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

Sporadic Fatal Insomnia in Europe:Phenotypic features and diagnostic challenges

[Objective] Comprehensively describe the phenotypic spectrum of sporadic fatal insomnia (sFI) to facilitate diagnosis and management of this rare and peculiar prion disorder.[Methods] A survey among major prion disease reference centers in Europe identified 13 patients diagnosed with sFI in the past 20 years. We undertook a detailed analysis of clinical and histopathological features and the results of diagnostic investigations.[Results] Mean age at onset was 43 years, and mean disease duration 30 months. Early clinical findings included psychiatric, sleep, and oculomotor disturbances, followed by cognitive decline and postural instability. In all tested patients, video‐polysomnography demonstrated a severe reduction of total sleep time and/or a disorganized sleep. Cerebrospinal fluid (CSF) levels of proteins 14‐3‐3 and t‐tau were unrevealing, the concentration of neurofilament light protein (NfL) was more consistently increased, and the real‐time quaking‐induced conversion assay (RT‐QuIC) revealed a positive prion seeding activity in 60% of cases. Electroencephalography and magnetic resonance imaging showed nonspecific findings, whereas fluorodeoxyglucose positron emission tomography (FDG‐PET) demonstrated a profound bilateral thalamic hypometabolism in 71% of cases. Molecular analyses revealed PrPSc type 2 and methionine homozygosity at PRNP codon 129 in all cases.[Interpretation] sFI is a disease of young or middle‐aged adults, which is difficult to reconcile with the hypothesis of a spontaneous etiology related to stochastic, age‐related PrP misfolding. The combination of psychiatric and/or sleep‐related symptoms with oculomotor abnormalities represents an early peculiar clinical feature of sFI to be valued in the differential diagnosis. Video‐polysomnography, FDG‐PET, and especially CSF prion RT‐QuIC and NfL constitute the most promising supportive diagnostic tests in vivo.Peer reviewe

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

Treatment of narcolepsy

Narcolepsy is a neurological disorder characterized, in its classical form, by excessive daytime sleepiness (EDS) with irresistible episodes of sleep, cataplexy, disrupted nocturnal sleep, hypnagogic/hypnopompic hallucinations and sleep paralysis. It is often under-diagnosed, however, if it is suitably diagnosed, symptoms can be well treated by means of targeted drugs, such as modafinil to treat EDS, sodium oxybate for cataplexy, as well as EDS and disrupted nocturnal sleep, and tricyclic and newer antidepressants for cataplexy. Hallucinations and sleep paralysis can be treated with the same drugs used for cataplexy. Amphetamines and amphetamine-like stimulants are used less nowadays. Behavioral measures are also important and useful. The discovery of hypocretin deficiency in narcoleptic patients opens new perspectives for the development of newer therapeutic approaches for both EDS and cataplexy. Therapy for narcolepsy is chronic, hence symptomatic. However, the correct use of available drugs enables patients to gain a better quality of life, keeping the symptoms under control, which, mainly from a social point of view, are heavily disabling. \ua9 2009 Expert Reviews Ltd

The treatment of narcolepsy

Narcolepsy is a sleep disorder characterized, in its classical form, by excessive daytime sleepiness (EDS) with irresistible episodes of sleep, cataplexy, disrupted nocturnal sleep, hypnagogic/hypnopompic hallucinations and sleep paralysis. It is often underdiagnosed, but if it is suitably diagnosed, symptoms can be well treated by means of targeted drugs, such as: 1) modafinil, to treat EDS; 2) sodium oxybate, for cataplexy, but also for EDS and disrupted nocturnal sleep; 3) tricyclic and newer antidepressants, for cataplexy. Hallucinations and sleep paralysis can be treated with the same drugs used for cataplexy. Amphetamines and amphetamine-like stimulants are less prescribed nowadays. Behavioural measures are also important and useful. The discovery of hypocretin deficiency in narcoleptic patients opens new perspectives for the development of new therapeutic approaches for both EDS and cataplexy. Therapy for narcolepsy is chronic, hence symptomatic. However, a correct use of available drugs enables patients gaining a better quality of life, keeping under control the symptoms, that are heavily disabling, mainly from the social point of view

The fusiform gyrus and theory of mind: a case study

INGLES

18 F-FDG in the presurgical evaluation of epilepsies : a pictorial essay

Among the therapeutic options of drug-resistant focal epilepsies, surgical treatment is the most effective treatment, provided that the location of the epileptogenic area is identified. Among the imaging modalities, MRI represents the fundamental method for the identification of structural lesions. However, despite the continuous technical progress of the equipment, a significant proportion of patients do not present recognizable alterations with MRI. PET with 18 F-FDG is a method of investigation of cerebral metabolism and can be useful to identify the epileptogenic area and the extension of the epileptogenic network. In this pictorial essay, the role of PET is briefly reported and some representative clinical cases presented. In epilepsies of the mesial temporal lobe, PET is useful for confirming the laterality of the epileptogenic area and for confirming the cases of bi-temporal epilepsy, in which surgery is contraindicated, as well as to recognize remote areas of altered metabolism that could change the planning of surgery. In extra-temporal focal epilepsies, 18 F-FDG PET can detect focal metabolism alterations indicative of lesions such as focal cortical dysplasia, even when the MRI is negative.However, for the correct interpretation of 18 F-FDG, MRI is necessary. With the use of PET/MRI hybrid devices, the best accuracy of PET is obtained, but the use of registration softwares is, however, suitable for the purpose of accurately identifying the cerebral cortex and avoiding errors in the interpretation of PET. The text describes the protocol for acquiring and recording MRI and 18 F-FDG images for clinical use in use in our Department of Pre-surgical Diagnostics