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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, ß, 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.
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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.
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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.
Subject(s)
Epilepsies, Partial , Epilepsy , Nitriles , Pyridones , Male , Adult , Humans , Female , Anticonvulsants/adverse effects , Epilepsies, Partial/drug therapy , Retrospective Studies , Levetiracetam/therapeutic use , Lacosamide/therapeutic use , Epilepsy/drug therapy , Pyrrolidinones/therapeutic use , Treatment OutcomeABSTRACT
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.
Subject(s)
Drug Resistant Epilepsy , Epilepsies, Partial , Epilepsy , Suicide , Adult , Humans , Suicidal Ideation , Depression/etiology , Suicide/psychology , Seizures/complications , Epilepsy/complications , Drug Resistant Epilepsy/drug therapy , Drug Resistant Epilepsy/complications , Epilepsies, Partial/drug therapy , Epilepsies, Partial/complicationsABSTRACT
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.
Subject(s)
Anticonvulsants , Epilepsies, Partial , Adult , Humans , Anticonvulsants/therapeutic use , Retrospective Studies , Treatment Outcome , Drug Therapy, Combination , Seizures/drug therapy , Seizures/chemically induced , Epilepsies, Partial/drug therapy , Pyrrolidinones/therapeutic useABSTRACT
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.
Subject(s)
Classical Lissencephalies and Subcortical Band Heterotopias , Epilepsy , Humans , Female , Child , Male , Cross-Sectional Studies , Microtubule-Associated Proteins , Glasgow Outcome Scale , Magnetic Resonance ImagingABSTRACT
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.
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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.
Subject(s)
Anticonvulsants , Epilepsies, Partial , Adult , Anticonvulsants/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Epilepsies, Partial/drug therapy , Freedom , Humans , Middle Aged , Pyrrolidinones/therapeutic use , Seizures/drug therapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Anticonvulsants , Epilepsy , Aged , Anticonvulsants/adverse effects , Double-Blind Method , Drug Therapy, Combination , Epilepsy/drug therapy , Humans , Italy , Pyrrolidinones , Retrospective Studies , Seizures/drug therapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Epilepsy , Stroke , Adult , Aged , Anticonvulsants/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Epilepsy/chemically induced , Epilepsy/etiology , Humans , Italy , Middle Aged , Pyrrolidinones/therapeutic use , Retrospective Studies , Seizures/drug therapy , Stroke/complications , Stroke/drug therapy , Treatment OutcomeABSTRACT
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 12â¯months. RESULTS: Thirty-one patients were included (mean age 40.13⯱â¯13.13â¯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.
Subject(s)
Epilepsy , Migraine Disorders , Adult , Anticonvulsants/therapeutic use , Comorbidity , Epilepsy/complications , Epilepsy/drug therapy , Epilepsy/epidemiology , Female , Humans , Male , Middle Aged , Migraine Disorders/complications , Migraine Disorders/drug therapy , Migraine Disorders/epidemiology , Nitriles , Pyridones/therapeutic useABSTRACT
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.
Subject(s)
Anticonvulsants/therapeutic use , Drug Resistant Epilepsy/drug therapy , Epilepsies, Partial/drug therapy , Pyrrolidinones/therapeutic use , Adult , Anticonvulsants/administration & dosage , Chemotherapy, Adjuvant , Female , Humans , Italy , Levetiracetam/administration & dosage , Levetiracetam/therapeutic use , Male , Middle Aged , Pyrrolidinones/administration & dosage , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Anticonvulsants/therapeutic use , Epilepsy , Nitriles/therapeutic use , Pyridones/therapeutic use , Aged , Aged, 80 and over , Anticonvulsants/adverse effects , Epilepsy/drug therapy , Humans , Retrospective Studies , Treatment OutcomeABSTRACT
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 24â¯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 (pâ¯=â¯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.
Subject(s)
Anticonvulsants , Epilepsy , Adolescent , Adult , Anticonvulsants/therapeutic use , Child , Epilepsy/drug therapy , Female , Follow-Up Studies , Humans , Male , Nitriles , Pyridones/therapeutic use , Retrospective Studies , Treatment OutcomeABSTRACT
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 6â¯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 100â¯mg (range 50-300â¯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 6â¯h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39-202; pâ¯=â¯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.
Subject(s)
Status Epilepticus , Anticonvulsants/therapeutic use , Female , Humans , Italy , Male , Middle Aged , Pyrrolidinones/adverse effects , Retrospective Studies , Status Epilepticus/drug therapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Pyrrolidinones/therapeutic use , Adult , Drug Therapy, Combination , Female , Humans , Levetiracetam/therapeutic use , Male , Middle Aged , Proportional Hazards Models , Treatment OutcomeABSTRACT
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.
Subject(s)
Brain Neoplasms/complications , Epilepsy/etiology , Epilepsy/therapy , HumansABSTRACT
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.
Subject(s)
Epilepsy/complications , Headache/etiology , Databases, Bibliographic , Headache/diagnosis , HumansABSTRACT
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.