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To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death.This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal.The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population.Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.

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 12months 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.

Purpose to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE). Methods a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration. Results 56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50−300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39–202; p = 0.002). No severe treatment emergent adverse events were observed. Conclusion BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.

Epileptic seizures can be triggered by specific visual stimuli, such as flickering lights and patterns. This is of special interest, considering the multitude of “real life” potential triggers, such as television and video games. The likelihood of television—and video games—induced seizures occurrence relies on several variables. Individual predisposition plays a central role. Monitor characteristics (i.e., flicker frequency, alternation rate, chromatic contrast) and content properties (i.e., brightness, emotional involvement) may also contribute to seizures occurrence in photosensitive subjects. Therefore, recommendations directed to the broadcast and TV industry have been developed in several countries, and some multinational consumer electronics and video game companies are currently financing studies on the risks deriving from visual stimulation. Environmental visual triggers include natural and artificial intermittent lights (i.e., solar rays flickering through tree leaves, discotheque stroboscopes, car headlights), and patterns (i.e., striped surfaces, escalator steps, banner advertisements). However, specific guidelines on preventive measures to limit the risks deriving from photosensitivity are lacking.

Photosensitive epilepsy is commoner in younger individuals, strongly inherited, more frequent in women, often time-limited, and closely but imperfectly related to generalised epilepsies, especially Juvenile Myoclonic Epilepsy (JME). EEG changes triggered by photic stimulation represent a useful marker of the trait. The genetics and pathophysiology of EEG photosensitivity are as yet incompletely understood but ongoing genetic searches and functional imaging studies continue to enhance our understanding. When EEG photic stimulation is carried out by utilising a consistent protocol, much more useful information is elicited than merely the presence or absence of photosensitivity. When executed carefully and consistently, quantification of the EEG photoparoxysmal response as a “Standardised Photoparoxysmal Response” (SPR) is possible. Although the SPR is non-linear, it is an ordinal single digit which quantitates the amount of photosensitivity as the “SPR”. The ability to quantitate photosensitivity then confers utility of the EEG PPR test as a predictor of likely AED efficacy and as a marker of longitudinal AED effectiveness.

Objectives: To describe how the recent lock-down, related to SARS-COV-II outbreak in Italy, affected People With Epilepsy (PwE), we designed a survey focused on subjective reactions. Using Natural Language Processing (NLP), we analyzed words PwE and People without Epilepsy (PwoE) chose to express their reactions. Methods: As a subset of a larger survey, we collected from both PwE (427) and PwoE (452) single words (one per subject) associated to the period of lock down. The survey was spread thanks to the efforts of Italian league against epilepsy Foundation during the days of maximum raise of the pandemic. Data were analyzed via bag of word and sentiment analysis techniques in R. Results: PwoE and PwE showed significantly different distribution in word choice (X2, p = 4.904e-13). A subset of subject used positive words to describe this period, subjects with positive feelings about the lock down were more represented in the PwE group (X2, p = 0.045). Conclusion: PwoE developed reactive stress response to the restrictions enacted during lock-down. PwE, instead, chose words expressing sadness and concern with their disease. PwE appear to internalize more the trauma of lock down. Interestingly PwE also expressed positive feelings about this period of isolation more frequently than PwoE. Our study gives interesting insights on how People with Epilepsy react to traumatic events, using methods that evidence features that do not emerge with psychometric scales.

Objective The objective of the study was to describe the electroclinical features, seizure semiology, and the long-term evolution of gelastic seizures (GS) not associated with hypothalamic hamartoma (HH). Methods We reviewed video-electroencephalogram (video-EEG) recordings from pediatric patients with GS without HH admitted to 14 Italian epilepsy centers from 1994 to 2013. We collected information about age at onset, seizures semiology, EEG and magnetic resonance imaging (MRI) findings, treatment, and clinical outcome in terms of seizure control after a long-term follow-up. Results A total of 30 pediatric patients were stratified into two groups according to neuroimaging findings: group 1 including 19 children (63.3%) with unremarkable neuroimaging and group 2 including 11 children with structural brain abnormalities (36.7%). At the follow-up, patients of group 1 showed better clinical outcome both in terms of seizure control and use of AED polytherapy. Our patients showed remarkable clinical heterogeneity, including seizure semiology and epilepsy severity. Electroencephalogram recordings showed abnormalities mainly in the frontal, temporal, and frontotemporal regions without relevant differences between the two groups. Overall, carbamazepine showed good efficacy to control GS. Conclusions Patients with nonlesional GS have a more favorable outcome with better drug response, less need of polytherapy, and good long-term prognosis, both in terms of seizure control and EEG findings.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

We determined whether epileptic clinical manifestations evoked by playing video games (VG) differ from those evoked by intermittent photic stimulation (IPS) or striped patterns (P). We exposed nine children who had TV- and VG-evoked seizures in daily life to 12 VG after standardized photic stimulation and pattern stimulation. Their EEGs were recorded continuously, analyzed, and then correlated with a video of their behavior. Similar types of clinical signs were seen during VG, P, and IPS, but the signs we observed were more subtle during the VG. Eight patients showed a clear lateralization. A new observation was the lowering of the eyelids to a state of half-closed. Our study suggests that the type of visual stimulus provoking a photoparoxysmal response or seizure is not particularly relevant. The children belonged to different epilepsy groups, and our findings add to the discussion on the boundaries of the epilepsy types.

Dorothee G.A. Kasteleijn-Nolst Trenite *, Linda Volkers , Eric Strengman , Herman M. Schippers , Willem Perquin , Gerrit-Jan de Haan , Anastasia O. Gkountidi , Ruben van’t Slot , Stan F. van de Graaf , Bosanka Jocic-Jakubi , Giuseppe Capovilla , Athanasios Covanis , Pasquale Parisi , Pierangelo Veggiotti , Mario Brinciotti , Gemma Incorpora , Marta Piccioli , Laura Cantonetti , Samuel F. Berkovic , Ingrid E. Scheffer , Eva H. Brilstra , Anja C.M. Sonsma , Adri J. Bader , Carolien G.F. de Kovel , Bobby P.C. Koeleman a

Purpose: To demonstrate the clinical importance of using a high quality photic stimulator for recording EEGs to diagnose photosensitivity. Methods: We performed EEG examinations on 2 adult and 2 paediatric patients with a history of visually induced seizures; routinely we used a Grass PS 40 photic stimulator (rectangular Xenon lamp giving flashes of 10 μs duration, 0.7 J, 1–30 Hz, width 7 cm, length 12 cm). We repeated the IPS with a Grass PS 33 plus stimulator (round Xenon lamp giving flashes of 10 μs duration, 1 J, 1–60 Hz, diameter 14 cm). Results: Patients were affected by both benign and catastrophic epilepsies. They complained about episodes of dizziness (case 1), dizziness accompanied by a sensation in the arms and fear (case 2), absences (case 3), and myoclonic jerks (case 4). These symptoms occurred when working with neon lights, computers or ironing striped clothes (case 1), while driving (case 2), whenever there was sunlight (case 3 and 4). Only IPS performed with the Grass PS 33 plus stimulator evoked PPRs accompanied by their typical complaints. In all cases, the revised diagnosis led to changes in their treatment and the disappearance or diminishment of their complaints and PPR range. Conclusion: A PPR can occur in various types of epilepsy, can have a different meaning, and requires a different therapeutic intervention. Only an appropriate photic stimulator with diffuse white light and a flash intensity level of 1 J/flash, can reliably demonstrate whether a patient is photosensitive, or equally important exclude it.

Migrainous headache is reported by patients with photosensitive epilepsy, whereas their relatives complain more often about headache than the relatives of patients with other types of epilepsy. We therefore investigated whether headache itself could be an epileptic symptom related to photosensitivity Four probands with headache and photosensitive epilepsy were selected. Their first-degree family members were studied using video-EEG with extensive intermittent photic stimulation and pattern stimulation. Nine of the 12 subjects (10 female and two male, mean age 30 years, range 14–46 years) proved to be photosensitive with either focal ( n = 5) or generalized ( n = 4) epileptiform discharges. In two subjects an ictal recording of headache occurred after visual stimulation. We found evidence that, in specific patients, headache could be an ictal sign of epilepsy. Photic stimulation during EEG recording can contribute to correct diagnosis and lead to the best care and management of the patient.

The comorbidity between epilepsy and migraine has been well known for a century, yet it is still not fully understood; the two disorders also share some risk factors, symptoms, and preventive drug therapy. A series of clinical observations and scientific data support the hypothesis of alteration of cortical excitability as a possible mechanism underlying their pathology, with both disorders characterized by transient paroxysmal neurological disturbance. So far, the numerous pathophysiological mechanisms responsible for neuronal hyperexcitability have only been studied in familial hemiplegic migraine (FHM), but they do suggest a link between migraine and epilepsy. Several studies support the hypothesis of a clinical continuum between some types of migraine and some types of epilepsies, with possibly even a complete overlap, representing, in particular cases, headache as the sole ictal manifestation of seizures. Taking into account the data in the literature, we hypothesize that several aetiopathological noxae (either environmental or genetics), such as Na+-K+ ATPase pump impairment, converging on a common final pathway represented by neuronal membrane hyperexcitability, could manifest as either epilepsy or headache/migraine, or both. The potential implications arising from this point of view include (a) a revision of headache/migraine diagnostic criteria as the sole ictal epileptic manifestation in international classifications of both epilepsies and headache disorders; (b) the careful follow-up of patients with headache/migraine as a residual feature, taking into consideration a revised concept of "complete seizure control" to avoid mistakes due to inopportune withdrawal of antiepileptic treatment. In addition, we suggest that headache is associated with other ictal-sensitive and motor features (more than those reported); these may be highly underestimated due to impairment of consciousness during complex partial seizures with or without secondary generalization.

We report the history of a 14-year-old girl with atypical childhood occipital epilepsy "Gastaut type" whose first generalized tonic-clonic seizure was preceded by migraine without aura and followed by a status migrainosus. This status lasted for 3 days despite standard analgesic therapy. An EEG recording revealed an occipital status epilepticus during her migraine complaints. Seven minutes after intravenous administration of 10 mg diazepam under continuous EEG recording, a suppression of the epileptiform discharges over the right occipital was seen, while the headache subsided 3 min later. After precise questioning about the circumstances that possibly could have led to these events, it appeared that she had played for hours with a play station on the new color TV and she had visited an exhibition of Matisse and Bonnard with bright colors and contrast-rich text. Standardized extensive intermittent photic stimulation (IPS), 2 days after the status migrainosus, evoked besides asymmetrical right-sided driving, green spots in her left visual field, while in the EEG sharp waves were recorded over the right parietotemporal region. After further IPS with 20 Hz (eye closure), she started complaining of a light pulsating headache right occipitally and in the EEG right parietotemporal sharp-waves were seen. This lasted for about 10 min. Later, an interictal routine EEG was normal except for some theta over the right temporooccipital area. The most likely diagnosis is an atypical form of occipital epilepsy "Gastaut type." We would therefore advocate recording EEGs with photic stimulation in patients with atypical migraneous features.