Search

Although the prevalence of headache in the elderly is relevant, until now few studies have been conducted in patients over the age of 65 years. We analyzed the clinical charts of 4,417 consecutive patients referred to our Headache Centre from 1995 to 2002. There were 282 patients over 65 years of age at the first visit, corresponding to 6.4% of the study population. Primary headaches were diagnosed in 81.6% of the cases, while secondary headaches and non-classifiable headaches represented, respectively, 14.9% and 3.5% of the cases. Among primary headaches, the prevalence was almost the same for migraine without aura (27.8%), transformed migraine (26.1%) and chronic tension-type headache (25.7%). The most frequent secondary headaches were trigeminal neuralgia and headache associated with cervical spine disorder. [ABSTRACT FROM AUTHOR]

Many drugs are now available for treating migraine attacks, including agents specifically indicated for this condition. Since 1990 sumatriptan, the first 5-HTJBJD receptor agonist, was introduced and realized a real breakthrough in therapy; other agents of this class of drugs called triptans have more recently been used. All of them are effective in relieving the symptoms of migraine, but each exhibits pharmacological and/or clinical features that must be considered for the optimal care and management of the patient. We present here a short overview on the main clinical features of the triptans already in use in Italy. [ABSTRACT FROM AUTHOR]

Among the primary headaches, cluster headache (CH) presents very particular features allowing a relatively easy diagnosis based on criteria listed in Chapter 3 of the International Classification of Headache Disorders (ICHD-II). However, as in all primary headaches, possible underlying causal conditions must be excluded to rule out a secondary cluster-like headache (CLH). The observation of some cases with clinical features mimicking primary CH, but of secondary origin, led us to perform an extended review of CLH reports in the literature. We identified 156 CLH cases published from 1975 to 2008. The more frequent pathologies in association with CLH were the vascular ones (38.5%, n¼ 57), followed by tumours (25.7%, n¼ 38) and inflammatory infectious diseases (13.5%, n¼ 20). Eighty were excluded from further analysis, because of inadequate information. The remaining 76 were divided into two groups: those that satisfied the ICHD-II diagnostic criteria for CH, ‘fulfilling’ group (F), n¼ 38; and those with a symptomatology in disagreement with one or more ICHD-II criteria, ‘not fulfilling’ group (NF), n¼ 38. Among the aims of this study was the possible identification of clinical features leading to the suspicion of a symptomatic origin. In the differential diagnosis with CH, red flags resulted both for F and NF, older age at onset; for NF, abnormal neurological/general examination (73.6%), duration (34.2%), frequency (15.8%) and localization (10.5%) of the attacks. We stress the fact that, on first observation, 50% of CLH presented as F cases, perfectly mimicking CH. Therefore, the importance of accurate, clinical evaluation and of neuroimaging cannot be overestimated. [ABSTRACT FROM AUTHOR]

Presents abstracts of several studies on cluster headache. 'Cluster headache without pain,' by I. Pavao-Martins, R. Gil-Gouveia and J. Joao-Lobo-Antunes; 'Hemicrania continua with contralateral episodic cluster headache: a case report,' by C. Lisotto, F. Dainese and F. Maggioni; 'Pain-relieving measures and behaviour during cluster headache attacks,' by E.P. Parreira, A. Tome, R.G. Gouveia and I.P. Martins.

Objectives: An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods., Materials: Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC)., Methods: EEG data were investigated from two different angles: frequency domain-spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain-FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups., Results: The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p  < 0.01 and DR-t2 vs. HC, p  < 0.01). The θ power differed between DR-t1 and DR-t2 ( p  = 0.015) and between DR-t1 and HC ( p  = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p  < 0.01 and DR-t2 vs. HC, p  < 0.01). The IAF value was lower for DR-t1 than DR-t2 ( p  = 0.048) and HC ( p  = 0.042). The FD value was lower in DR-t1 than in DR-t2 ( p  = 0.015) and HC ( p  = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ., Discussion: FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes., Conclusion: Our work suggests that FD is a promising measure to monitor the response to ASMs in FE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Porcaro, Seppi, Pellegrino, Dainese, Kassabian, Pellegrino, De Nardi, Grego, Corbetta and Ferreri.)

Introduction: The study aimed to evaluate the effectiveness and safety of brivaracetam (BRV) as conversion monotherapy in adults with focal epilepsy treated in the context of real-world clinical practice., Methods: This was a retrospective, observational, non-interventional study in adults with focal epilepsy who converted to BRV monotherapy following the withdrawal of background antiseizure medications (ASMs). Primary effectiveness outcome was the retention rate of BRV as single ASM at 6 and 12 months. Secondary outcomes included the 6- and 12-month rates of seizure freedom. Safety and tolerability outcomes included the frequency and type of adverse events (AEs) and the occurrence of treatment discontinuation due to AEs., Results: A total of 44 participants with a median age of 63.5 (interquartile range 44-73.5) years were included; 17 subjects were seizure free at baseline, and 9 of them switched from levetiracetam because of lack of tolerability. The retention rate of BRV monotherapy was 88.6% (39/44) at 6 months and 83.9% (26/31) at 12 months. The rates of seizure freedom were 72.7% (32/44) in subjects with 6-month follow-up and 58.1% (18/31) in subjects with 12-month follow-up. The median maintenance dosage of BRV monotherapy was 150 (100-200) mg/day at 6 months and 125 (100-200) mg/day in subjects with 12-month follow-up. Adverse events were recorded in 6/44 (13.6%) participants and led to BRV discontinuation in 2/44 (4.5%) cases. The reported AEs were somnolence (n = 3), fatigue (n = 2), and irritability (n = 1); no serious AEs were experienced. In 21/44 (47.7%) participants, BRV monotherapy resulted from the direct switch from levetiracetam. The rates of treatment retention and seizure freedom at 6 and 12 months were higher among people who switched from levetiracetam to BRV monotherapy., Conclusion: Brivaracetam may be a valuable treatment of focal seizures in people who converted to monotherapy in a real-life setting., (© 2024. The Author(s).)

Objective: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives., Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models., Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM., Significance: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug-resistant focal epilepsy., Methods: Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6-month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment-related variables were assessed by using a stepwise logistic regression model., Results: At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re-assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow-up, whereas no association was identified with sociodemographic and epilepsy-related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6-month re-assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two-fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes., Significance: Almost 1 in 5 adults with drug-resistant focal epilepsy who screen negative for depression become positive when re-assessed 6 months after a treatment change. At re-assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline., (© 2023 International League Against Epilepsy.)

Objective: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST)., Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5-20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6., Results: A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5-20, and >20 seizures per month (p < .001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p < .001). SSR was reached by 51.2% and 26.5% participants with a history of 1-5 and ≥6 ASMs (p < .001); the corresponding rates of SSF were 24.7% and 4.5% (p < .001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p < .001), and in participants with history of ≥6 prior ASMs compared to those with history of 1-5 ASMs (19.6% vs. 12.2%, p = .002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs., Significance: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Subcortical band heterotopia (SBH) is a rare malformation of the cortical development characterized by a heterotopic band of gray matter between cortex and ventricles. The clinical presentation typically includes intellectual disability and epilepsy., Purpose: To evaluate if the Extended Glasgow Outcome Scale-pediatric version (EGOS-ped) is a feasible tool for evaluating the functional disability of patients with (SBH)., Method: Cross-sectional multicenter study of a cohort of 49 patients with SBH (female n = 30, 61%), recruited from 23 Italian centers., Results: Thirty-nine of 49 (80%) cases showed high functional disability at EGOS-ped assessment. In the poor result subgroup (EGOS-ped >3) motor deficit, language impairment, and lower intelligence quotient were more frequent (P < 0.001, P = 0.02, and P = 0.01, respectively); the age at epilepsy onset was remarkably lower (P < 0.001); and the prevalence of epileptic encephalopathy (West syndrome or Lennox-Gastaut-like encephalopathy) was higher (P = 0.04). The thickness and the extension of the heterotopic band were associated with EGOS-ped score (P < 0.01 and P = 0.02). Pachygyria was found exclusively among patients with poor outcome (P < 0.01)., Conclusions: The EGOS-ped proved to be a reliable tool for stratifying the functional disability of patients with SBH. According to this score, patients could be dichotomized: group 1 (80%) is characterized by a poor overall functionality with early epilepsy onset, thick heterotopic band, and pachygyria, whereas group 2 (20%) is characterized by a good overall functionality with later epilepsy onset and thinner heterotopic band., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST)., Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained 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. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications., Results: A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p < 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p < 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p < 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively., Conclusion: Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy., (© 2022. The Author(s).)

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., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

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., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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 <65 years ('younger')., Results: There were 1029 patients with focal epilepsy included in the study, of whom 111 (10.8%) were aged ≥65 years. The median daily dose of brivaracetam at 3 months was 100 [interquartile range, 100-175] mg in the older group and 100 [100-200] mg in the younger group (p = 0.036); it was 150 [100-200] mg in both groups either at 6 months (p = 0.095) or 12 months (p = 0.140). At 12 months, 49 (44.1%) older and 334 (36.4%) younger patients had a reduction in their baseline seizure frequency by at least 50% (p = 0.110), and the seizure freedom rates were 35/111 (31.5%) and 134/918 (14.6%) in older and younger groups, respectively (p < 0.001). During the 1-year study period, 20 (18.0%) patients in the older group and 245 (26.7%) patients in the younger group discontinued brivaracetam (p = 0.048). Treatment withdrawal because of insufficient efficacy was less common in older than younger patients [older: n = 7 (6.3%), younger: n = 152 (16.6%); p = 0.005]. Adverse events were reported by 24.2% of older patients and 30.8% of younger patients (p = 0.185); the most common adverse events were somnolence, nervousness and/or agitation, vertigo, and fatigue in both study groups., Conclusions: Adjunctive brivaracetam was efficacious, had good tolerability, and no new or unexpected safety signals emerged when used to treat older patients with uncontrolled focal seizures in clinical practice. Adjunctive brivaracetam can be a suitable therapeutic option in this special population., (© 2022. The Author(s).)

Introduction: Migraine is a common comorbidity in patients with epilepsy. Considering the proven associations and the common pathophysiological features linking epilepsy and migraine, some anti-seizure medications (ASMs) have been considered as a treatment for both disorders. This study aimed at assessing both the effectiveness of perampanel (PER) on epileptic seizures and migraine attacks in patients with epilepsy and comorbid migraine, as well as the reduction in the monthly mean rate usage of rescue migraine medications., Methods: This observational, multi-centre study included adult patients with epilepsy and comorbid migraine who started PER to better control epileptic seizures and who were followed up for 12 months., Results: Thirty-one patients were included (mean age 40.13 ± 13.13 years; 67.0% female). At the 12-month follow-up visit, 27 patients were continuing PER concomitantly with 1 (45.2%) or 2 ASMs (54.8%). A significant reduction in epileptic seizures, migraine attacks, and the monthly use of rescue migraine medications between baseline and both 6- and 12-month follow-up visits was documented., Conclusion: PER demonstrated good effectiveness in reducing both epileptic seizures and migraine attacks in patients with comorbid epilepsy and migraine. Future studies with possibly larger samples are needed to evaluate the efficacy of PER in migraine other than epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s).)

Introduction: The main of the present study was to assess the effectiveness and tolerability of perampanel (PER) in association with 1 or 2 concomitant antiseizure medications (ASMs) in patients with epilepsy throughout a follow-up period of 24 months or longer in a real-world setting., Methods: This retrospective, observational, multi-center study collected data from both underage (<18 years old) and adult patients who had started PER in association with 1 or 2 ASMs. Only patients who had started PER and were followed up for at least 24 months were included. Response to treatment was analyzed at the 24-, 36-, and 48-month visits by considering the last visit undergone by patients. Subgroup analyses were performed according to age, gender, and epilepsy type and patients were categorized following PER treatment in concomitance with 1 or 2 ASMs to evaluate the factors affecting the achievement of seizure freedom (SF) at the 24-month FU., Results: Ninety-four patients were included (mean age 36.89 years; 51.1% female). At the 24-month follow-up visit, 90 (95.74%) patients were still receiving PER concomitantly with 1 or 2 ASMs. The mean PER dose was 6.02 mg/day and SF was achieved by 33 (35.1%) patients. A significantly higher SF rate was found in patients who had started PER with only 1 ASM when compared to those who had started PER with 2 concomitant ASMs. Effectiveness was maintained also in the subgroups of patients with a 36- or 48-month follow-up visit. Adult patients had a higher final daily dosage of PER than underage patients. Logistic regression found that the lowest number of previously failed ASMs was associated with a higher SF rate (p = 0.036)., Conclusion: Perampanel demonstrated a good effectiveness in association with 1 or 2 ASMs in both pediatric and adult patients, without having to use a high dose of the drug. The possibility to present SF was higher when PER was added early. Finally, the maintenance of effectiveness was observed also in the subgroups of patients with a follow-up of 36 and 48 months., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Clinical data regarding use of newer antiseizure medications (ASMs) in an older population are limited. In randomized-controlled, placebo-controlled trials, older patients are under-represented, and protocols deviate markedly from routine clinical practice, limiting the external validity of results. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Perampanel is a third-generation ASM and the first and only non-competitive alfa-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist., Objective: The aim of this study was to assess the effectiveness and tolerability of adjunctive perampanel over a 1-year period in a population of older patients with epilepsy treated in a real-world setting., Methods: Older (≥ 65 years of age) patients prescribed add-on perampanel at 12 Italian epilepsy centers were retrospectively identified. Seizure occurrence, adverse events (AEs), and drug withdrawal were analyzed. Effectiveness outcomes included the rates of seizure response (≥ 50% reduction in baseline monthly seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes were the rate of treatment discontinuation due to AEs and the incidence of AEs., Results: A total of 92 patients with a median age of 69 (range 65-88) years were included. The median daily dose of perampanel at 12 months was 6 mg (interquartile range 4-6 mg). At 12 months, 53 (57.6%) patients were seizure responders, and 22 (23.9%) patients were seizure free. Twenty (21.7%) patients discontinued perampanel; the reasons for treatment withdrawal were insufficient efficacy (n = 6/20; 30.0%), AEs (n = 12/20; 60.0%), and a combination of both (n = 2/20; 10%). The most common AEs included irritability (8.7%), somnolence (4.3%), and dizziness/vertigo (4.3%). The rate of behavioral and psychiatric AEs was higher in patients with history of psychiatric comorbidities (p = 0.044). There were no differences in the occurrence of behavioral and psychiatric AEs according to the concomitant use of levetiracetam (p = 0.776) and history of cognitive decline (p = 0.332)., Conclusions: Adjunctive perampanel was associated with improvement in seizure control and good tolerability in a real-life setting and can represent a viable therapeutic option in older patients with 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., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [ adj HR] = 1.07, 95% CI = 1.02-1.13, P = .009) and baseline monthly seizure frequency ( adj HR = 1.004, 95% CI = 1.001-1.008, P = .028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs., (© 2020 International League Against Epilepsy.)

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.

Purpose: To describe the concept, features and mechanisms of epileptic headache (EH)., Methods: Analysis of all published articles concerning EH and related subjects., Results: There are more than 30 published case studies of patients with headache as the only manifestation of a seizure, a condition that has been variously called "EH", "ictal epileptic headache", "hemicrania epileptica", "cephalic pain seizure". It is necessary to differentiate EH from "migralepsy" and "ictal non-epileptic headache". EH may be an isolated event or the initial phase of a seizure followed by other manifestations. An isolated EH is clinically relevant because it is often symptomatic of structural brain disease; this underlines the importance of a differential diagnosis as the head pain of EH has no specific diagnostic characteristics. The described cases indicate that the location of the foci may vary, thus suggesting the involvement of different parts of the pain network. EH is a "focal aware" seizure, but there are a few reports of cases in which it was associated with generalised epileptiform activity. A correct diagnosis of EH requires an ictal EEG recording showing epilepsy-compatible discharges that coincide with the onset and cessation of the headache. A rapid response to the acute administration of an antiepileptic drug may support the diagnosis., Conclusions: EH is a particular type of pain seizure that has a complex pathophysiology and, when isolated, requires differential diagnostic consideration. We believe that, although it is not frequent, pain as an ictal symptom should be highlighted in the operational classification of seizure types., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The interrelations between headache/migraine and epileptic seizures are an interesting topic, still lacking a systematization, which is the objective of the present revision. We organize the general setting on: (a) a distinction between pre-ictal, ictal, post-ictal and inter-ictal headaches, assuming "ictal" as epileptic seizure, and (b) the kind of headache, if it is of migraine type or not. Concerning pre-ictal migraine/headache, the necessity of its differentiation from an epileptic headache presenting as an aura of a seizure is stressed; this is connected with the indefiniteness of the term "migralepsy". The term "migraine aura-triggered seizure" should be used only in front of a proven triggering effect of migraine. Epileptic headache (called also "ictal epileptic headache") is a well-characterized entity, in which different types of head pain may occur and an ictal EEG is necessary for the diagnosis. It may present as an isolated event ("isolated epileptic headache"), requiring a differential diagnosis from other kinds of headache, or it may be uninterruptedly followed by other epileptic manifestations being in this case easily identifiable as an epileptic aura. Hemicrania epileptica is a very rare variant of epileptic headache, characterized by the ipsilaterality of head pain and EEG paroxysms. Ictal non-epileptic headache needs to be differentiated from epileptic headache. Post-ictal headaches are a frequent association of headache with seizures, particularly in patients suffering also from inter-ictal headache-migraine. The reported systematization of the topic led us to suggest a classification which is shown in Appendix.

A 67-year-old man complained of a transient blurring of vision in his right visual field lasting 30 min followed by headache. Two weeks later, the visual disturbance changed its pattern; it was described as the occurrence of brown round-shaped images in the right visual field spinning and turning for few seconds. This evolution from visual aura to visual seizures, with video-EEG correlation, supports the hypothesis of modification in threshold of cortical hyperexcitability from migraine to epilepsy.

Headache may be associated with seizures as a preictal, ictal, or postictal phenomenon, but it is often neglected because of the dramatic neurological manifestations of the seizure. Headache can also be the sole or predominant clinical manifestation of epileptic seizures, although this is a relatively rare condition. We describe two cases of focal symptomatic drug-resistant epilepsy with headache as the first ictal symptom. In both cases, the headache, which lasted a few seconds, was contralateral to the ictal discharge and did not have the clinical features of migraine. Ictal headache is a rare epilepsy symptom that can help to localize ictal EEG discharges. Recently, the term ictal epileptic headache has been proposed in cases in which headache is the sole ictal epileptic manifestation Diagnosis requires the simultaneous onset of headache with EEG-demonstrated ictal discharges., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The heart rate adjustment of ST depression (ST/HR Slope) has been shown by some authors to markedly improve the accuracy of treadmill exercise electrocardiogram for identifying and quantifying coronary artery disease. However, other authors have obtained different results. In the present study the results of our exercise electrocardiography laboratory are compared with the data obtained from the literature., Methods: Fifty patients (46 males and 4 females, age range 60 +/- 7 years) with suspect or certain coronary artery disease were referred for a routine treadmill exercise electrocardiogram, and subsequently underwent cardiac catheterization and selective coronary cineangiography to assess the severity of coronary obstruction. All patients exercised according to a recently reported modification of the standard Bruce protocol, proposed by Kligfield et al, for a more accurate evaluation of the ST/HR Slope, which was calculated in real time by a computerized system. Patients with coexisting valvular heart disease, cardiomyopathy, left bundle-branch block on the resting ECG, myocardial infarction within 8 weeks, diabetes mellitus, hypertensive response during exercise testing (diastolic blood pressure > 95 mm Hg and/or systolic blood pressure > 190 mm Hg), abnormalities or variations of the coronary arteries, were excluded from this study., Results: This method correctly identified 13 of 14 patients with multivessel coronary artery disease and 35 of 36 with less severe disease: one patient was false negative and another one false positive. Thus, in our exercise electrocardiography laboratory this approach shows a sensitivity of 93%, a specificity of 97%, a positive predictive value of 93% and a negative predictive value of 97% for the detection of severe coronary disease., Conclusions: These findings suggest that, in patients selected as in this study, the ST/HR slope is a good method which improves the clinical usefulness of the treadmill exercise electrocardiogram in coronary artery disease.

The clinical significance of corrected sinus node recovery time (CSNRT) and the natural and unnatural history of sinus node dysfunctions are not completely known. To gain some insight into this problem, 101 patients (pts) (54M, 47F, mean age +/- SD = 62.02 yrs +/- 14.42) with clinical and ECG signs of definite or suspected sick sinus syndrome (SSS) underwent an electrophysiologic study and then were prospectively followed for a mean period of 44.36 months +/- 18.96 (range: 2-78 months). The pts were divided into two groups: 1) Group A: 68 pts with prolonged CSNRT (greater than 500 msec); 2) Group B: 33 pts with normal CSNRT. Thirty-three pts of Group A (48.5%) and 2 pts of Group B (6.1%) received VVI pacemaker implantation (PM) immediately after the electrophysiologic study. The following results were obtained: 1) Pts of Group A showed a higher prevalence of organic heart disease and of ECG signs of definite SSS than pts of Group B. (p less than 0.05). Moreover, the higher the CSNRT in Group A pts, the more severe the ECG abnormalities of SSS. 2) Pts without PM, both of Group A and Group B, noted during the follow-up period a disappearance of neurological symptoms (syncopes and/or dizziness) and of ECG abnormalities of SSS in more than 50% of the cases. However, this was less evident in Group A pts compared with Group B pts (53.8% vs 78.6% regarding neurological symptoms and 54.3% vs 74.1% regarding ECG abnormalities of SSS) as well as in pts with organic heart disease in comparison with those with primitive SSS. Moreover, the number of pts who needed PM implantation during the follow-up period due to the worsening of clinical and ECG signs of SSS were higher in Group A than in Group B (20% vs 6.5%). The occurrence of cardiac death among the pts without PM was similar in pts of Group A (8.5%) and in those of Group B (9.7%). One pt of Group A without PM died suddenly (less than 1 hour). 3) Pts who required PM implantation were older (p less than 0.01) and showed a prevalence of organic heart disease higher (p less than 0.05) than those who did not require PM implantation. Pts with PM, both of Group A and Group B, showed a complete disappearance of syncopes and a clear-cut reduction of dizziness after implantation of it. On the contrary, dyspnea nearly always persisted and sometimes appeared when initially absent. Sudden and non-sudden cardiac death in PM pts (13.6%) was somewhat more frequent than in those without PM. 4) The incidence of stable atrial fibrillation was 12.1% in pts without PM and 27.2% in pts with PM. The occurrence of stable atrial fibrillation in pts without PM was generally not followed by clinical improvement. 5) The incidence of cerebrovascular accidents was approximately 8%. The accidents always occurred in pts with organic heart disease and often in the older pts (mean age: 75.1 yrs +/- 5.7) particularly in those with PM. A bradycardia-tachycardia syndrome was observed only in 3 pts who had a stroke...

Various electrocardiographic and vectorcardiographic (ECG-VCG) patterns of ventricular conduction disturbances are inducible by premature right atrial stimulation (PRAS). These patterns are a consequence of different degrees of refractoriness in the specialized ventricular conduction system. We observed that the intermediate phase of left bundle branch block (LBBB) induced by PRAS in 20 subjects with normal basal QRS (complexes) were similar to those of left ventricular hypertrophy (LVH). In 18 patients with basal ECG-VCG signs of LVH, right bundle branch block (RBBB) induced by PRAS produced a progressive disappearance of these signs and the "normalization" of the tracings. The initial maximum QRS vector decreased, disappeared or remained absent in the patients with LBBB induced by PRAS, and appeared (when absent in the basal VCG) and remained unchanged (when present) in patients with RBBB induced by PRAS. In this paper we discuss the electrogenetic implications of these data. The ECG-VCG sings of LVH are probably dependent on a slowed conduction in the left bundle branch system, while anatomical hypertrophy per se probably plays a less important role.

The typical QRS patterns of myocardial infarction (MI-QRS) are commonly attributed to myocardial cellular death. However, observation of a transient appearance of MI-QRS during coronary insufficiency, the disappearance of MI-QRS after coronary by-pass surgery and the appearance of MI-QRS after intracranial hemorrhage suggest that a different electrophysiological mechanism may be at work. There is a single convincing explanation for all these observations. It seems possible, at least theoretically, that a localized conduction disturbance can generate or contribute to the generation of the MI-QRS. The results obtained in nine out of 194 cases studied by means of premature right atrial stimulation (PRAS) in our laboratory seem to confirm this hypothesis. In five of them we observed typical MI-QRS in the aberrant beats which were absent in the basal tracings. In the other four cases, MI-QRS which were present in basal tracings disappeared in the aberrant beats. In three of these a reduction in the duration of QRS was also observed, while in the fourth the duration of QRS did not change. In no case could the alterations of QRS (induction or disappearance of MI-QRS) be explained by a classical conduction disturbance, preexcitation or by a premature ventricular beat. While the induction of MI-QRS was clearly due to an aberrant conduction in the supraventricular beats, the disappearance of basal MI-QRS changes in premature supraventricular beats is more difficult to explain. One possible electrophysiological mechanism could be a supernormal phase conduction. If this is the case, the basal MI-QRS could be due to a ventricular conduction disturbance. In conclusion, our results suggest that MI-QRS can be generated, at least in our cases, by a localized conduction disturbance.

Three cases of accelerated idioventricular rhythm with isorhythmic A-V dissociation are presented. One case was affected by hypertrophic non obstructive myocardiopathy and two cases were affected by coronary heart disease with previous myocardial infarction. In all the cases of the arrhythmia persisted for days or months. By means of the electrophysiological study we could establish that 1) the focus was not protected by entrance block and 2) it was localized in the main branches of the conduction system. In the first case the focus was localized in the right bundle branch, in the second case, it was localized in the anterior fascicle of the left bundle branch and in the third case in the posterior fascicle of the left bundle branch. These electrophysiological characteristics suggest that the arrhythmia was due to increased firing of normal idioventricular pacemakers. On the basis of this electrogenetic interpretation we outline that in our cases the term of accelerated idioventricular rhythm should be preferred to others used in literature such as slow ventricular tachycardia.