly older at the time of epilepsy onset (p = 0.023), more frequently experienced bilateral asynchronous interictal epileptiform discharges during wakefulness (p = 0.001) and sleep (p < 0.001), bilateral upper limb dystonia (p = 0.005), and auditory auras (p = 0.027), and less frequently showed a recognisable initial ictal EEG pattern of focal flattening or low-voltage fast activity (p < 0.001), post-ictal memory of seizures (p = 0.001), staring (p <0.001), head deviation (p = 0.004), oro-alimentary automatisms (p = 0.006), and positive brain MRI (p < 0.001). MRI revealed neoplastic lesions (p = 0.007) or alterations other than hippocampal sclerosis (p = 0.028) only in the UTLE patients. Conclusion: The possibility of recognising BTLE patients during pre-surgical evaluation or being able to suspect bitemporal seizures before VEEG by identifying particular anatomo-electro-clinical patterns is diagnostically important for epileptologists and can help to prevent possible surgical failures