| 1. |
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| 2. |
- Andermann, E., et al.
(författare)
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Comparative analysis of the safety and tolerability of eslicarbazepine acetate in older (>= 60 years) and younger (18-59 years) adults
- 2021
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 169
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the safety and tolerability of eslicarbazepine acetate (ESL), a once-daily oral anti-seizure drug (ASD), in older and younger adult patient populations. Methods: Two post-hoc pooled data analyses were performed: one from three Phase III studies in patients with focal (partial-onset) seizures who were taking 1-3 concomitant ASDs; the other from five Phase II studies in patients from non-epilepsy populations not taking other ASDs chronically and/or at a clinically-effective anti-seizure dose. The frequencies of treatment-emergent adverse events (TEAEs) were calculated for the older (>= 60 years) and younger (18-59 years) adults separately. Results: In the focal seizures study pool, 4.1 % of patients (58/1431) were aged >= 60 years. The overall frequency of TEAEs was 77.5 % in older ESL-treated patients and 72.6 % in younger ESL-treated patients (p = 0.495). For patients who received placebo, the overall frequency of TEAEs was 50.0 % in the older adults and 57.5 % in the younger adults (p = 0.531). The overall placebo-adjusted frequency of TEAEs was 27.5 % in older adults and 15.1 % in younger adults. The placebo-adjusted frequencies of the TEAEs dizziness, somnolence, headache, nausea, diplopia, blurred vision, and ataxia were >= 5 % higher, and frequencies of vomiting and vertigo were >= 2 % higher in older than younger adults. The overall frequency of TEAEs leading to discontinuation was 15.0 % in older ESL-treated patients and 17.6 % in younger ESL-treated patients (p = 0.647); the frequency increased with increasing ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 5.6 % in older adults and 6.6 % in younger adults (p = 0.847). In the non-epilepsy study pool, 30.2 % of patients (515/1705) were aged >= 60 years. The overall frequency of TEAEs was 56.9 % in older ESL-treated patients and 58.8 % in younger ESL-treated patients. The placebo-adjusted frequencies were 14.9 % in older and 15.1 % in younger ESL-treated patients. The placebo-adjusted frequencies of the TEAEs nausea, vomiting, fatigue, and vertigo were >= 2 % higher in older adults, whereas somnolence was >= 2 % higher in younger adults. The overall frequency of TEAEs leading to discontinuation was 18.3 % in older ESL-treated patients and 12.1 % in younger ESL-treated patients (p = 0.003); frequencies were not related to ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 8.0 % in older adults and 5.6 % in younger adults (p = 0.407). Conclusion: Analyses of adverse event data support the safety and tolerability of ESL in adults aged >= 60 years. In the limited number of older patients with focal seizures taking ESL plus concomitant ASDs (n = 40), the frequency of TEAEs was generally higher than in younger adults. However, in the non-epilepsy patient group (in which the number of older patients was ten times larger; 427 patients taking ESL without concomitant ASDs), no marked age-related TEAE differences were observed, suggesting that increased ASD load associated with adjunctive therapy may complicate treatment selection in older patients, due to risk of increased adverse events. As is common practice for all ASDs, balancing clinical response and tolerability is needed in this vulnerable group of patients.
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| 3. |
- Andermann, E., et al.
(författare)
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Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures
- 2018
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 82, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. Methods: This was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400 mg (studies 301 and 302 only), 800 mg, or 1200 mg once daily (QD) for 14 weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. Results: The analysis population included 1447 patients (ESL, n = 1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p = 0.802). The incidence of depression and suicidality-related TEAEs was higher for ESL (7.4%) vs. placebo (3.8%) (p = 0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was higher for ESL (7.1%) vs. placebo (4.0%) (p = 0.023); incidences of memory impairment, attention disturbance, apathy, and aphasia were higher for ESL 1200 mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs were (0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to discontinuation occurred in 1.9% and 1.4% of patients taking ESL. and 0.7% and 0.5% taking placebo, respectively. Conclusions: In phase III clinical trials of adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were reported infrequently with ESL and placebo. The incidences of depression and suicidality-related TEAEs and of cognitive TEAEs were higher for patients taking ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading to discontinuation, were low with ESL and placebo. © 2017
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| 4. |
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| 5. |
- Bauer, J, et al.
(författare)
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Levetiracetam: a long-term follow-up study of efficacy and safety.
- 2006
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 114:3, s. 169-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the efficacy and safety of long-term add-on treatment with levetiracetam 1,000-4,000 mg/day. PATIENTS AND METHODS: In this multicenter, open-label follow-up study, 505 patients, from 10 European countries, who had benefited from previous add-on treatment with levetiracetam in a clinical trial or compassionate-use program were enrolled; 274 (54.3%) stayed to the end. Most then continued levetiracetam by prescription or in a named patient program, where it was not yet commercially available. Mean treatment duration was 1,045 days (range: 24 days to >7 years). Median daily dosage was 3,000 mg/day (range: 250-6,000 mg/day), with 250 (49.5%) patients receiving levetiracetam for >3 years. RESULTS: Median total and partial seizure frequency per week over the evaluation period were 0.8 and 0.7; seizure frequency per week was generally stable over time and remained low. There was a probability of 6.6% of remaining seizure-free for the first 3 years, and of 18.9% of having a seizure-free period of at least 3 years at any time. Most adverse events were mild or moderate and unrelated to study drug. Levetiracetam was well tolerated, and provided stable seizure control during long-term treatment.
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| 6. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy
- 2020
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Ingår i: Cns Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 34:6, s. 661-672
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Tidskriftsartikel (refereegranskat)abstract
- Background In recent randomized, placebo-controlled, phase III trials, highly purified cannabidiol demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome. It is anticipated that antiepileptic drugs such as stiripentol and valproate will be administered concomitantly with cannabidiol. Objectives This trial evaluated the effect of cannabidiol on steady-state pharmacokinetics of stiripentol or valproate in patients with epilepsy, and the safety and tolerability of cannabidiol. Methods This phase II, two-arm, parallel-group, double-blind, randomized, placebo-controlled trial recruited male and female patients with epilepsy aged 16-55 years. Patients receiving a stable dose of stiripentol or valproate were randomized 4:1 to receive concomitant double-blind cannabidiol or placebo. Patients received plant-derived, highly purified cannabidiol medicine (Epidiolex(R) in the USA; Epidyolex(R) in the EU; 100 mg/mL oral solution) at a dose of 20 mg/kg/day from day 12 to 26, following a 10-day dose-escalation period. Blood samples for pharmacokinetic evaluations were collected on days 1 and 26 before stiripentol/valproate dosing and up to 12 h postdose. Treatment-emergent adverse events (AEs) were recorded. Results In total, 35 patients were recruited to the stiripentol arm (n = 14) or the valproate arm (n = 21). Both the safety and the pharmacokinetic populations of the stiripentol arm comprised 14 patients (2 placebo; 12 cannabidiol). The safety population of the valproate arm comprised 20 patients (4 placebo; 16 cannabidiol; one withdrew before receiving treatment); the pharmacokinetic population comprised 15 patients (3 placebo; 12 cannabidiol). Concomitant cannabidiol led to a small increase in stiripentol exposure (17% increase in maximum observed plasma concentration [C-max]; 30% increase in area under the concentration-time curve over the dosing interval [AUC(tau)]). Concomitant cannabidiol also had little effect on valproate exposure (13% decrease in C-max; 17% decrease in AUC(tau)) or its metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA) (23% decrease in C-max; 30% decrease in AUC(tau)). All changes in exposure are expressed as the dose-normalized geometric mean (CV%) day 26 to day 1 ratio. The most common AE was diarrhea; most AEs were mild. Two patients discontinued cannabidiol because of serious AEs (rash [n = 1] in the stiripentol arm; hypertransaminasemia [n = 1] in the valproate arm). A separate in vitro study investigated the bidirectional effect of cannabidiol, or its metabolite 7-carboxy-cannabidiol, on valproate plasma protein binding; no change in plasma protein binding was observed for either compound. Conclusions The clinical relevance of the increase in stiripentol exposure is unknown; patients receiving cannabidiol and stiripentol concomitantly should be monitored for adverse reactions as individual patient responses may vary. Coadministration of cannabidiol did not affect the pharmacokinetics of valproate or its metabolite, 4-ene-VPA, in adult patients with epilepsy. Safety results were consistent with the known safety profile of cannabidiol at a dose of 20 mg/kg/day. Clinicaltrials.gov: NCT02607891.
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| 7. |
- Ben-Menachem, Elinor, 1945
(författare)
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AAN/AES guidelines on use of new AEDS.
- 2005
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 5:1, s. 30-2
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Ben-Menachem, Elinor, 1945
(författare)
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Data from regulatory studies: What do they tell? What don't they tell?
- 2005
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Ingår i: Acta neurologica Scandinavica. Supplementum. - : Hindawi Limited. - 0065-1427 .- 0001-6314 .- 1600-0404. ; 181, s. 21-5
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Tidskriftsartikel (refereegranskat)abstract
- Phase III studies of antiepileptic drugs (AEDs) are specifically designed to satisfy strict regulatory criteria. As they are conducted in protocol-restricted patient populations over short treatment periods and employ fixed study designs and dosing schedules, they are not fully representative of 'real-life' clinical practice. Therefore, in order to provide an overall assessment of clinical performance, regulatory studies must be backed up by post-marketing clinical experience. Phase IV studies provide information on a drug's performance in a setting more closely representing real clinical practice, with broader patient populations and a more flexible approach to individual treatment. Prospective long-term studies allow the determination of efficacy and safety (and cost-effectiveness) over extended treatment periods; these studies and audit data provide a means of assessing idiosyncratic side effects, unusual interactions and the effects of an AED in rare patient groups. By complementing regulatory evidence with real-life clinical experience, a comprehensive assessment of the risks and benefits of an AED can be made.
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| 9. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies
- 2016
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Ingår i: Neurology. - 0028-3878. ; 87:3, s. 314-323
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16-80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8 -week baseline and a 12 -week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%-29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%-31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%-31.8%) for 200 mg/d (p < 0.00001). The >50% responder rate was 34.2% (50 mg/d, p 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment -emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in >5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS.
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| 10. |
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| 11. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Epilepsi
- 2011
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Ingår i: Läkemedelsboken 2011-2012. - Uppsala. : Läkemedelsverket. - 9789197960502 ; , s. 965-76
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Bokkapitel (refereegranskat)
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| 12. |
- Ben-Menachem, Elinor, 1945
(författare)
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Epilepsy as a warning sign for stroke.
- 2005
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 5:1, s. 42-3
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Tidskriftsartikel (refereegranskat)
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| 13. |
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| 14. |
- Ben-Menachem, Elinor, 1945
(författare)
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Eslicarbazepine acetate: a well-kept secret?
- 2010
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Ingår i: Epilepsy currents. - : SAGE Publications. - 1535-7511 .- 1535-7597. ; 10:1, s. 7-8
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1–2 antiepileptic drugs (AEDs). METHODS: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n= 102) or once-daily ESL 400 mg (n= 100), 800 mg (n= 98), or 1,200 mg (n= 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). RESULTS: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p= 0.0003) and 800-mg (p= 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56–62% of patients), lamotrigine (25–27%), and valproic acid (22–28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. DISCUSSION: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.
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| 15. |
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| 16. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Guidelines--are they useful?
- 2006
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 47:Suppl 1, s. 62-4
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Tidskriftsartikel (refereegranskat)abstract
- Antiepileptic drug (AED) guidelines are developed to improve medical decision making, to provide guidance and recommendation for patient management, to develop standards to judge or assess clinical practice, and to keep the cost-benefit ratio at an acceptable level. These guidelines are derived from evidence-based medicine (EBM), a four-tiered grading system that is used to analyze clinical trials and published experiments independent of clinical bias and experience. Although guidelines may not answer all questions it is critical that clinicians using them consider the available evidence, as well as the quality of the evidence, when incorporating the information in their decision making.
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| 17. |
- Ben-Menachem, Elinor, 1945
(författare)
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Infantile spasms and epilepsy currents.
- 2005
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 5:4, s. 157-8
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Tidskriftsartikel (refereegranskat)abstract
- The United Kingdom Infantile Spasms Study Comparing Vigabatrin with Prednisolone or Tetracosactide at 14 Days: A Multicentre, Randomised Controlled Trial Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP Lancet 2004;364:1773–1778 Infantile spasms, a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms. Methods The United Kingdom Infantile Spasms Study assessed these treatments in a multicenter, randomized controlled trial in 150 hospitals in the United Kingdom. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin, 100 mg/kg/day; oral prednisolone, 40 mg/day; or intramuscular tetracosactide depot, 0.5 mg (40 IU) on alternate days. Analysis was by intention to treat. Results Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin ( n = 52) or hormonal treatments (prednisolone, n = 30; tetracosactide, n = 25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were 40 (73%) of 55 infants assigned hormonal treatments (prednisolone, 21 of 30 [70%]; tetracosactide, 19 of 25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference, 19%; 95% CI, 1%–36%, p = 0.043). Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants receiving hormonal treatments and 28 (54%) of 52 infants receiving vigabatrin. No deaths were recorded. Conclusions Cessation of spasms was more likely in infants given hormonal treatments than in those given vigabatrin. Adverse events were common with both treatments.
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| 18. |
- Ben-Menachem, Elinor, 1945
(författare)
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Introduction
- 2013
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 127, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 19. |
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| 20. |
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| 21. |
- Ben-Menachem, Elinor, 1945
(författare)
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Is prolactin a clinically useful measure of epilepsy?
- 2006
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 6:3, s. 78-9
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Tidskriftsartikel (refereegranskat)abstract
- Use of Serum Prolactin in Diagnosing Epileptic Seizures: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Chen DK, So YT, Fisher RS Neurology 2005;65(5):668–675 (Review) The purpose of this article is to review the use of serum prolactin assay in epileptic seizure diagnosis. Methods The authors identified relevant studies in multiple databases and reference lists. Studies that met inclusion criteria were summarized and rated for quality of evidence, and the results were analyzed and pooled where appropriate. Results Most studies used a serum prolactin of at least twice baseline value as abnormal. For the differentiation of epileptic seizures from psychogenic nonepileptic seizures, one Class I and seven Class II studies showed that elevated serum prolactin was highly predictive of either generalized tonic–clonic or complex partial seizures. Pooled sensitivity was higher for generalized tonic–clonic seizures (60.0%) than for complex partial seizures (46.1%), while the pooled specificity was similar for both (approximately 96%). Data were insufficient to establish validity for simple partial seizures. Two Class II studies were consistent in showing prolactin elevation after tilt-test–induced syncope. Inconclusive data exist regarding the value of serum prolactin following status epilepticus, repetitive seizures, and neonatal seizures. Recommendations Elevated serum prolactin assay, when measured in the appropriate clinical setting at 10 to 20 minutes after a suspected event, is a useful adjunct for the differentiation of generalized tonic–clonic or complex partial seizure from psychogenic nonepileptic seizure among adults and older children (Level B). Serum prolactin assay does not distinguish epileptic seizures from syncope (Level B). The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).
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| 22. |
- Ben-Menachem, Elinor, 1945
(författare)
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Is topiramate tops?
- 2008
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 8:3, s. 60-1
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Tidskriftsartikel (refereegranskat)abstract
- TOPIRAMATE MONOTHERAPY IN NEWLY DIAGNOSED EPILEPSY IN CHILDREN AND ADOLESCENTS: Glauser TA, Dlugos DJ, Dodson WE, Grinspan A, Wang S, Wu SC EPMN-106/INT-28 Investigators. J Child Neurol2007226:693-69917641254 A double-blind, dose-controlled study evaluated topiramate as monotherapy in 470 patients with newly diagnosed (3 months) epilepsy or epilepsy relapse in the absence of therapy. In addition to having at least 2 lifetime-unprovoked seizures, patients had 1 or 2 partial-onset seizures or generalized-onset tonic-clonic seizures during a 3-month retrospective baseline. The trial included a large cohort (N = 151, 32%) of children and adolescents 6 to 15 years of age. Eligible patients were randomized to treatment groups in which topiramate was titrated to target maintenance dosages of either 400 mg/day (n = 77) or 50 mg/day (n = 74). Patients were followed for at least 6 months. Based on Kaplan-Meier analyses, the primary efficacy endpoint of time to first seizure favored the higher topiramate dose in both the overall population and the cohort of children/adolescents. The probability that children/adolescents remaining in the study were seizure free at 6 months was 78% in the 50-mg target dose group and 90% with the higher dose. At 12 months, the probability of being seizure free was 62% and 85%, respectively. The incidence of treatment-limiting adverse events was 4% in the 50-mg target dose group and 14% in the group assigned to 400 mg as a target dose. The most common adverse events, excluding typical childhood illnesses, were headache, appetite decrease, weight loss, somnolence, dizziness, concentration/attention difficulty, and paresthesia. As shown in this subset analysis, topiramate is effective and well tolerated as monotherapy in children and adolescents.
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| 23. |
- Ben-Menachem, Elinor, 1945
(författare)
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Lacosamide: an investigational drug for adjunctive treatment of partial-onset seizures.
- 2008
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Ingår i: Drugs of today (Barcelona, Spain : 1998). - : Clarivate Analytics (US). - 1699-3993. ; 44:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- Lacosamide, (R)-2-acetamido-N-benzyl-3-meth- oxypropionamide, is a new chemical entity specifically synthesized as an anticonvulsive drug candidate, which appears to have a novel dual mode of action. Its pharmacokinetic characteristics have been studied in young and elderly healthy adults, as well as in adults with epilepsy or diabetic neuropathic pain. After oral administration, lacosamide is rapidly and completely absorbed. An elimination half-life of 13 hours allows for twice-daily dosing. Lacosamide has a low potential for drug-drug interactions. Both oral and intravenous formulations of lacosamide are being developed. In completed placebo-controlled clinical trials, lacosamide has demonstrated efficacy as adjunctive therapy for reduction of seizure frequency in patients with uncontrolled partial-onset seizures, and has been generally well tolerated. For patients treated with lacosamide, the most frequently reported adverse events in placebo-controlled trials include dizziness, headache, nausea and diplopia. When used as short-term replacement for oral lacosamide, intravenous lacosamide has a comparable safety profile to oral lacosamide. Results from clinical trials to date suggest that lacosamide may be a useful pharmacological treatment option for patients with partial-onset seizures.
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| 24. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Long-term safety and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy
- 2019
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 60:12, s. 2437-2447
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A large-scale, double-blind trial (SP0993; NCT01243177) demonstrated that lacosamide was noninferior to controlled-release carbamazepine (carbamazepine-CR) in terms of efficacy, and well tolerated as first-line monotherapy in patients (≥16years of age) with newly diagnosed epilepsy. We report primary safety outcomes from the double-blind extension of the noninferiority trial (SP0994; NCT01465997) and post hoc analyses of pooled long-term safety and efficacy data from both trials. Methods: Patients were randomized 1:1 to lacosamide or carbamazepine-CR. Doses were escalated (lacosamide: 200/400/600mg/d; carbamazepine-CR: 400/800/1200mg/d) based on seizure control. Eligible patients continued randomized treatment in the extension. Primary outcomes of the extension were treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Post hoc analyses of data from combined trials included 12- and 24-month seizure freedom and TEAEs by number of comorbid conditions. Results: A total of 886 patients were treated in the initial trial and 548 in the extension; 211 of 279 patients (75.6%) on lacosamide and 180/269 (66.9%) on carbamazepine-CR completed the extension. In the extension, 181 patients(64.9%) on lacosamide and 182 (67.7%) on carbamazepine-CR reported TEAEs; in both groups, nasopharyngitis, headache, and dizziness were most common. Serious TEAEs were reported by 32 patients (11.5%) on lacosamide and 22 (8.2%) on carbamazepine-CR; 12 (4.3%) and 21 (7.8%) discontinued due to TEAEs. In the combined trials (median exposure: lacosamide 630days; carbamazepine-CR 589days), Kaplan-Meier estimated proportions of patients with 12- and 24-month seizure freedom from first dose were 50.8% (95% confidence interval 46.2%-55.4%) and 47.0% (42.2%-51.7%) on lacosamide, and 54.9% (50.3%-59.6%) and 50.9% (46.0%-55.7%) on carbamazepine-CR. Incidences of drug-related TEAEs and discontinuations due to TEAEs increased by number of comorbid conditions and were lower in patients on lacosamide. Significance: Long-term (median~2years) lacosamide monotherapy was efficacious and generally well tolerated in adults with newly diagnosed epilepsy. Seizurefreedom rates were similar with lacosamide and carbamazepine-CR. © 2019 UCB Biopharma SPRL. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
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| 25. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Long-term safety and tolerability of lacosamide monotherapy in patients with epilepsy: Results from a multicenter, open-label trial
- 2021
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Ingår i: Epilepsia Open. - : Wiley. - 2470-9239. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this trial (SP1042; NCT02582866) was to assess long-term safety and tolerability of lacosamide monotherapy (200-600 mg/day) in adults with focal (partial-onset) seizures or generalized tonic-clonic seizures (without clear focal origin). This Phase III, long-term, open-label, multicenter, follow-up trial enrolled patients with epilepsy who were taking lacosamide in, and completed, the previous double-blind trial (SP0994; NCT01465997). Primary safety outcomes were treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, and serious TEAEs. One hundred and six patients were enrolled and received lacosamide: 84 (79.2%) completed the trial and 22 (20.8%) discontinued. The median duration of exposure was 854.0 days, with a median modal dose of 200 mg/day. Ninety-six (90.6%), 64 (60.4%), and 44 (41.5%) patients had >= 12, >= 24, and >= 36 months of lacosamide exposure, respectively. At least one TEAE was reported by 61 (57.5%) patients. The most common (>= 4%) TEAEs were headache (10 [9.4%]), nasopharyngitis (eight [7.5%]), and back pain (five [4.7%]). One (0.9%) patient discontinued due to a TEAE (sudden unexpected death in epilepsy; not considered drug-related), 14 (13.2%) patients reported serious TEAEs, and seven (6.6%) patients reported TEAEs that were considered drug-related. Overall, long-term lacosamide monotherapy was generally well tolerated up to 600 mg/day, with no new safety signals identified.
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| 26. |
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| 27. |
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| 28. |
- Ben-Menachem, Elinor, 1945
(författare)
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Medical management of refractory epilepsy-Practical treatment with novel antiepileptic drugs
- 2014
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Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 55, s. 3-8
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Tidskriftsartikel (refereegranskat)abstract
- The ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of differential diagnosis and adherence. Epilepsy surgery as an alternative therapy may be suitable in selected cases. If the diagnosis of epilepsy is established and epilepsy surgery is not appropriate, AED treatment should be optimized. Evidence for how to proceed is lacking. Concepts such as rational polytherapy have been advocated but remain speculative concerning better efficacy based on the use of AEDs with differing modes of action. A variety of new AEDs including rufinamide, lacosamide, vigabatrin, perampanel, and retigabine have been recently introduced in the United States. They are briefly characterized in this update review.
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| 29. |
- Ben-Menachem, Elinor, 1945
(författare)
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Neurostimulation - Past, Present, and Beyond
- 2012
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Ingår i: Epilepsy Currents. - : SAGE Publications. - 1535-7597 .- 1535-7511. ; 12:5, s. 188-191
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Tidskriftsartikel (refereegranskat)abstract
- Neurostimulation as a treatment for epilepsy has been around for almost 20 years in the form of vagus nerve stimulation. Newer types of neurostimulation are being developed and stand on the brink of approval for use. The two newest therapies, not yet approved in the United States, are deep brain stimulation and the Responsive Neurostimulator System . In fact, in Europe, approval has already been given for deep brain stimulation and newer forms of vagus nerve stimulation. Efficacy is similar between these therapies, and side effects are moderate, so what will be the future? The challenge will be to learn how to use these therapies correctly and offer the right treatment for the right patient.
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| 30. |
- Ben-Menachem, Elinor, 1945
(författare)
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Outcomes remain ambivalent for deep brain stimulation and epilepsy.
- 2008
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 8:5, s. 121-3
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Tidskriftsartikel (refereegranskat)abstract
- DEEP BRAIN STIMULATION IN PATIENTS WITH REFRACTORY TEMPORAL LOBE EPILEPSY: Boon P, Vonck K, De Herdt V, Van Dycke A, Goethals M, Goossens L, Van Zandijcke M, De Smedt T, Dewaele I, Achten R, Wadman W, Dewaele F, Caemaert J, Van Roost D. Epilepsia2007488:1551-156017726798 PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12-52 months), one of 10 stimulated patients are seizure-free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of >/=50%; two of 10 patients had a seizure-frequency reduction of 30-49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.
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| 31. |
- Ben-Menachem, Elinor, 1945
(författare)
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Partial Onset Seizure Treatment with Adjunctive Lacosamide in Epileptic Adults: A Review
- 2015
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Ingår i: Epilepsi. - : AVES YAYINCILIK A.Ş.. - 1300-7157. ; 21:1, s. 1-5
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Forskningsöversikt (refereegranskat)abstract
- Epilepsy is a common chronic disorder of the brain and can be seen at all ages with a higher prevalence in developing countries. Adjunctive therapy with antiepileptic drugs (AEDs) is the gold standard in treatment of epilepsy. Lacosamide (LCM) is a novel AED which is approved for adjunctive therapy for the treatment of partial- onset seizures. Recently 3 Phase II/III placebo controlled clinical trials with similar designs were conducted to investigate the efficacy and safety of lacosamide (LCM) administered as adjunctive therapy with other AEDs. Data collected from those studies were pooled, re- analyzed and presented in this review article. Results revealed that LCM is well tolerated and effective in seizure reduction as adjunctive therapy in patients with uncontrolled partial- onset seizures.
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| 32. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Predictors of weight loss in adults with topiramate-treated epilepsy.
- 2003
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Ingår i: Obesity research. - 1071-7323. ; 11:4, s. 556-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults. RESEARCH METHODS AND PROCEDURES: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial-onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment. RESULTS: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) >/= 30 kg/m(2)], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007). DISCUSSION: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.
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| 33. |
- Ben-Menachem, Elinor, 1945
(författare)
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Pregabalin pharmacology and its relevance to clinical practice.
- 2004
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 45 Suppl 6, s. 13-8
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Forskningsöversikt (refereegranskat)abstract
- Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. In addition, pregabalin has been shown to be a highly effective adjunctive therapy for partial seizures in clinical trials. Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. Pregabalin demonstrates highly predictable and linear pharmacokinetics, a profile that makes it easy to use in clinical practice. Absorption is extensive, rapid, and proportional to dose. Time to maximal plasma concentration is approximately 1 h and steady state is achieved within 24-48 h. These characteristics reflect the observed onset of efficacy as early as day two in clinical trials. High bioavailability, a mean elimination half life (t(1/2)) of 6.3 h, and dose-proportional maximal plasma concentrations and total exposures predict a dose-response relationship in clinical practice and allow an effective starting dose of 150 mg/day in clinical practice without need for titration. Administration with food has no clinically relevant effect on the amount of pregabalin absorbed, providing for a dosing regimen uncomplicated by meals. Pregabalin does not bind to plasma proteins and is excreted virtually unchanged (<2% metabolism) by the kidneys. It is not subject to hepatic metabolism and does not induce or inhibit liver enzymes such as the cytochrome P450 system. Therefore, pregabalin is unlikely to cause, or be subject to, pharmacokinetic drug-drug interactions--an expectation that has been confirmed in clinical pharmacokinetic studies. However, dose adjustment may be necessary in patients with renal insufficiency. Thus, the pharmacological and pharmacokinetic profiles of pregabalin provide a predictable basis for its use in clinical practice.
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| 34. |
- Ben-Menachem, Elinor, 1945
(författare)
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Retigabine: has the orphan found a home?
- 2007
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 7:6, s. 153-4
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Tidskriftsartikel (refereegranskat)abstract
- Randomized, Multicenter, Dose-Ranging Trial of Retigabine for Partial-Onset Seizures. Porter RJ, Partiot A, Sachdeo R, Nohria V, Alves WM; 205 Study Group. Neurology 2007;68(15):1197–1204. OBJECTIVE: To evaluate the efficacy and safety of retigabine 600, 900, and 1,200 mg/day administered three times daily as adjunctive therapy in patients with partial-onset seizures. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was performed. After an 8-week baseline phase, patients were randomized to a 16-week double-blind treatment period (8-week forced titration and 8-week maintenance) followed by either tapering or entry into an open-label extension study. Primary efficacy was the percentage change from baseline in monthly seizure frequency and compared across treatment arms. Secondary efficacy comparisons included the proportion of patients experiencing 50% reduction in seizure frequency (responder rate), emergence of new seizure types, and physician assessment of global clinical improvement. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluations. Efficacy analyses were performed on the intent-to-treat population. RESULTS: Of the 399 randomized patients, 279 (69.9%) completed the double-blind treatment period. The median percent change in monthly total partial seizure frequency from baseline was −23% for 600 mg/day, −29% for 900 mg/day, and −35% for 1,200 mg/day vs −13% for placebo ( p < 0.001 for overall difference across all treatment arms). Responder rates for retigabine were 23% for 600 mg/day, 32% for 900 mg/day ( p = 0.021), and 33% for 1,200 mg/day ( p = 0.016), vs 16% for placebo. The most common treatment-emergent AEs were somnolence, dizziness, confusion, speech disorder, vertigo, tremor, amnesia, abnormal thinking, abnormal gait, paresthesia, and diplopia. CONCLUSION: Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.
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| 35. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Role of valproate across the ages. Treatment of epilepsy in adults.
- 2006
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Ingår i: Acta neurologica Scandinavica. Supplementum. - : Hindawi Limited. - 0065-1427 .- 0001-6314 .- 1600-0404. ; 184, s. 14-27
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Forskningsöversikt (refereegranskat)abstract
- A workshop was held in Göteborg in June 2005 to discuss the place of valproate in treating adult epilepsies. Consensus positions were developed on the epilepsy types for which the drug is most suitable and the use of valproate in women of child-bearing age, in men and in patients with psychiatric comorbidity. Valproate was considered to be effective across a broad variety of epilepsy syndromes and seizure types and should be considered a suitable choice for first-line monotherapy of juvenile myoclonic epilepsy and other idiopathic generalized epilepsies. The use of valproate by women of child-bearing age is associated with potential harm to the foetus. A conservative approach to treatment is recommended in these patients whereby alternative antiepileptic drugs should be proposed to women planning pregnancies wherever satisfactory seizure control can be thereby maintained. In cases where valproate is used during pregnancy, either because the pregnancy was unplanned or because alternative treatment options of equivalent efficacy are unavailable, appropriate counselling, precautionary measures and monitoring should be provided. The evidence for an impact of valproate on male reproductive health is equivocal and considerations of male fertility should not be taken into account in deciding whether to prescribe valproate to men. Valproate can be proposed safely to patients with comorbid psychiatric disease or underlying psychiatric vulnerability.
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| 36. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial
- 2021
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 170
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Tidskriftsartikel (refereegranskat)abstract
- This long-term open-label extension (OLE) trial was conducted to evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses in patients with epilepsy and focal (partial-onset) or generalized onset seizures, or Unverricht-Lundborg disease (ULD). A secondary objective was to evaluate efficacy of BRV in the subgroups of patients with focal or generalized onset seizures. Patients with epilepsy were eligible to enroll in this OLE (N01125; NCT00175916) and were analyzed if they had completed a previous double-blind BRV trial (N01114 [NCT00175929], N01252 [NCT00490035], N01254 [NCT00504881], N01187 [NCT00357669], and N01236 [NCT00368251]), and were expected to obtain a reasonable benefit from long-term BRV treatment. Patients entered the OLE at the BRV dose recommended at the end of the previous trial, with dose adjustments of BRV and concomitant antiseizure medications permitted. Safety variables included treatment-emergent adverse events (TEAEs). Efficacy variables in patients with focal seizures were percent reduction in focal seizure frequency, 50 % responder rates, and 6- and 12-month seizure-freedom. Eight hundred and fifty-three patients (729 [85.5 %] with focal seizures, 30 [3.5 %] with generalized onset seizures, and 94 [11.0 %] with ULD) were enrolled and included in the Safety Set. Overall, 619 (72.6 %) patients discontinued the trial, mainly due to lack of efficacy (354 [41.5 %]), adverse events (100 [11.7 %]), and patient choice (98 [11.5 %]). During the OLE, 588 (68.9 %) patients received BRV for >= 12 months, 403 (47.2 %) for >= 36 months, and 223 (26.1 %) for >= 96 months. The most common modal dose of BRV was 150 mg/day (415 [48.7 %] patients). In the ULD subgroup, the most common modal BRV dose was 100 mg/day (44/94 [46.8 %] patients), and 37/94 (39.4 %) patients had >= 96 months of BRV exposure. Overall, 720/853 (84.4 %) patients reported TEAEs, 451 (52.9 %) had a drug-related TEAE, and 95 (11.1 %) discontinued BRV due to a TEAE. In the ULD subgroup, 87/94 (92.6 %) patients reported TEAEs, 60 (63.8 %) had a drug-related TEAE, and 16 (17.0 %) discontinued due to a TEAE. In patients with focal seizures, the median reduction in focal seizure frequency from Baseline was 43.1 % (n = 728), the 50 % responder rate was 43.6 % (n = 729), and 6-and 12-month seizure freedom rates were 22.2 % and 15.8 %, respectively (n = 595). Overall, BRV was well-tolerated as long-term adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease, with improvements in focal seizure frequency maintained over time.
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| 37. |
- Ben-Menachem, Elinor, 1945
(författare)
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Seizure aggravation-evidence that oxcarbazepine requires monitoring.
- 2008
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 8:4, s. 93-5
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Tidskriftsartikel (refereegranskat)abstract
- AGGRAVATION OF SEIZURES AND/OR EEG FEATURES IN CHILDREN TREATED WITH OXCARBAZEPINE MONOTHERAPY: Vendrame M, Khurana DS, Cruz M, Melvin J, Valencia I, Legido A, Kothare SV Epilepsia20074811:2116-212017645535 Epub 2007 Jul 21. PURPOSE: Exacerbation of epilepsy may occur following initiation of therapy with antiepileptic drugs (AEDs). The aim of this study is to analyze the clinical and EEG characteristics of a group of pediatric patients with worsening of seizures and/or EEG deterioration while on oxcarbazepine (OXC). METHODS: A retrospective analysis of a clinical database was performed to identify patients with epilepsy treated with OXC over the past 3 years. History, neurological examination, and EEG findings were reviewed to identify any who had developed exacerbation of seizures or new abnormalities on EEG. RESULTS: Of 290 patients on OXC, we identified 12 patients with new onset seizures, all with initial normal neurological exam and normal EEG, who developed either worsening of preexisting seizures, new seizure types, and/or EEG deterioration following introduction of OXC monotherapy. EEG changes were primarily characterized by new onset of generalized epileptiform activity not reported on the initial baseline EEG. Following substitution of OXC with a broad spectrum AED, significant improvement of seizure control and improvement in the EEG was observed. CONCLUSIONS: These findings suggest that OXC can aggravate seizures and/or worsen EEG features in children. Following initiation of therapy with OXC, monitoring of patients with follow-up EEGs may be important, especially in patients who do not show adequate response to therapy.
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| 38. |
- Ben-Menachem, Elinor, 1945
(författare)
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Some Long Awaited Answers Regarding Seizures during Pregnancy.
- 2009
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 9:1, s. 16-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Seizure Control in Antiepileptic Drug-Treated Pregnancy. Vajda FJ, Hitchcock A, Graham J, O'Brien T, Lander C, Eadie M. Epilepsia 2008;49(1):172–176. This brief report covers an analysis of 7 years outcome data from the Australian Register of Antiepileptic Drugs in Pregnancy. In studying the control of antiepileptic drug-treated epileptic seizures during pregnancy, it was found that pregnancy had little influence on antiepileptic drug-treated epileptic seizure disorders. Seizures during pregnancy occurred in 49.7% of 841 antiepileptic drug (AED) treated pregnancies in women with epilepsy. Epilepsies that were active in the year before pregnancy tended to increase the risk of intrapartum and postpartum seizures. The risk of seizures during pregnancy was 50–70% less if the prepregnancy year was seizure-free, and decreased relatively little more with longer periods of prepregnancy seizure control. Once there had been 1 year's freedom from seizures there seemed relatively little further advantage in deferring pregnancy to avoid seizures returning while pregnant.
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| 39. |
- Ben-Menachem, Elinor, 1945
(författare)
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Strategy for utilization of new antiepileptic drugs.
- 2008
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Ingår i: Current opinion in neurology. - 1350-7540. ; 21:2, s. 167-72
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The paper reviews strategies to incorporate new antiepileptic drugs into the treatment arsenal for patients with epilepsy. RECENT FINDINGS: Ten new antiepileptic drugs have been developed in the last two decades, making selection of optimal therapy complex; they have not been shown to have better efficacy but generally seem to be better tolerated. Newer antiepileptic drugs offer new opportunities to patients who have not had a favorable response to the old ones. Many new antiepileptic drugs exhibit a broad spectrum of activity while only one of the older ones (valproate) has a broad-spectrum profile. There are therefore more choices when trying to match treatment with epileptic seizures and syndromes. The side-effect profiles of the newer antiepileptic drugs differ from the older ones with fewer systemic reactions and better pharmacokinetics for the most part. SUMMARY: Comparative studies are needed to elucidate the specific weaknesses and strengths of each of the new antiepileptic drugs compared with the older ones. Most clinical trials do not help the physician in deciding drug, dose, or titration schedules. Thus the physician needs to understand efficacy spectrum and side-effect profiles of each new antiepileptic drug in order to be able to treat each patient optimally.
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| 40. |
- Ben-Menachem, Elinor, 1945
(författare)
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Sudden death and epilepsy.
- 2005
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 5:6, s. 223-4
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Tidskriftsartikel (refereegranskat)abstract
- Case–control Study of SUDEP Langan Y, Nashef L, Sander JW Neurology 2005;64:1131–1133 To examine the influence of various factors on the risk of sudden unexpected death in epilepsy (SUDEP). Methods The authors investigated 154 cases in which a postmortem examination was performed. Each case had four controls with epilepsy from the community, matched for age and geographic location. Backward stepwise conditional logistic regression analysis was performed, and odds ratios for risk and protection were determined. Results The risk of SUDEP was increased with a history of generalized tonic–clonic seizures in the previous 3 months (odds ratio [OR]: 13.8; 95% CI: 6.6 to 29.1). The presence of supervision at night was found to be protective (OR: 0.4; 95% CI: 0.2 to 0.8) when a supervising individual shared the same bedroom or when special precautions such as a listening device were used (OR: 0.1; 95% CI: 0.0 to 0.3). Conclusions This work lends support to the view that SUDEP is a seizure-related phenomenon and that control of tonic–clonic seizures is important in its prevention. Nocturnal supervision seems to protect against SUDEP.
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| 41. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Surgically implanted and non-invasive vagus nerve stimulation: areview of efficacy, safety and tolerability
- 2015
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 22:9, s. 1260-1268
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Tidskriftsartikel (refereegranskat)abstract
- Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.
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| 42. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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The burden of chronic drug-refractory focal onset epilepsy: Can it be prevented?
- 2023
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Ingår i: Epilepsy & Behavior. - 1525-5050. ; 148
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Tidskriftsartikel (refereegranskat)abstract
- Despite the many therapeutic options for epilepsy available today, a third of patients still have poorly controlled epilepsy. Over the years, their transition through lines of treatment exposes them to increased risk of disease progression, mortality, morbidity, mental distress, and not least significantly impaired quality of life (QoL).The present review explores the multiple factors contributing to the impairment of health-related QoL in PWE-including both seizure-related and non seizure-related. The analysis aims to identify potential areas of intervention and strategies for a more holistic approach to epilepsy care and inform policymakers and healthcare providers in their approach to this condition.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 43. |
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| 44. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Topiramate monotherapy in the treatment of newly or recently diagnosed epilepsy.
- 2008
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Ingår i: Clinical therapeutics. - 0149-2918. ; 30:7, s. 1180-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The efficacy of topiramate (TPM) as an adjunctive treatment for epilepsy has been established in placebo-controlled clinical trials. Clinical trials of antiepileptic monotherapy usually evaluate low and high doses of study drug or compare study drug with another active agent. OBJECTIVE: This article reviews available evidence for the use of TPM as monotherapy in patients with newly or recently diagnosed epilepsy. METHODS: A search of MEDLINE, EMBASE, BIOSIS, SCISEARCH, and the Cochrane Database of Systematic Reviews (all years) for reports of controlled trials of TPM monotherapy in patients with recently diagnosed (within the previous 3 years) epilepsy was conducted in January 2008 using the terms topiramate, epilepsy, newly diagnosed, recently diagnosed, and monotherapy. Identified trials were included in the review if they were published in peer-reviewed journals and enrolled > or = 20 patients. RESULTS: Three randomized, double-blind, controlled trials met the criteria for inclusion in the review. In a comparison of TPM 50 and 500 mg/d, the higher dose was associated with significantly greater freedom from seizures at 6 months compared with the lower dose (54% vs 39%, respectively; P = 0.02). The time to first seizure was significantly associated with mean plasma TPM concentrations (P = 0.015). In a comparison of TPM 50 and 400 mg/d, the time to first seizure was significantly longer with the higher dose compared with the lower dose (P<0.001, Kaplan-Meier analysis), and the probability of 12-month seizure freedom was significantly higher (76% vs 59%, respectively; P = 0.001). Again, the time to first seizure was significantly associated with mean plasma TPM concentrations (P = 0.029). In a comparative study of TPM 100 and 200 mg/d, carbamazepine 600 mg/d, and valproate 1250 mg/d, there was no significant difference in rates of 6-month seizure freedom with TPM 100 and 200 mg/d (49% and 44%, respectively), carbamazepine (44%), and valproate (44%). Adverse events in the 3 studies were similar between TPM dose groups, although the incidence generally increased with increasing doses, occurred early in treatment, and decreased with prolonged therapy. In a pooled analysis of the 3 trials, the most commonly occurring adverse events during dose titration were paresthesia (25%), fatigue (16%), dizziness (13%), somnolence (13%), and nausea (10%); the most frequent adverse events during maintenance therapy were headache (20%), decreased appetite (11%), and weight loss (11%). CONCLUSION: In the 3 studies reviewed, TPM monotherapy was effective and generally well tolerated in patients with newly diagnosed epilepsy.
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| 46. |
- Ben-Menachem, Elinor, 1945
(författare)
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Treatment of new onset seizures: predicting long-term outcome.
- 2006
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 6:6, s. 184-5
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of Risk of Seizure Recurrence after a Single Seizure and Early Epilepsy: Further Results from the MESS Trial Kim LG, Johnson TL, Marson AG, Chadwick DW; MRC MESS Study group Lancet Neurol 2006;5:317–322. Erratum in: Lancet Neurol 2006;5:383 The MRC Multicentre trial for Early Epilepsy and Single Seizures (MESS) showed a reduced risk of further seizures in patients, for whom treatment with antiepileptic drugs was uncertain, who were randomly assigned immediate treatment compared with delayed treatment. However, there was no evidence of long-term remission rates. This study was undertaken to assess the role of patient characteristics and treatment in the prediction of seizure recurrence. This will enable decision making on the basis of the perceived risk of treatment compared with the benefit of reducing the risk of further seizures in the initial years after diagnosis. Methods A prognostic model was developed based on individual patient data from MESS to enable identification of patients at low, medium, or high risk of seizure recurrence. A split-sample approach was used in which the model was developed on a subsample of the full data and validated on the remainder of the sample. Distinction of the prognostic groups and predictive accuracy of the model were assessed. Findings Number of seizures of all types at presentation, presence of a neurological disorder, and an abnormal electroencephalogram (EEG) were significant factors in indicating future seizures. Individuals with two or three seizures, a neurological disorder, or an abnormal EEG were identified as the medium-risk group, those with two of these features or more than three seizures as the high-risk group, and those with a single seizure only as the low-risk group. Interpretation The model shows that there is little benefit to immediate treatment in patients at low risk of seizure recurrence, but potentially worthwhile benefits are seen in those at medium and high risk.
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| 47. |
- Ben-Menachem, Elinor, 1945
(författare)
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Vaccination and the onset of dravet syndrome.
- 2011
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Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7511. ; 11:4, s. 120-2
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Tidskriftsartikel (refereegranskat)
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| 48. |
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| 49. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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VNS Therapy versus the latest antiepileptic drug.
- 2005
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Ingår i: Epileptic disorders : international epilepsy journal with videotape. - 1294-9361. ; 7 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Pro AED: The central issue in medical decision-making is risk-benefit assessment. Surgery of any type is still considered to be a major undertaking. To warrant these risks, the patient has a right to expect that they have a greater chance of a good outcome with an invasive therapy than with a non-invasive one. The main question is when, if ever, this becomes the case when comparing implantation of a VNS Therapy System versus adding an antiepileptic drug (AED)? After the first drug? The second? After all AEDs have failed? To date, no randomized trial comparing the addition of an AED against vagus nerve stimulation (VNS Therapy) has been undertaken, although several are currently being contemplated. Without this information, it is more difficult to make a case for early implementation of VNS Therapy. Unfortunately, few data are available regarding the potential for patients to become seizure-free after implantation of a VNS Therapy System. Another issue is side effects. It is important to remember that VNS Therapy also produces adverse events, albeit very different in character than those associated with AEDs, to which physicians have become accustomed. These include cough, dyspnea, pharyngitis, voice alteration and sleep apnea. A less frequently discussed, potentially negative consequence of VNS Therapy relates to the ability to obtain imaging of the patient. Patients who have undergone VNS Therapy System implantation are not candidates for imaging of the chest, breast, or abdomen. A second issue is that imaging of the brain can only be performed with MRI scanners that meet certain requirements, and as MRI technology develops, scanners meeting these requirements may become harder to find. However, to summarize, VNS Therapy is an excellent and useful treatment choice. Fortunately, the choice between AEDs and VNS Therapy is not an "either/or" decision. Each has a role in the treatment of patients with epilepsy, and the advantages and disadvantages of each should be kept in perspective. Pro VNS Therapy: VNS Therapy is no longer a new treatment for patients with refractory epilepsy. The first implant was performed in l988, and since then more than 30,000 patients have received this therapy. It is no longer considered an unusual or dangerous procedure, but it is still used almost exclusively for refractory epilepsy patients and it has not been generally accepted for use as a first line or even second line therapy. However, compared to the new AEDs, VNS Therapy has similar efficacy results in clinical trials and in many epilepsy syndromes and the long-term efficacy results are even more positive, with continued improvement in seizure reduction for up to two years. Two of the major reasons for not using VNS Therapy early are that it is a surgical procedure, and its safety during MRI procedures, especially with 3 Tesla, has not yet been elucidated. The safety profile of VNS Therapy is very favorable; the side effects being totally different from those seen with AEDs. The most important aspects are that there have been no pharmacological interactions, cognitive or sedative side effects reported, and it is safe for use in all age groups. Side effects are restricted to local irritation, hoarseness, coughing and, in a few cases, swallowing difficulties when the stimulator is on, but these tend to disappear with time. No idiosyncratic side effect has emerged during the 16 years of use. Compliance is guaranteed. The cost of the implantation of the VNS Therapy System, when spread out over 8 years (battery life), is actually less than the cost of using a new AED over an eight-year period, and real savings as regards hospital costs due to seizures can be expected.
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| 50. |
- Ben-Menachem, Elinor, 1945
(författare)
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Weight issues for people with epilepsy : a review.
- 2007
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 48:Suppl 9, s. 42-5
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Tidskriftsartikel (refereegranskat)abstract
- Weight gain or loss is not an integral part of epilepsy although a sedentary lifestyle can contribute to weight gain. Pharmacological treatment for epilepsy may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. Antiepileptic drugs (AEDs) associated with weight loss are felbamate, topiramate, and zonisamide. AEDs associated with weight gain are gabapentin, pregabalin, valproic acid, and vigabatrin and possibly, carbamazepine. Weight neutral AEDs are lamotrigine, levetiracetam, and phenytoin. In clinical practice it is critical to weigh patients regularly and AED selection should be based on each patient's profile without sacrificing therapeutic efficacy.
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