Antiepileptic Drug Withdrawal Research Articles

Early versus late antiepileptic drug withdrawal following temporal lobectomy

PurposeTo compare the seizure outcome following early and late complete antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). MethodAll the patients who were seizure free for one year following ATL were offered early or late AED withdrawal. AEDs were discontinued starting at one year in those who opted for early withdrawal. Patients who opted for late withdrawal were continued on single AED for three years following surgery before attempting complete discontinuation. ResultsOf the 135 study patients, 65 opted for early AED withdrawal and 70 for late withdrawal. The mean postoperative follow-up duration was 10.4 ± 1.3 (Range, 8–12) years. At three years following surgery, seizure recurrence occurred in 23 (35.4 %) patients in the early withdrawal group and in 10 (14.3 %) patients in late withdrawal group (p = 0.005; relative risk [RR], 2.48; 95 % confidence interval [CI], 1.28–4.80). At last follow-up, 27 (41.5 %) patients in the early withdrawal group and 26 (37.1 %) in late withdrawal group had recurrence (p = 0.60; RR, 1.12, 95 % CI, 0.74–1.70). At last followup, 80 (59.3 %) patients were off AEDs. During the terminal one year, 123 (91 %) patients were seizure free, similar in the two groups. ConclusionsThis nonrandomized controlled study suggests that early complete AED withdrawal starting one year following ATL is associated with a higher risk of early seizure recurrence. However, long term seizure outcome is similar in early and late AED withdrawal groups.

Relative Seizure Relapse Risks Associated with Antiepileptic Drug Withdrawal After Different Seizure-Free Periods in Adults with Focal Epilepsy: A Prospective, Controlled Follow-Up Study

Approximately two-thirds of patients with newly diagnosed epilepsy become seizure-free after antiepileptic drug (AED) treatment. A crucial issue for these patients and their families, especially after a long period of seizure freedom, is when to stop their medications. The aim of this study was to identify the optimal timing of AED withdrawal inadults with focal epilepsy who had been seizure-free for ≥ 2years. Adults with focal epilepsy who had been seizure-free for ≥ 2years were recruited. Based on their decision to discontinue (withdrawal) or continue (non-withdrawal) AED treatment, patients were assigned to withdrawal or non-withdrawal subgroups according to the length of remission (2 to < 3years, 3 to < 4years, 4 to < 5years and ≥ 5years). The relapse risks of the withdrawal and corresponding non-withdrawal subgroups were compared, and the relative relapse risks were assessed in a Cox proportional hazard regression model. A total of 213 eligible patients began to withdraw from AED treatment; 70 had been seizure-free for 2 to < 3years, 62 had been seizure-free for 3 to < 4years, 37 had been seizure-free for 4 to < 5years and 44 had been seizure-free for ≥ 5years. The figures for the corresponding non-withdrawal subgroups were 463, 334, 251 and 182, respectively. There was a significantly higher risk of seizure relapse in patients withdrawing from AEDs after 2 to < 5years of seizure freedom than in the corresponding non-withdrawal controls, and the relative relapse risk was 3.052 (95% confidence interval [CI] 2.126-4.381; p < 0.001) for the seizure-free period of 2 to < 3 years, 3.617 (95% CI2.384-5.488; p < 0.001) for 3 to < 4years and 2.644 (95% CI 1.456-4.799; p = 0.001) for 4 to < 5years. However, for patients who were seizure-free for ≥ 5years, AED withdrawal did not significantly increase the risk of seizure relapse compared with that of patients continuing treatment (hazard ratio [HR] 1.362, 95% CI 0.634-2.926, p = 0.428). Compared with a seizure-free period of 2 to < 3years, the relative relapse risk after AED withdrawal was significantly reduced only after being seizure-free for ≥ 5years (HR 0.441, 95% CI 0.233-0.834; p = 0.012). Overall, for adults with focal epilepsy, withdrawal from AEDs significantly increased the risk of seizure relapse after being seizure-free for 2 to < 5years, but might not increase the risk if the seizure-free period was ≥ 5years.

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.

Discontinuing antiepileptic drugs in long-standing idiopathic generalised epilepsy.

Once adults with long-standing idiopathic generalised epilepsy have achieved stable seizure remission, patients or physicians may attempt to discontinue their antiepileptic drug treatment. To date, risk of subsequent seizure relapse across the four idiopathic generalised epilepsy syndromes is largely unknown, and so are the clinical variables associated. For this retrospective observational study, 256 adult outpatients with idiopathic generalised epilepsy were evaluated. Data were obtained from outpatient charts and, if possible, from additional telephone or mail interviews. In 84 patients (33%), antiepileptic medication was discontinued at least once. Median patient age at antiepileptic drug withdrawal was 33years, and median duration of subsequent follow-up was 20years. Seizures recurred in 46% of patients after a median latency of 11months. Following multivariable analysis, seizure relapse was independently associated with short duration of seizure remission beforehand. If medication was withdrawn after < 5years of seizure freedom, two-thirds of patients had a seizure relapse, while among those in remission for ≥ 5years, only one-third relapsed. Discontinuation of antiepileptic drug treatment can be successful in every other adult with long-standing idiopathic generalised epilepsy. Short duration of prior seizure remission appears to be a relevant predictor of seizure recurrence.

Forced normalization: A systematic review.

Forced normalization (FN) is an intriguing phenomenon characterized by the emergence of psychiatric disturbances following the establishment of seizure control or reduction in the epileptic activity in a patient with previous uncontrolled epilepsy. We aim to describe the clinical characteristics of the condition. We conducted a systematic review on MEDLINE, EMBASE, Cochrane, and Scielo from January 1953 to January 2018. Clinical, electrographic, and imaging data were gathered. We considered all outcomes in children and adults. We performed no meta-analyses due to the limited available data. Of 2606 abstracts identified, 36 fulfilled the FN diagnostic criteria; 193 FN episodes were evaluated and 77 of them were analyzed extensively. Sixty percent of cases were female. Mean age ± standard deviation (SD) was 28.3±14.2years. The majority of patients had focal (80%) symptomatic (44%) epilepsy. Most patients reported a high ictal frequency (58%) and were on polytherapy (51%). Patients presented psychosis (86.4%), mood disorders (25.8%), and dissociation (4.5%) as the main manifestations. In the psychosis group, persecutory (52.6%) and reference (47.3%) delusions were frequent. FN was provoked by an antiepileptic drug (AED) (48.5%) mainly levetiracetam, epilepsy surgery (31.8%), or vagus nerve stimulation (13.6%). Treatment was homogeneous including anticonvulsant withdrawal (47%) or taper (25%); antipsychotics were initiated in the majority of cases (73%). Psychiatric symptoms were partially controlled in 35%, with complete resolution of symptoms in the remaining 65% of cases. The majority of patients (87%) with AED trigger and withdrawal presented complete resolution of symptoms in comparison to 28.5% of patients triggered by surgery. Forced normalization is an entity whose pathophysiology remains uncertain. Antipsychotic drug use does not predict complete resolution of psychiatric symptoms in comparison with AED withdrawal. Although there is a positive response to treatment in patients with FN triggered by drugs, the prognosis is obscure in patients with surgery triggered FN.

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30-year cohort study.

To evaluate the long-term pharmacological outcomes in teenagers with different epilepsies. This study included teenagers aged 13-19years at treatment initiation who were newly treated with antiepileptic drugs (AEDs) at the epilepsy unit of the Western Infirmary in Glasgow, Scotland, between 1 September 1982 and 30 September 2012. Patients were prospectively followed until 30 April 2016, or death, with at least a 2-year follow-up. A total of 332 adolescent patients (53% female; median age 16years; 54% with generalized epilepsy) were included. At the end of the study, 221 patients (67%) were seizure-free. A higher seizure-free rate was observed in those with generalized compared to focal epilepsy (72% versus 60%, P=0.01). During the study, 108 patients had relapses after periods of being seizure-free, most commonly due to poor adherence to AEDs (49%, n=53/108). AED withdrawal was associated with a high risk of seizure recurrence (70%, n=26/37), but 56% (n=61/108) of relapsed patients became seizure-free again by the end of the study, with only 9% (n=31/332) meeting the International League Against Epilepsy (ILAE) definition of pharmacoresistance during follow-up. Of the 221 seizure-free patients, 83% achieved this on monotherapy. There was no significant difference in efficacy rate between new and standard AED monotherapy (74% versus 77%, P=0.66). The overall poor tolerability rate of AEDs was 21% (n=69/332). Among the different new and standard AEDs used as initial monotherapy, lamotrigine was associated with the lowest rate of adverse effects (12%, n=15/124), while topiramate was associated with the highest rate (56%, n=5/9). Teenagers with epilepsy showed good seizure control, particularly those with generalized epilepsy. However, relapse was common and there was high risk of seizure recurrence after treatment withdrawal. Most patients were controlled on monotherapy. As the efficacy of AEDs was comparable, tolerability can be a primary consideration for AED selection in this population.

Correlation between EEG during AED withdrawal and epilepsy recurrence: a meta-analysis.

To assess the risk of epilepsy recurrence after withdrawal from antiepileptic drugs (AEDs), researchers extensively studied recurrence-related risk factors, including electroencephalogram (EEG) during AED withdrawal. The relationship between EEG and epilepsy recurrence is controversial. We used meta-analysis to determine the correlation between EEG during AED withdrawal and epilepsy recurrence. A total of seven studies met the criteria for inclusion. The Newcastle-Ottawa Scale was used to conduct the research quality evaluation. Seven hundred three patients were included in meta-analysis. Patients with abnormal EEGs during withdrawal had a higher recurrence rate than patients with normal EEGs. Abnormal EEGs during withdrawal were a risk factor for recurrence.

Antiepileptic Drug Treatment of Epilepsy in Children.

The treatment of epilepsy in children is highly individualized at each and every major step in the management. This review examines various factors that modify the treatment from the point of initiation of therapy to the decision to stop an antiepileptic drug (AED). AED therapy leads to seizure freedom in about 70% of all children with epilepsy. AED initiation could be delayed until a second seizure in most children and may be avoided altogether in many children with self-limited childhood focal epilepsies. Three key factors influence the choice of AED: seizure type(s), efficacy of the drug for the seizure type, and the side effect profile of the drug(s). For epileptic spasms, steroids and vigabatrin are the most effective treatment options. For absence seizures, ethosuximide and valproic acid are superior to lamotrigine. For focal seizures, many newer AEDs have favorable side effect profiles with efficacy comparable to older-generation drugs. For generalized epilepsies, valproic acid remains the most effective drug for a broad range of seizure types. Genetic and metabolic etiologies may guide unique treatment choices in some children. After 2 years or more of seizure freedom, if the recurrence risk after AED withdrawal is acceptable, slow weaning of AEDs should be done over the span of 6 weeks or longer. After discontinuation, about 70% of patients remain seizure free, and of those with recurrence, the majority achieve seizure control with restarting an AED. When treatment with two or more AEDs fails, other treatment opportunities for drug-resistant epilepsy, including epilepsy surgery, vagal nerve stimulation, and dietary therapies should be considered. Carefully selected medical therapy guided by seizure type and AED characteristics is effective in more than two-thirds of children with epilepsy.

Impact of withdrawal of antiepileptic medication on the duration of focal onset seizures

PurposeTo systematically evaluate the duration of focal onset seizures under medication withdrawal as a function of drug half-life. MethodsAdults with drug resistant focal epilepsy and invasive electroencephalographic (iEEG) recording between 01/2006 and 06/2016 (n = 128) were identified. Patients with multifocal or unknown epileptic foci were excluded, as well as subclinical seizures, isolated auras, or status epileptic. Antiepileptic drugs (AEDs) were withdrawn upon admission. The seizure duration was determined based on the invasive EEG data, and the latency since start of the monitoring was noted in hours. A negative binomial mixed model was used to compare the seizure durations before and after a cut-off, which was set at 2.5 half-lives of the individual anticonvulsive medication as this is thought to separate therapeutic and ineffective drug levels. ResultsIn total, 70 patients were included in the study and the duration of 672 seizures analyzed. On average, the patients were treated with 2.36 ± 0.78 AEDs. The individual cut-off of 2.5 half-lives was on average reached after 95.02 ± 80.18 h. The seizure frequency (321 vs. 351) and the rate of generalization (15.6% vs. 16.8%) was comparable before and after the individual cut-off point. The mean seizure duration was not statistically significantly prolonged after 2.5 half-lives by a factor of 1.168 for focal onset seizures (p = 0.090) and a factor of 1.091 for secondary generalized seizures (p = 0.545). ConclusionsAlthough AED withdrawal increases the likelihood for epileptic seizures, it did not prolong the seizure duration, nor did it increase the rate of secondary generalization in our study.

Recurrence of Seizure after Antiepileptic Drug Withdrawal in Children with Epilepsy

Recurrence of Seizure after Antiepileptic Drug Withdrawal in Children with Epilepsy

Editors' note: Outcome after seizure recurrence on antiepileptic drug withdrawal following temporal lobectomy

Dr. Rathore et al. evaluated outcome after seizure recurrence during antiepileptic drug (AED) withdrawal following temporal lobectomy and found that despite initial seizure recurrence, 86% of patients become seizure-free and 18% become drug-free. Dr. Sethi commends the study's long postoperative follow-up of 12 years, but notes that every patient with temporal lobe epilepsy is unique and treatment decisions must be individualized. Drs. Rathore and Jeyaraj agree that medication management after temporal lobectomy should be personalized, but reiterate that withdrawal of AEDs is one of the goals of epilepsy surgery. They recommend use of the FND20 score described in their article to assist in determining which patients are ideal candidates for withdrawal of medications, but emphasize that this score does not provide absolute certainty about successful outcome following discontinuation of AEDs. Dr. Rathore et al. evaluated outcome after seizure recurrence during antiepileptic drug (AED) withdrawal following temporal lobectomy and found that despite initial seizure recurrence, 86% of patients become seizure-free and 18% become drug-free. Dr. Sethi commends the study's long postoperative follow-up of 12 years, but notes that every patient with temporal lobe epilepsy is unique and treatment decisions must be individualized.

Reader response: Outcome after seizure recurrence on antiepileptic drug withdrawal following temporal lobectomy.

I read with interest the article by Rathore et al.1 on outcome after seizure recurrence in patients on antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). The authors are to be lauded for their long postoperative follow-up of 12 years, which helped delineate the natural history of these postoperative patients. The take-home message, if replicated in future studies, is that these patients do well whether or not they have seizures after initial attempted AED withdrawal. In medicine, every patient is an n of one trial (clinical trial in which a single patient is the entire trial). No 2 patients with MTLE are exactly the same, and the decision to taper off AED after ATL has to be individualized based on a number of epilepsy-centric factors (type of seizures: complex partial vs partial with secondary generalization, extent of resection, presence or absence of interictal epileptiform discharges on EEG after ATL) and patient-centric factors (functional status of patient, living status of patient [alone or with family members], driving status), among others.

Author response: Outcome after seizure recurrence on antiepileptic drug withdrawal following temporal lobectomy.

We thank Dr. Sethi for reemphasizing our view that decision to withdraw antiepileptic drugs (AEDs) after temporal lobectomy needs to be individualized and requires multifactorial consideration.1 Even one recurrence in these patients, who otherwise consider themselves as cured, can be upsetting. However, it is also true that the majority of these patients want to discontinue their AED, and this, in fact, is one of the major aims of epilepsy surgery.2 This is even more true in developing countries due to the social stigma and financial burden associated with continued AED use. In this scenario, it is useful to identify factors that can predict successful AED withdrawal. The FND20 score delineated in our study can be a useful guide for identifying ideal candidates for AED withdrawal.1 However, this score is not absolute and many other factors also play a role in deciding successful AED withdrawal. The other important question that arises while planning AED withdrawal is the risk of subsequent uncontrolled epilepsy. In this regard, our study is reassuring that the majority of patients, who have seizure recurrence on AED withdrawal, subsequently become seizure-free and there is no concern of precipitating resistant epilepsy.

Withdrawal of antiepileptic drugs in patients with low grade and anaplastic glioma after long-term seizure freedom: a prospective observational study

BackgroundWhen glioma patients experience long-term seizure freedom the question arises whether antiepileptic drugs (AEDs) should be continued. As no prospective studies exist on seizure recurrence in glioma patients after AED withdrawal, we evaluated the decision-making process to withdraw AEDs in glioma patients, and seizure outcome after withdrawal.MethodsPatients with a histologically confirmed low grade or anaplastic glioma were included. Eligible patients were seizure free ≥ 1 year from the date of last antitumor treatment, or ≥ 2 years since the last seizure when seizures occurred after the end of the last antitumor treatment. Patients and neuro-oncologists made a shared decision on the preferred AED treatment (i.e. AED withdrawal or continuation). Primary outcomes were: (1) outcome of the shared decision-making process and (2) rate of seizure recurrence.ResultsEighty-three patients fulfilled all eligibility criteria. However, in 12/83 (14%) patients, the neuro-oncologist had serious objections to AED withdrawal. Therefore, 71/83 (86%) patients were analyzed; In 46/71 (65%) patients it was decided to withdraw AED treatment. In the withdrawal group, 26% (12/46) had seizure recurrence during follow-up. Seven of these 12 patients (58%) had tumor progression, of which three within 3 months after seizure recurrence. In the AED continuation group, 8% (2/25) of patients had seizure recurrence of which one had tumor progression.ConclusionIn 65% of patients a shared decision was made to withdraw AEDs, of which 26% had seizure recurrence. AED withdrawal should only be considered in carefully selected patients with a presumed low risk of tumor progression.

Reader response: Incidence of MS has increased markedly over 6 decades in Denmark particularly with late onset and in women.

Dr. Rathore et al. evaluated outcome after seizure recurrence during antiepileptic drug (AED) withdrawal following temporal lobectomy and found that despite initial seizure recurrence, 86% of patients become seizure-free and 18% become drug-free. Dr. Sethi commends the study's long postoperative follow-up of 12 years, but notes that every patient with temporal lobe epilepsy is unique and treatment decisions must be individualized. Drs. Rathore and Jeyaraj agree that medication management after temporal lobectomy should be personalized, but reiterate that withdrawal of AEDs is one of the goals of epilepsy surgery. They recommend use of the FND20 score described in their article to assist in determining which patients are ideal candidates for withdrawal of medications, but emphasize that this score does not provide absolute certainty about successful outcome following discontinuation of AEDs.

Chapter 10 - Ambulatory EEG

Ambulatory electroencephalography (aEEG) is a technique of continuous EEG recording while ensuring maximum mobility of the patient in a more naturalistic setting. The initial technological drawbacks of aEEG have been circumvented by incorporating digital and computer technology. Some of the current devices provide the facility of synchronous video recording. Low cost, convenience, higher diagnostic yield, and the ability to capture circadian patterns are the main advantages of aEEG. It is a useful tool in the diagnosis of epilepsy and nonepileptic paroxysmal disorders. Ambulatory EEG is superior to routine EEG in capturing interictal epileptiform abnormalities particularly in relation to natural sleep. However, the use of aEEG in presurgical workup is still unclear and more research is needed. At present, the place of EEG in the decision making for antiepileptic drug withdrawal is unclear and aEEG is an ideal tool to study this research question. Well-designed studies are needed to evaluate the use of aEEG in the assessment of response to antiepileptic therapy and occupational safety. Ambulatory EEG is an underutilized tool and more research is needed to expand the horizon of its applications in clinical practice.

Antiepileptic Drug Withdrawal after Surgery in Children with Focal Cortical Dysplasia: Seizure Recurrence and Its Predictors.

Background and PurposeThis study investigated the seizure recurrence rate and potential predictors of seizure recurrence following antiepileptic drug (AED) withdrawal after resective epilepsy surgery in children with focal cortical dysplasia (FCD).MethodsWe retrospectively analyzed the records of 70 children and adolescents with FCD types I, II, and IIIa who underwent resective epilepsy surgery between 2004 and 2015 and were followed for at least 2 years after surgery.ResultsWe attempted AED withdrawal in 40 patients. The median time of starting the AED reduction was 10.8 months after surgery. Of these 40 patients, 14 patients (35%) experienced seizure recurrence during AED reduction or after AED withdrawal. Half of the 14 patients who experienced recurrence regained seizure freedom after AED reintroduction and optimization. Compared with their preoperative status, the AED dose or number was decreased in 57.1% of patients, and remained unchanged in 14.3% after surgery. A multivariate analysis found that incomplete resection (p=0.004) and epileptic discharges on the postoperative EEG (p=0.025) were important predictors of seizure recurrence after AED withdrawal. Over the mean follow-up duration of 4.5 years after surgery, 34 patients (48.6% of the entire cohort) were seizure-free with and without AEDs.ConclusionsChildren with incomplete resection and epileptic discharges on postoperative EEG are at a high risk of seizure recurrence after drug withdrawal. Complete resection of FCD may lead to a favorable surgical outcome and successful AED withdrawal after surgery.

Antiepileptic drug withdrawal in juvenile myoclonic epilepsy.

Withdrawal of antiepileptic drugs (AEDs) has been discouraged in juvenile myoclonic epilepsy (JME). However, impulsivity as a consequence of executive dysfunction in JME may influence treatment adherence. The aim of the present study was to assess how common withdrawal of AEDs is in a large and representative JME group. Patients with genetic generalized epilepsy (GGE) were identified through a retrospective search of medical records at Drammen Hospital, Norway, and invited to a clinical interview. Information related to AED withdrawal was analyzed in those classified as JME. A total of 132 patients with GGE were interviewed (87 JME). Thirty-five patients with JME (40%) discontinued AEDs, of which 74% did so without consulting a doctor. The rate of self-withdrawal was significantly higher in JME than in other types of GGE. Having a parent with psychosocial difficulties was significantly over-represented in the JME self-withdrawal group. Twelve of those who discontinued AEDs (34%) were free from generalized tonic-clonic seizures (GTCS) and without antiepileptic drugs >1year. All but one of them withdrew AEDs without consulting a doctor. Age at first motor seizure was significantly higher in those with a favorable outcome of AED withdrawal. Self-withdrawal of AEDs is common in JME, especially in those with troublesome conditions at home. However, about 1/3 may remain free from GTCS without AEDs. The findings indicate a need for a stronger follow-up with appropriate information about the prognosis of the disorder.

Long-term outcome of seizure-free patients and risk factors of relapse following antiepileptic drug withdrawal

ObjectiveThis study aimed to investigate the long-term outcome in seizure-free patients and to explore the risk factors of seizure relapse following antiepileptic drug (AED) withdrawal. MethodsThis study included 161 patients who had been seizure-free for at least 2 years. These patients were monitored over a follow-up period of at least 3 years or until seizure relapse after AED withdrawal. Patients were grouped into a seizure-free group and a relapse group. Risk factors of seizure relapse were analyzed. ResultsDuring the follow-up period, 72 patients (44.7%) relapsed while 89 patients (55.3%) did not. The average time of relapse was 19.12 ± 27.17 months after the initiation of AED withdrawal, and majority of cases occurred within the first 24 months of AED withdrawal (73.6%). Univariate analysis showed that the likelihood of relapse was higher in patients with uncontrolled seizures beyond the first 6 months of AED therapy initiation, patients with a history of perinatal injury, patients with multiple seizure types, and patients who had been treated with a combination of AEDs. Multiple logistic regression analysis revealed that uncontrolled seizures beyond the first 6 months of AED treatment and a history of perinatal injury were independent risk factors of seizure relapse. ConclusionIn the majority of cases, epilepsy relapse occurred within the first two years after the initiation of AED withdrawal. The independent risk factors of seizure relapse were uncontrolled seizures beyond the first 6 months of AED therapy and cases with a history of perinatal injury.

Why the TimeToStop trial failed to recruit: a survey on antiepileptic drug withdrawal after paediatric epilepsy surgery.

Following the results of the multicentre European retrospective "TimeToStop" cohort study, we initiated a randomised trial to determine cognitive benefits of early postoperative antiepileptic drug withdrawal. Unfortunately, the trial failed to recruit and was terminated, as almost all parents preferred early drug withdrawal. The objectives of the current survey were to obtain insight into current practices regarding drug withdrawal after paediatric epilepsy surgery among epileptologists, and better understand the reasons for difficulties in recruitment. A survey was sent to three international epilepsy surgery networks, questioning drug withdrawal policies. Forty-seven (19%) surveys were returned. For polytherapy, withdrawal was started at a median of three and six months by the TimeToStop collaborators and other paediatric epileptologists, respectively. Withdrawal was completed at a median of 12 and 20 months, respectively. For monotherapy, tapering was initiated at five and 11 months in these two groups, and ended at a median of seven and 12 months, respectively. Most TimeToStop collaborators believed that it was not justified to wait 12 months after surgery before reducing AEDs, regardless of the number of AEDs taken. Current AED policies in Europe have changed as a consequence of the retrospective TimeToStop results, and this accounts for why recruitment in a randomised trial was not feasible.