scholarly journals Retention Rate and Efficacy of Perampanel with a Slow Titration Schedule in Adults

2020 ◽  
pp. 1-7
Author(s):  
Mazen Basheikh ◽  
R. Mark Sadler
Keyword(s):  
Seizure Frequency ◽  
Retention Rate ◽  
Responder Rate ◽  
Dose Titration ◽  
Seizure Freedom ◽  
Chart Audit ◽  
Generalized Seizures ◽  
Included Patient ◽  
Generalized Epilepsy

ABSTRACT: Rationale: The manufacturer of perampanel (PER) suggests an initial adult dose of 2–4 mg/day and an upward dose titration of 2 mg at no more frequently than 1- or 2-week intervals when used with enzyme-enhancing antiepileptic drugs (AEDs) or nonenzyme-enhancing AEDs, respectively. The general practice in our clinic is an initial dose of PER 2 mg/day and titrated by 2 mg/4 weeks to an initial target of 6 mg/day. Methods: Retrospective chart audit of patients starting PER in an adult epilepsy clinic between September 2013 and November 2016 with at least one 6-month follow-up visit was reviewed. Data collection included patient demographics, seizure characteristics, past and concurrent therapy, monthly seizure frequency before PER and at 6-month visit, and characteristics of PER discontinuation. Efficacy of treatment was assessed with the Engel classification and 50% responder rate. Results: N = 102 patients; mean age = 40 years and 54% females. Focal onset seizures 85%, generalized 13%, and unknown 2%. Median prior AED exposure = 6 (range 3–20); median concomitant AED use = 2 (range 1–5). Follow-up range was 6–37 months. The median seizure frequency/month prePER treatment was 6 (range 0–30) for focal onset seizures and 1 (range 0–6) for generalized seizures. The retention rate amongst all patients at 6 months was 78.4%. At 6-month follow-up, 36% of all patients achieved Engel class I (seizure freedom) (30.7% of patients with focal onset seizures and 63.6% with generalized epilepsy). The 50% responder rate was 52% and 82% for focal and generalized epilepsy, respectively. Conclusion: PER has a good retention rate when titrated slowly and thus encouraging seizure freedom results in an otherwise medically refractory epilepsy population.

Efficacy and Tolerability of Rufinamide in Epileptic Children Younger Than 4 Years

2020 ◽  
pp. 088307382096715
Author(s):  
Ahmet Tanritanir ◽  
Xiaofan Wang ◽  
Tobias Loddenkemper
Keyword(s):  
Adverse Events ◽  
Seizure Frequency ◽  
Retention Rate ◽  
Complete Information ◽  
Interquartile Range ◽  
Pediatric Epilepsy ◽  
Seizure Freedom ◽  
Seizure Reduction ◽  
Epileptic Children

Background: Rufinamide, a triazole derivative, is a new-generation antiseizure medication with a novel mechanism of action. We evaluated the efficacy and safety of rufinamide treatment in children with epilepsy younger than 4 years at our center. Methods: In this retrospective study, we included children younger than 4 years who had pharmacologically resistant epilepsy and were treated with rufinamide at Boston Children’s Hospital between June 2010 and June 2018. Safety and efficacy of rufinamide treatment were assessed immediately prior to initiation of rufinamide and at the last follow-up visit. Responders were defined as patients who had greater than 50% reduction in seizure frequency on follow-up as compared to baseline. Results: We reviewed records of 128 children and included 103 with complete information. Patients consisted of 60 boys (58%), with a median age of 20 months (interquartile range 13-28, range 2-36). Median treatment duration was 15 months, and median rufinamide dosage at the last follow-up was 42 mg/kg/d (interquartile range 34-56). At the last follow-up, seizure frequency decreased (450 vs 90, P<.001) and overall seizure reduction was 54%. Fifty-one patients (49.5%) were responders with 94% seizure reduction, including 20 (19.4%) who achieved seizure freedom. Treatment retention rate at 12 months was 63%. Thirty patients (29%) developed adverse events and 41 patients (39.8%) discontinued rufinamide because of adverse events (15; 14.5%) and lack of efficacy (26; 25%). Conclusion: Rufinamide is effective in reducing seizure frequency in pediatric epilepsy patients younger than 4 years, and overall well tolerated.

scholarly journals Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Neurology ◽  
2020 ◽  
Vol 95 (9) ◽  
pp. e1244-e1256 ◽  
Author(s):  
Dileep R. Nair ◽  
Kenneth D. Laxer ◽  
Peter B. Weber ◽  
Anthony M. Murro ◽  
Yong D. Park ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Seizure Frequency ◽  
Focal Epilepsy ◽  
Responder Rate ◽  
Seizure Freedom ◽  
Open Label ◽  
Cognitive Domains ◽  
Signed Rank

ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04–9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2).ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.ClinicalTrials.gov identifierNCT00572195.Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Potassium Bromide in the Treatment of Pediatric Refractory Epilepsy

2019 ◽  
Vol 34 (10) ◽  
pp. 582-585 ◽  
Author(s):  
Kazuo Kodama ◽  
Taku Omata ◽  
Yoshimi Watanabe ◽  
Hiromi Aoyama ◽  
Yuzo Tanabe
Keyword(s):  
Adverse Effects ◽  
Seizure Frequency ◽  
Refractory Epilepsy ◽  
Focal Epilepsy ◽  
Dravet Syndrome ◽  
Generalized Seizures ◽  
Clonic Seizures ◽  
Moderate Effect ◽  
Generalized Epilepsy ◽  
Free Status

Objective: We evaluated potassium bromide’s (KBr’s) efficacy and tolerability for pediatric refractory epilepsy. Methods: We retrospectively reviewed the records of 42 patients treated with KBr in our hospital between 2008 and 2016 (age: 4 months to 19 years; mean: 6.2 years). Thirteen of them had 2 seizure types. The treatment durations ranged from 1 month to 6 years (mean: 15.0 months). Results: KBr had an excellent effect (seizure-free status) in 3 patients (7.1%), a moderate effect (>50% reduction in seizure frequency from the pretreatment baseline) in 21 patients (50.0%), and no effect (<50% reduction in seizure frequency from the pretreatment baseline) in 18 patients (42.9%). The effective daily doses ranged from 20 to 80 mg/kg (mean: 50.0 mg/kg). KBr was effective in 59.1% patients with generalized epilepsy (n = 22), 55.6% patients with focal epilepsy (n = 18), and both patients with Dravet syndrome. An excellent or moderate effect was found in 72.2% patients with tonic seizures (n = 18), 66.6% patients with generalized tonic-clonic seizures (n = 6), 75.0% patients with secondary generalized seizures (n = 4), 46.2% patients with focal seizures (n = 13), and 20% patients with infantile spasms (n = 10) but no patients with myoclonic seizures (n = 2). Adverse effects including drowsiness, excitement, and rashes were reported in 13 patients (31.0%). Conclusions: These findings suggest that KBr is particularly effective for tonic seizures, generalized tonic-clonic seizures, and secondary generalized seizures. Although the adverse effects need further attention, KBr should be considered for pediatric refractory epilepsy.

Variations in Seizure Frequency During Pregnancy and Postpartum by Epilepsy Type

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013056
Author(s):  
P. Emanuela Voinescu ◽  
Alexa N Ehlert ◽  
Camden P Bay ◽  
Stephanie Allien ◽  
Page B Pennell
Keyword(s):  
Frontal Lobe ◽  
Seizure Frequency ◽  
Postpartum Period ◽  
Focal Epilepsy ◽  
Post Partum ◽  
Frontal Lobe Epilepsy ◽  
Seizure Freedom ◽  
Pregnancy And Postpartum ◽  
Individual Participant ◽  
Generalized Epilepsy

Objective:To assess whether increased seizure frequency during pregnancy and post-partum is influenced by epilepsy type, seizure location, and antiseizure medications.Methods:Clinical data was collected in a longitudinal prospective database of pregnant women with epilepsy at Brigham and Women’s Hospital. Within each individual participant, baseline seizure frequency was calculated for the 9 months preconception, and it was determined if seizure frequency increased during pregnancy or the postpartum period. Seizure frequency was calculated for each 4-week interval during pregnancy. Generalized estimating equations for logistic regression were applied.Results:Ninety-nine patients contributing 114 pregnancies were included from 2013-2018. Increased seizure frequency occurred more often during pregnancies of women with focal versus generalized epilepsy (21.1% vs 5.3%, OR 4.70; 95% CI (1.00, 22.00); p = 0.0497). Among women with focal epilepsy, increased seizure frequency occurred more often in those with frontal lobe epilepsy (OR 8.00; 95 % CI (2.19, 29.21); p = 0.0017). There was no difference in seizure worsening in the postpartum period between focal and generalized (11.1% vs 9.1%, p=0.4478), or frontal and other focal (18.8% vs 6.0%; p=0.1478) epilepsy groups. Pregnancies on polytherapy had higher odds of seizure worsening compared to monotherapy (OR = 8.36, 95% CI = (2.07, 33.84), p = 0.0029), regardless of the medication or epilepsy type. A lack of preconception seizure freedom was also associated with increased seizure frequency during pregnancy (OR = 6.418; p = 0.0076).Conclusion:Women with focal epilepsy have higher likelihood of seizure worsening during pregnancy compared to women with generalized epilepsy; frontal lobe epilepsy poses an especially elevated risk. Polytherapy and lack of preconception seizure freedom are additional predictors for an increased likelihood of seizure worsening.

scholarly journals Seizure control after radiosurgery for cerebral arteriovenous malformations: a 25-year experience

2019 ◽  
Vol 131 (6) ◽  
pp. 1763-1772
Author(s):  
Ajay Niranjan ◽  
Ahmed Kashkoush ◽  
Hideyuki Kano ◽  
Edward A. Monaco ◽  
John C. Flickinger ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Arteriovenous Malformations ◽  
Seizure Control ◽  
Venous Drainage ◽  
Seizure Outcome ◽  
Seizure Freedom ◽  
Impaired Awareness ◽  
Free Status

OBJECTIVESeizures are the second-most common presenting symptom in patients with lobar arteriovenous malformations (AVMs). However, few studies have assessed the long-term effect of stereotactic radiosurgery (SRS) on seizure control. The authors of this study assess the outcome of SRS for these patients to identify prognostic factors associated with seizure control.METHODSPatients with AVM who presented with a history of seizure and underwent SRS at the authors’ institution between 1987 and 2012 were retrospectively assessed. The total cohort included 155 patients with a mean follow-up of 86 months (range 6–295 months). Primary outcomes assessed were seizure frequency, antiepileptic drug regimen, and seizure freedom for 6 months prior to last follow-up.RESULTSSeizure-free status was achieved in 108 patients (70%), with an additional 23 patients (15%) reporting improved seizure frequency as compared to their pre-SRS status. The median time to seizure-free status was estimated to be 12 months (95% CI 0–27 months) as evaluated via Kaplan-Meier survival analysis. The mean seizure frequency prior to SRS was 14.2 (95% CI 5.4–23.1) episodes per year. Although not all patients tried, the proportion of patients successfully weaned off all antiepileptic drugs was 18% (28/155 patients). On multivariate logistic regression, focal impaired awareness seizure type (also known as complex partial seizures) and superficial venous drainage were significantly associated with a decreased odds ratio for seizure-free status at last follow-up (OR 0.37 [95% CI 0.15–0.92] for focal impaired awareness seizures; OR 0.36 [95% CI 0.16–0.81] for superficial venous drainage). The effects of superficial venous drainage on seizure outcome were nonsignificant when excluding patients with < 2 years of follow-up. AVM obliteration did not correlate with long-term seizure freedom (p = 0.202, chi-square test).CONCLUSIONSThis study suggests that SRS improves long-term seizure control and increases the likelihood of being medication free, independently of AVM obliteration. Patients with focal impaired awareness seizures were less likely to obtain long-term seizure relief.

Adult phenotype of KCNQ2 encephalopathy

2021 ◽  
pp. jmedgenet-2020-107449
Author(s):  
Stephanie Boets ◽  
Katrine M Johannesen ◽  
Anne Destree ◽  
Filippo Manti ◽  
Georgia Ramantani ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Sleep Problems ◽  
Epileptic Encephalopathy ◽  
Seizure Type ◽  
Seizure Freedom ◽  
Childhood And Adolescence ◽  
Seizure Recurrence ◽  
Impaired Awareness ◽  
Limb Spasticity

BackgroundPathogenic KCNQ2 variants are a frequent cause of developmental and epileptic encephalopathy.MethodsWe recruited 13 adults (between 18 years and 45 years of age) with KCNQ2 encephalopathy and reviewed their clinical, EEG, neuroimaging and treatment history.ResultsWhile most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood. The most common seizure type was tonic seizures (early) infancy, and tonic-clonic and focal impaired awareness seizures later in life. Ten individuals (77%) were seizure-free at last follow-up. In 38% of the individuals, earlier periods of seizure freedom lasting a minimum of 2 years followed by seizure recurrence had occurred. Of the 10 seizure-free patients, 4 were receiving a single antiseizure medication (ASM, carbamazepine, lamotrigine or levetiracetam), and 2 had stopped taking ASM. Intellectual disability (ID) ranged from mild to profound, with the majority (54%) of individuals in the severe category. At last contact, six individuals (46%) remained unable to walk independently, six (46%) had limb spasticity and four (31%) tetraparesis/tetraplegia. Six (46%) remained non-verbal, 10 (77%) had autistic features/autism, 4 (31%) exhibited aggressive behaviour and 4 (31%) destructive behaviour with self-injury. Four patients had visual problems, thought to be related to prematurity in one. Sleep problems were seen in six (46%) individuals.ConclusionSeizure frequency declines over the years and most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are common during childhood and adolescence. Most adult patients have severe ID. Motor, language and behavioural problems are an issue of continuous concern.

Experience with Eslicarbazepine Acetate Treatment at a Pediatric Epilepsy Center

2020 ◽  
Author(s):  
Ahmet Tanritanir ◽  
Xiaofan Wang ◽  
Tobias Loddenkemper
Keyword(s):  
Sleep Problems ◽  
Retention Rate ◽  
Intractable Epilepsy ◽  
Pediatric Epilepsy ◽  
Seizure Freedom ◽  
Eslicarbazepine Acetate ◽  
Once Daily ◽  
Epilepsy Center ◽  
One Year

AbstractEslicarbazepine acetate (ESL) is a novel, once-daily antiseizure medication. We evaluated the efficacy and safety profile of ESL treatment in epilepsy patients at a single tertiary epilepsy center. In this retrospective observational study, we included 32 patients with pharmacologically intractable epilepsy receiving ESL at Boston Children's Hospital from June 2014 to June 2018. We assessed treatment outcome in terms of efficacy and tolerability at first and last follow-up (f/u). Median age was 17 (interquartile range: 10.8–20.7; range: 6.5–36) years. Twelve (37.5%) patients, including three with seizure freedom, were responders at last f/u. Eleven patients discontinued ESL due to seizure worsening (9, 28%), adverse events (AEs) (2, 6%) or both (4, 12%). Responders showed greater seizure reduction at last f/u with fewer AEs as compared with nonresponders. Ten (31%) patients developed AEs, the most common being sleep problems (5, 15%). One-year retention rate with ESL treatment was 54%. In conclusion, ESL had a good response rate in patients with pharmacologically intractable epilepsy, with about one-third of patients developing AEs.

scholarly journals First clinical postmarketing experiences in the treatment of epilepsies with brivaracetam: a retrospective observational multicentre study

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e030746 ◽  
Author(s):  
Katja Menzler ◽  
Peter Michael Mross ◽  
Felix Rosenow ◽  
Susanne Schubert-Bast ◽  
Laurent Maximilian Willems ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Multicentre Study ◽  
Seizure Frequency ◽  
Real Life ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Seizure Freedom ◽  
Clinical Settings ◽  
Synaptic Vesicle Protein 2A

ObjectivesBrivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting.DesignRetrospective, observational multicentre study.SettingWe retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist.ParticipantsData of 615 epilepsy patients treated with BRV were included in the study.Primary and secondary outcome measuresEfficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed.ResultsOverall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV.ConclusionsThe present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

scholarly journals Effective and safe diet therapies for Lennox-Gastaut syndrome with mitochondrial dysfunction

2020 ◽  
Vol 13 ◽  
pp. 175628641989781
Author(s):  
Ji-Hoon Na ◽  
Heung-Dong Kim ◽  
Young-Mock Lee
Keyword(s):  
Cognitive Function ◽  
Mitochondrial Dysfunction ◽  
Retention Rate ◽  
Tertiary Care ◽  
Reduction Rate ◽  
Cognitive Status ◽  
Seizure Freedom ◽  
Seizure Reduction ◽  
Gastrointestinal Problems

Background: Lennox-Gastaut syndrome (LGS) is a typical intractable form of epilepsy that most often occurs between the second and sixth year of life. This study aimed to evaluate the clinical efficacy and safety of ketogenic diet therapies (DTs) for LGS with mitochondrial dysfunction. Methods: This was a retrospective study involving 20 LGS patients with mitochondrial dysfunction who received several DTs from 2004 to 2014 at a single tertiary care center. Seizure reduction rate, cognitive function, retention rate, electroencephalography (EEG) changes, and adverse effects were examined before and after DTs. Results: The retention rates at 1 and 2 years after initiation of DTs were 45% and 40%, respectively. After 1-year follow up, we observed seizure freedom in two patients, 75% seizure reduction in two patients, 50% reduction in three patients, and 25% reduction in one patient. After 2-year follow up, the outcomes were seizure freedom in two patients, 90% seizure reduction in one patient, 75% reduction in two patients, and 50% reduction in two patients. EEG findings improved in nine patients. Nine patients were treated with DTs for 1 year; all patients demonstrated improved cognitive status. Eight patients were treated with DTs for 2 years, of whom seven had improved cognitive status. Poor tolerability of DTs was due to poor oral intake and gastrointestinal problems. Conclusions: We demonstrate that, in LGS with mitochondrial dysfunction, improvement of seizures and cognitive function are not inferior to those in other patients treated with DTs. This study showed that DTs are efficacious and feasible for LGS patients with mitochondrial dysfunction and can significantly improve their prognosis.

THUR 058 Eslicarbazepine acetate as monotherapy in clinical practice

2018 ◽  
Vol 89 (10) ◽  
pp. A7.1-A7
Author(s):  
McMurray Rob ◽  
Delanty Norman ◽  
Villanueva Vicente
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Seizure Frequency ◽  
Adjunctive Therapy ◽  
Pooled Analysis ◽  
Responder Rate ◽  
Seizure Freedom ◽  
European Studies ◽  
Eslicarbazepine Acetate ◽  
Everyday Clinical Practice

PurposeTo assess eslicarbazepine acetate (ESL) as monotherapy in everyday clinical practice.MethodEuro-Esli was a pooled analysis of 14 European studies. In a subanalysis, data were compared for patients treated initially with ESL monotherapy versus adjunctive therapy, and for patients treated at last visit with ESL monotherapy versus adjunctive therapy.Assessments included responder rate (≥50% seizure frequency reduction), seizure freedom rate (seizure freedom at least since prior visit) and incidence of adverse events (AEs).ResultsESL was used as monotherapy in 88/2045 and 229/1340 patients initially and at last visit, respectively. At 12 months, responder and seizure freedom rates were significantly higher in patients treated initially with ESL monotherapy versus adjunctive therapy (responder: 94.1% versus 74.8%; seizure freedom: 88.2% versus 39.0%), and in patients treated at last visit with ESL monotherapy versus adjunctive therapy (responder: 93.2% versus 70.4%; seizure freedom: 77.4% versus 25.9%). Overall incidence of AEs was similar in patients treated initially with ESL monotherapy and adjunctive therapy (29.4% versus 34.4%), and in patients treated at last visit with ESL monotherapy and adjunctive therapy (27.1% versus 30.8%).ConclusionESL was significantly more effective when used as monotherapy compared with adjunctive therapy; safety/tolerability was generally comparable.Supported by Eisai

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