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      Clinical and Electroencephalography Assessment of the Effects of Brivaracetam in the Treatment of Drug-Resistant Focal Epilepsy

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          Abstract

          Introduction: Our aim was to evaluate the clinical and electroencephalographic effects of brivaracetam (BRV) in patients with drug-resistant focal epilepsy. BRV is a new antiepileptic drug (AED) with a high affinity for vesicle protein 2A (SV2A) and recently approved as adjunctive therapy for focal onset seizures. Methods: In this observational study of six-month duration, BRV (50-200 mg) was administered to 76 patients with drug-resistant focal epilepsy, who were ≥16-year-old and who suffered from daily, weekly, monthly and yearly recurrent seizures. At baseline and after six months of follow-up, we performed a neurological visit, neuropsychological tests: Quality of life in epilepsy-31 (QOLIE31), Epworth Sleepiness Scale (ESS), Intrapersonal Emotional Quotient (IEQ) and an electroencephalogram (EEG; inspective and quantitative analysis). Twenty-four patients underwent an overnight switch from levetiracetam (LEV) to BRV. Results: Seizure frequency of the 54 patients remaining at six months was reduced >50% in 29.6% of cases (responders), <50% in 31.5% (non-responders 1), while it remained unchanged in 38.8% (non-responders 2). Twenty-nine percent of patients early discontinued BRV because of lack of efficacy or minor adverse effects (AEs) like irritability, asthenia or headache. Neuropsychological tests in 28 patients demonstrated a significant improvement in I-EPI scores (p=0.04). Comparable results have been found in the subgroup of patients who switched from LEV to BRV. The EEG quantitative analysis showed a significant reduction of alpha absolute power at six months (p=0.03). Theta band power resulted significantly superior in non-responders than in responders (p=0.03). Furthermore, the δ+θ/α+β index resulted more elevated in patients with AEs than in patients without. Conclusions: BRV showed discrete results in terms of efficacy, safety and tolerability, with a good behavioural profile. BRV reduces the power of the alpha band, in correlation with its sedative effects but not with its minor efficacy. Furthermore, the increase in theta band power can be considered as a predictor of scarce response to treatment, while an increase in the δ+θ/α+β index could be a possible predictor of AEs occurrence.

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          Most cited references30

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          Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.

          To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
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            Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology

            The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types.
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              Drug-resistant epilepsy.

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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                13 May 2021
                May 2021
                : 13
                : 5
                : e15012
                Affiliations
                [1 ] UOC Neurologia, Ospedale Santo Bono-Pausilipon, Napoli, ITA
                [2 ] UOC Neurofisiopatologia, Policlinico Umberto I, Rome, ITA
                [3 ] Department of Human Neuroscience, Neurophysiopathology Unit, Policlinico Umberto I, Rome, ITA
                [4 ] CNAPS Department (Promotion and Evaluation of Chronic Disease Prevention Policies), Istituto Superiore di Sanità (ISS), Rome, ITA
                [5 ] Department of Human Neuroscience, Neurophysiopathology Unit, Policlinico Umberto I, University of Rome “Sapienza”, Rome, ITA
                Author notes
                Article
                10.7759/cureus.15012
                8197576
                5f32d60f-a2a9-498c-a194-8ce0826884c4
                Copyright © 2021, Savastano et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 April 2021
                Categories
                Internal Medicine
                Neurology
                Other

                brivaracetam,levetiracetam,focal drug resistant epilepsy,quantitative eeg,pharmaco-eeg,neurocognitive tests

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