Predictors for relapse after antiepileptic drug withdrawal in seizure-free patients with epilepsy

The objective of this study was to evaluate the timing of medication withdrawal and other clinical factors as potential predictors of seizure relapse after antiepileptic drug (AED) withdrawal in patients with epilepsy. A total of 99 patients who were seizure free for more than 2 years were recruited from the Neurology Clinics of Nanjing Brain Hospital between 2001 and 2009, and were followed prospectively for at least 2 years or until seizure relapse. Kaplan–Meier survival analysis was used for calculating recurrence rates. Univariate and multivariate analyses for recurrence risk factors were performed using the Cox proportional hazards model. Thirteen patients were excluded due to loss of follow-up or incomplete seizure records. Epileptiform electroencephalography (EEG) abnormality within the first year after AED withdrawal (hazard ratio [HR] = 4.810, 95% confidence interval [CI] = 2.220–10.420) was found on multivariate analysis to be a predictor of seizure recurrence. Early AED withdrawal after a seizure-free period of 2–3 years did not significantly increase the risk of recurrence (HR = 0.999, 95% CI = 0.969–1.029) as compared with delayed AED withdrawal (patients who were seizure-free for more than 3 years). AED can be withdrawn in patients who have been seizure-free for more than 2 years. As epileptiform EEG abnormality within the first year after AED withdrawal predicts seizure relapse, it is necessary to perform EEG for patients during the first year after AED withdrawal.     

Risk of recurrence after drug withdrawal in childhood epilepsy

ObjectivesAfter a reasonable seizure-free period, discontinuation of antiepileptic drugs (AED) is usually decided in epileptic patients despite the risk of seizure recurrence. In children, risk of recurrence after discontinuation of AED is generally 20–40%; however, there is still no general agreement on the criteria to predict safe discontinuation. This study was designed to determine the risk of recurrence and related risk factors after drug withdrawal in epileptic children.Methods200 epileptic patients between 1 month and 15 years of age who were followed at least 1 year after drug withdrawal at a child neurology center between January 1993 and December 2005 formed the study population of this retrospective study. Patients were classified into groups according to defined risk factors for recurrence.ResultsOf 200 patients (118 boys, 82 girls), overall recurrence rate was 27%. Girls were more likely to have a seizure recurrence than boys, with the difference approaching statistical significance (p = 0.058). EEG recordings after withdrawal (post-withdrawal EEG) in the follow-up were significantly different in the patients with recurrence with respect to presence of an abnormality (p = 0.05). In the multivariate Cox regression analysis, female gender and abnormal post-withdrawal EEG were the risk factors influencing seizure recurrence, with female gender identified as the main risk factor.ConclusionsAlthough the decision to discontinue AED treatment necessitates evaluation of each patient individually, our study suggests that female patients and those with abnormal EEG after withdrawal require more cautious follow-up because of the high risk of recurrence.     

Benign mesial temporal lobe epilepsy: A clinical cohort and literature review

ObjectiveWe present a single-center retrospective study of benign mesial temporal lobe epilepsy (bMTLE) between 1995 and 2014.MethodsHospital records and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG), imaging features, and response to treatment with antiepileptic drugs (AEDs) were documented. Patients were included in this study if they were seizure-free for a minimum of 24 months with or without an AED.ResultsTwenty-seven patients were identified. There were 19 (70%) females, mean age at first seizure was 32.2 (range: 15–80 years). In all patients, seizures were mild, and seizure freedom was readily achieved with the initiation of AED therapy. Sixteen patients (59%) had mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue AED therapy after a prolonged period of remission (5–8 years), but all had seizure recurrence within 2 to 4 weeks.SignificanceNot all temporal lobe epilepsy is refractory to medication, despite the presence of MTS. Until clinical trials indicate otherwise, surgery is not indicated but life-long medical treatment is advocated.     

Is antiepileptic drug withdrawal status related to quality of life in seizure-free adult patients with epilepsy?

PurposeThis study aimed to determine factors that influence the quality of life (QOL) of seizure-free adult patients with epilepsy in western China and address whether these determinants vary by antiepileptic drug (AED) withdrawal.MethodsA cross-sectional study was conducted in the epilepsy outpatient clinic of West China Hospital, Sichuan University. Patients with epilepsy who were aged at least 18 years and seizure-free for at least 12 months were interviewed using the Quality of Life in Epilepsy Inventory-31 (QOLIE-31); the National Hospital Seizure Severity Scale (NHS3); the Liverpool Adverse Events Profile (LAEP); the Social Support Rating Scale (SSRS); the Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) Questionnaire; and the Scale of Knowledge and Attitudes Toward Epilepsy. Eligible patients were divided into two groups: the nonwithdrawal group and the withdrawal group. The independent-samples t-test was used to compare the QOL between the groups, and linear regression analysis was used to explain the variance of their QOL.ResultsOne hundred and eighty-seven (135 nonwithdrawal and 52 withdrawal) patients were included in the analysis. The QOLIE-31 overall score of the nonwithdrawal group was lower than that of the withdrawal group (p < 0.01). The LAEP score was the strongest predictor of the QOLIE-31 overall score of all subjects, explaining 26.9% of the variance. The second strongest predictor was the SSRS score, explaining 12.9%, and the other predictors were the NHS3 score (5.2%), education level (2.3%), age (1.5%), and marriage (1.0%). Furthermore, the strongest predictors in the nonwithdrawal group were the LAEP and SSRS scores, while in the withdrawal group, the strongest predictors were stigma scores and employment.ConclusionAmong the seizure-free adult patients with epilepsy, those with AED withdrawal experienced better QOL than those continuing AED treatment. Furthermore, the determinants of QOL varied by AED withdrawal. Individual strategies to optimize QOL should be developed based on these differences.     

Discontinuation of antiepileptic drugs after successful epilepsy surgery

OBJECTIVE: To evaluate the frequency and risk factors for seizure recurrence subsequent to antiepileptic drug (AED) withdrawal in patients who underwent surgical treatment for intractable partial epilepsy and were rendered seizure-free. METHODS: The outcome of discontinuation of AED medication was studied retrospectively in 210 consecutive patients who were rendered seizure-free after epilepsy surgery performed between 1989 and 1993. RESULTS: Medical therapy was reduced in 96 patients and discontinued in 84 patients. The seizure recurrence rate after complete AED withdrawal was 14% and 36% at 2 and 5 years. In contrast, only 3% and 7% of the 30 patients who did not alter AED treatment after surgery had recurrent seizures in the same time intervals. After AED discontinuation, seizures tended to recur more often in patients with normal preoperative MRI studies compared with those with focal pathology. However, this difference did not reach significance. Intraoperative electrocorticography, extent of surgical resection, postoperative EEG, and seizure-free duration after surgery were not predictive of seizure outcome after AED withdrawal. CONCLUSIONS: AED withdrawal was associated with seizure recurrence in a significant portion of patients rendered seizure-free by epilepsy surgery. Patients with a normal preoperative MRI study showed a tendency for higher seizure recurrence, whereas the duration of seizure-free postoperative AED treatment interval did not significantly influence the seizure recurrence rate. These results will prove useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.     

Lacosamide in patients with temporal lobe epilepsy: An observational multicentric open-label study

PurposeThe aim of this study was to evaluate the efficacy and tolerability of lacosamide (LCM) both as add-on therapy and monotherapy in patients with temporal lobe epilepsy (TLE) based on an observational, prospective, multicenter study.MethodsWe enrolled 100 patients (mean age: 43.4 ± 12.53 years, 57 females) with nonlesional TLE and TLE with hippocampal sclerosis (HS) that did not respond to the first drug and who were referred to epilepsy centers of the University of Catanzaro, University of Palermo, IRCSS Neuromed of Pozzilli, and Otto-von-Guericke University of Magdeburg. In this open-label, multicenter trial, patients were initiated on oral LCM as add-on therapy to first AED monotherapy or as a later add-on to two concomitant AEDs. Seizure frequency changes and adverse events were recorded for at least six months after LCM was added.ResultsFourteen patients dropped out because of positive MRI findings other than HS. Patients received LCM at 200–400 mg/day. Fifty-eight out of these 86 patients with seizures that were previously drug-resistant had reduced seizure frequency after introduction of LCM. Forty-five out of 86 patients were classified as responders (12 were seizure-free, 33 achieved a reduction > 50%). Interestingly, five patients out of 86 achieved seizure freedom for at least one year and progressively switched to monotherapy with LCM, and all five remained seizure-free at follow-up (6–48 months).ConclusionsOur results may suggest that LCM at doses of 200 to 400 mg/day reduces seizure frequency in adults with TLE regardless of the presence of HS, and that it may be considered as a first add-on treatment for patients with pharmacoresistant TLE.     

Clinical and economic burden of breakthrough seizures

PurposeThe purpose of this study was to measure health-care resource utilization and costs in treatment-adherent, previously seizure-free patients with epilepsy who were treated in the inpatient/emergency room (ER) setting for new-onset seizures, compared with matched controls.MethodsThe study used a retrospective case/control study design using administrative claims from the IMS PharMetrics™ database. We identified adult patients with epilepsy with 1 + ER visit/hospitalization with primary diagnosis of epilepsy between 1/1/2006 and 3/31/2011, preceded by 6 months of seizure-free activity and antiepileptic drug (AED) treatment adherence (≥ 80% of days covered by any AED); the first observed seizure defined the “breakthrough” seizure/index event. Treatment-adherent patients with epilepsy without any ER/hospital admission for seizures served as controls: an outpatient epilepsy-related medical claim within the selection window was chosen at random as the index date. The following were continuous enrollment requirements for all patients: ≥ 12-month pre- and ≥ 6-month postindex. Each case matched 1:1 to a control using propensity score matching. All-cause and epilepsy-related (epilepsy/convulsion diagnosis, AED pharmacy) resource utilization and unadjusted and adjusted direct health-care costs (per person, 2012 US dollars (USD)) were assessed in a 6-month follow-up period.Principal resultsThere were 5729 cases and 14,437 controls eligible. The final sample comprised 5279 matched case/control pairs. In unadjusted analyses, matched cases had significantly higher rates of all-cause hospitalization and ER visits compared to controls and significantly higher total all-cause direct health-care costs (median $12,714 vs. $5095, p < 0.001) and total epilepsy-related costs among cases vs. controls (median $7293 vs. $1712, p < 0.001), driven by higher inpatient costs. Among cases, costs increased with each subsequent seizure (driven by inpatient costs). Cases had 2.3 times higher adjusted all-cause costs and 8.1 times higher adjusted epilepsy-related costs than controls (both p < 0.001).ConclusionInpatient/ER-treated breakthrough seizures occurred among 28.4% of our treatment-adherent study sample and were associated with significant incremental health-care utilization and costs, primarily driven by hospitalizations. Our findings suggest the need for better seizure control via optimal patient management and the use of effective AED therapy, which can potentially lower health-care costs.     

What do epileptologists recommend about discontinuing antiepileptic drugs for a second time in children?

ObjectiveThere is a broad consensus that antiepileptic drugs (AEDs) may be withdrawn after two years of seizure freedom for most children with epilepsy. If seizures recur and are, again, completely controlled with AEDs, little is known about discontinuing a second time. We surveyed American and Canadian pediatric epileptologists to understand their current practice.MethodsIn 2014, a survey was sent via e-mail to 193 pediatric epileptologists to learn about AED discontinuation practices in children. The survey asked direct questions about practice and posed five “real-life” cases where the decision to discontinue might be difficult. Participants were identified through membership lists of several US and Canadian epilepsy organizations.ResultsThere were 94 (49%) completed surveys. Sixty-three participants had ≥ 10 years in practice (“more experienced”: mean 23 ± 9 years), and 31 had < 10 years (“less experienced”: mean 6 ± 2). Overall, 62% recommended AED discontinuation for the first time after 2–3 years of seizure freedom, and 61% recommended discontinuation for the second time after 2–3 years. Fifty-six percent of “more experienced” clinicians required a longer seizure-free period prior to a second discontinuation (p < 0.001) compared with 26% of “less experienced” clinicians (p = ns). Overall, most participants suggested an AED taper duration of 2–6 months for the first and second attempts, 52% and 68%, respectively. Both groups wean AEDs more slowly during the second attempt (p < 0.001). There was only 40–60% agreement among participants to discontinue AEDs in four of the cases.ConclusionNearly half (46%) of pediatric epileptologists require a longer seizure-free period the second time they attempt to discontinue AEDs compared with the first attempt and wean down AEDs somewhat more slowly. Although a variety of factors influence decision-making, there was a high level of disagreement to discontinue AEDs a second time in “real-life” cases.     

Retention rate of pregabalin in drug-resistant epilepsy: 1-year follow-up, single-centre observation in 105 consecutive, adult patients

ObjectivesPregabalin (PGB) is a newer antiepileptic drug (AED) licensed as add-on treatment for partial epilepsy in adults. Efficacy and safety have been proven in several controlled clinical studies. These trials, however, only partially reflect clinical practice. Retention rate has been established as a marker for efficacy and safety of AEDs in long-term follow-up studies.MethodsWe evaluated the data of the first 105 patients treated with PGB at Bethel Epilepsy Centre, a tertiary referral centre for epilepsy. The patients were interviewed after 3, 6 and 12 months.Results105 adult patients (aged 38 ± 13 years) were treated with PGB, on average in combination with 2.1 AEDs (mean observation period 232 days). 76.2% had focal epilepsy, 19.0 multifocal epilepsy, and 3.8% epilepsy with both focal and generalised seizures. 40% continued PGB with the following outcome: 5.7% seizure-free for at least 1 month (4.8% for at least 3 months, 2.4% for at least 6 months; one of the seizure-free patients, however, had had epilepsy surgery during the observational period), 17.1% responders (≥50% reduction of seizure frequency but not seizure-free), 13.3% with unchanged or increased seizure frequency. Reasons for withdrawal were lack of efficacy (47.6%) or side-effects (12.7%).ConclusionsPGB is a new therapeutic option as add-on therapy for patients with highly refractory focal epilepsies although the therapeutic success that can be expected in this group of patients is limited.     

Rufinamide for refractory focal seizures: An open-label,multicenter European study

PurposeThe present study aimed to assess the efficacy and tolerability of rufinamide as adjunctive drug for the treatment of a large series of children, adolescents and adults with refractory cryptogenic or symptomatic focal epilepsy.MethodsPatients were recruited in a prospective, add-on, open-label treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care. Inclusion criteria were: (1) age 3 years or more; (2) diagnosis of cryptogenic or symptomatic focal epilepsy refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination; (3) more than one seizure per month in the last 6 months; (4) use of at least one other AED, but no more than three, at baseline; (5) informed consent from parents and/or caregivers.ResultsSixty-eight patients (40 males, 28 females), aged between 3 and 63 years (mean 19.9 years, median 16.0) ± SD 12.58, with cryptogenic (28 pts, 41.2%) or symptomatic focal epilepsy (40 pts, 58.8%), were recruited in the study. After a mean follow-up period of 10.4 ± 10.29 months, twenty-two patients (32.3%) had a 50–99% seizure reduction, and none became seizure-free. Twelve patients (17.6%) had a 25–49% seizure decrease, while in 30 (44.1%) seizure frequency was unchanged. A seizure worsening was reported in 5 patients (7.3%). A better response to rufinamide occurred in frontal lobe seizures (51.6%) and secondary generalized tonic–clonic seizures (50%).ConclusionRufinamide was effective against focal-onset seizures, particularly in the treatment of secondary generalized frontal lobe seizures.     

NEOPLASM study: Real-life use of lacosamide in patients with brain tumor-related epilepsy

BackgroundThe choice of antiepileptic drug (AED) therapy in patients with brain tumor-related epilepsy (BTRE) is complicated, and there are a lack of robust clinical trial data to date.MethodsThe NEOPLASM (Neuroncologic Patients treated with LAcoSaMide) study was a 6-month, multicenter, retrospective, observational study in patients with BTRE treated with lacosamide. Patients were started on lacosamide because of a lack of efficacy or adverse events (AEs) with prior AEDs or suitability versus other AEDs, according to clinical practice. The primary efficacy variable was the seizure-free rate at 6 months. Safety variables included the proportion of patients with an AE and the proportion with an AE that led to discontinuation.ResultsOverall, 105 patients from 14 hospital centers were included in the analysis. Treatment with lacosamide for 6 months resulted in a 30.8% seizure-free rate, and 66.3% of patients had a ≥ 50% seizure reduction (responders). In the subset of patients included because of a lack of efficacy with prior AEDs, seizure-free rates were 28.0%, and 66.7% of patients were responders. No statistically significant differences in efficacy were observed according to the mechanism of action or enzyme-inducing properties of concomitant AEDs. Adverse events were reported by 41.9% of patients at 6 months, and 4.7% of them led to discontinuation. The most common AEs were somnolence/fatigue and dizziness. Notably, 57.1% of the patients who were switched to lacosamide because of AEs with their previous therapy did not report any AE at 6-month follow-up.ConclusionsIn this open-label, observational study, lacosamide appeared to be effective and well tolerated in a large population of patients with BTRE. Lacosamide may therefore be a promising option for the treatment of patients with BTRE.     

Risk factors for recurrence after drug withdrawal in childhood epilepsy

BackgroundSeveral studies have been conducted to determine the risk of recurrence after withdrawal of antiepileptic drugs (AEDs) in recent years. There is no consensus concerning the circumstances affecting discontinuation of AEDs. This study was designed to determine the recurrence rate of epilepsy after withdrawal of AEDs and the risk factors related with recurrence.MethodsChildren with epilepsy onset between 1 month and 16 years of age who were followed up at least 3 years after AED treatment withdrawal were enrolled. Patients were classified into groups according to defined risk factors for recurrence.ResultsA total of 284 patients, 137 (48.2%) girls and 147 (51.8%) boys were included, and seizures recurred after withdrawal in 51 patients (18%). Thirty-three (64.7%) patients had recurrence in the first year after withdrawal. The recurrence risk was calculated based on the electro-clinical syndromes classification; the recurrence risk was the highest in the juvenile myoclonic/absence group and lowest in the benign infantile seizure group. No recurrence was observed in the infantile spasm group. Data evaluated by multivariable analysis showed that having the structural-metabolic and unknown epilepsy and <3 years seizure free period before withdrawal of AEDs were the main risk factors for recurrence after AED withdrawal in our study.ConclusionWe suggest a seizure-free period of at least 3 years under AED medication and we must be cautious in patients with structural-metabolic and unknown epilepsy before AED withdrawal.     

The relationship of depression to antiepileptic drug adherence and quality of life in epilepsy

We sought to examine the impact of depression upon antiepileptic drug (AED) adherence in patients with epilepsy. We administered the Center for Epidemiologic Studies Depression Scale (CES-D), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Seizure Severity Questionnaire (SSQ), and Quality of Life in Epilepsy-10 (QOLIE-10) and measured AED adherence by utilizing the medication possession ratio (MPR) in adult patients with epilepsy identified through a pharmacy claims database. From a sampling frame of over 10,000 patients identified in claims, 2750 were randomly selected and contacted directly by mail to participate in the cross-sectional survey. A total of 465 eligible patients completed a survey. Survey data were combined with administrative claims data for analysis. We conducted a path analysis to assess the relationships between depression, adherence, seizure severity, and quality of life (QOL). Patients with depression scored significantly worse on measures of seizure severity (p = .003), QOL (p < .001), and adherence (p = .001). On path analysis, depression and QOL and seizure severity and QOL were related, but only the NDDI-E scores had a significant relationship with medication adherence (p = .001). Depression as measured by the NDDI-E was correlated with an increased risk of AED nonadherence. Depression or seizure severity adversely impacted QOL. These results demonstrate yet another important reason to screen for depression in epilepsy.     

A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures

This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12 months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥ 65 years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28 days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥ 2) at baseline. Patients who added lacosamide took a modal dose of 200 mg/day over the treatment period (n = 501), and 50.1% (256/511) completed 12 months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all < 65 years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were reported by four patients who added lacosamide (two cases of depression, two of suicide attempt) and one who added another AED (depression). Seven deaths occurred, all of which were considered unrelated/unlikely related to study medication. This thorough evaluation revealed a low incidence of predefined CV- and psychiatric-related TEAEs in patients taking adjunctive AED therapy according to standard medical practice. No specific safety concerns related to adjunctive lacosamide therapy were noted.     

Remission of epilepsy as a function of time

The modalities and mechanisms of remission in epilepsy are largely unknown apart from certain self-limited syndromes. In an earlier investigation, therapeutic antiepileptic drug (AED) plasma levels were used as biomarkers of seizure propensity, and their course was monitored during slow stepwise drug withdrawal in seizure-free patients. The findings indicated that remission typically was a slow quantitative process taking place over time. It was not possible to determine if this process was limited to an individual endpoint or continuous and open-ended. The present study addresses this question with 17 patients who in the previous study had suffered a relapse but participated in a second and, in some cases, third attempt to terminate treatment. Earlier relapse did not predict the outcome. Seven patients became seizure-free without drugs, five are seizure-free on a reduced dose and, only five required the same dose as before the second reduction. Thus, whereas remission in some cases is only partial and limited, in others, it appears as a slow but continuous process. In a prototypical example of idiopathic generalized epilepsy, terminal remission was reached after 27 years of treatment. We conclude that, in these cases, remission of epilepsy is primarily a function of time.     

Patient emotions and perceptions of antiepileptic drug changes and titration during treatment for epilepsy

ObjectiveTo investigate the impact of antiepileptic drug (AED) change and dose titration on the emotional well-being of patients with epilepsy.MethodsMembers of an online epilepsy community were invited to voluntarily participate in an online survey. The cross-sectional anonymous survey consisted of 31 multiple choice questions balanced in terms of variety and positivity/negativity of emotions concerning participants' most recent AED change. To substantiate survey results, spontaneous comments from epilepsy-related online forums and social media websites that mentioned participants' experiences with AED medication changes (termed passive listening statements) were analyzed and categorized by theme.ResultsAll 345 survey participants (270 [78.3%] female; 172 [49.9%] were 26–45 years old) self-reported an epilepsy/seizure diagnosis and were currently taking seizure medication; 263 (76.2%) were taking ≥ 2 AEDs and 301 (87.2%) had ≥ 1 seizure in the previous 18 months. All participants reported a medication change within the previous 12 months (dose increased [153 participants (44.3%)], medication added [105 (30.4%)], dose decreased [49 (14.2%)], medication removed [38 (11.0%)]). Improving seizure control (247 [71.6%]) and adverse events (109 [31.6%]) were the most common reasons for medication change. Primary emotions most associated (≥ 10% of participants) with an AED regimen change were (before medication change; during/after medication change) hopefulness (50 [14.5%]; 43 [12.5%]), uncertainty (50 [14.5%]; 69 [20.0%]), and anxiety (35 [10.1%]; 45 [13.0%]), and were largely due to concerns whether the change would work (212/345 [61.4%]; 180/345 [52.2%]). In the text analysis segment aimed at validating the survey, 230 participants' passive listening statements about medication titration were analyzed; additional seizure activity during dose titration (93 [40.4%]), adverse events during titration (71 [30.9%]), higher medication dosages (33 [14.3%]), and drug costs (25 [10.9%]) were the most commonly noted concerns.ConclusionAlthough the emotional well-being of patients with epilepsy is complex, our study results suggest that participants report their emotional well-being as negatively affected by changes in AED regimen, with most patients reporting uncertainty regarding the outcome of such a change. Future research is warranted to explore approaches to alleviate patient concerns associated with AED medication changes.     

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PurposeEpilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe.MethodsWe systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies.ResultsOverall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60 months, range 12–72); six patients (35.3%) were seizure free at least 12 month before observation points (median duration 120.5 months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p = 0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p = 0.116) and before reoperation (p = 0.622) was not poorer compared to patients with congruent Video-EEG results.ConclusionsReoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.     

Prospective audits with newer antiepileptic drugs in focal epilepsy: Insights into population responses?

Despite the availability of a wide range of new antiepileptic drugs (AEDs), there is little evidence that their introduction has substantially altered outcomes. This paper reviews data from 5 consecutive prospective audits with new AEDs using similar methodology. Prospective audits with topiramate (TPM; n = 135), levetiracetam (LEV; n = 136), zonisamide (ZNS; n = 141), pregabalin (PGB; n = 135), and lacosamide (LCM; n = 160) were undertaken in treated patients with uncontrolled partial-onset seizures. Follow-up continued until one of four endpoints was reached: seizure freedom for ≥ 6 months on unchanged dosing; ≥ 50% reduction (responder) in seizure frequency on the highest tolerated dose compared with baseline; < 50% seizure frequency reduction (marginal response) compared with baseline in patients wishing to continue treatment with the new AED; or withdrawal due to lack of efficacy, side effects, or both. A greater proportion of seizure-free patients occurred with LEV (23.5%), LCM (21.9%), and TPM (20.7%) than with ZNS (12.8%) and PGB (10.4%). A higher percentage discontinued treatment with ZNS (41.8%) and PGB (50.4%) than with LEV (32.4%), TPM (31.1%), and LCM (22.5%). Most seizure-free patients responded to the new agent as first or second add-on (TPM 96%; LEV 97%; ZNS 89%; PGB 86%; LCM 97%) often at modest or moderate dosing (TPM 68%, ≤ 200 mg/day; LEV 63%, ≤ 1000 mg/day; ZNS 61%, ≤ 100 mg/day; PGB 86%, ≤ 300 mg/day; LCM 74%, ≤ 200 mg/day). With < 10% of patients discontinuing all AEDs due to lack of efficacy, tolerability was the major factor influencing the number of patients remaining on treatment. Lacosamide was the best (77% patients continued treatment), while PGB was the worst (50% continued treatment) tolerated AED. Overall, seizure freedom was achieved in < 25% of patients in each audit, mainly as a first or second add-on, with best tolerated AEDs producing a higher number of good outcomes. Seizures in very few patients with drug-resistant epilepsy, as defined by the International League Against Epilepsy task force, responded to any of the 5 newer AEDs. These data support the suggestion that the introduction of modern agents has not importantly impacted the outcomes in refractory epilepsy.     

Drug withdrawal after successful epilepsy surgery: How safe is it?

Discontinuation of antiepileptic drugs (AEDs) is one reason patients undergo epilepsy surgery, but little is known about the risk of seizure recurrence. We describe a prospective pilot study of withdrawal performed at our epilepsy center. Sixty completely seizure-free patients were included between 1997 and 2003. AED withdrawal was proposed 1 year after surgery after a detailed discussion of the risks and benefits. On the basis of their decision on withdrawal, patients were stratified into two cohorts (withdrawal group, N = 34; control group, N = 26). Discontinuation was carried out in small tapering steps over 1 year with yearly follow-up visits. Withdrawal was stopped when seizures recurred or the patients objected to further discontinuation. Twenty-six of 34 (76.5%) persons in the withdrawal group and 16 of 26 (61.5%) persons in the control group were seizure free 5 years after surgery. In this study, AED discontinuation 1 year after successful epilepsy surgery was not associated with a risk of seizure recurrence higher than that of controls.