Early 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.

Seizure characteristics and the use of anti-epileptic drugs in children and young people with brain tumours and epileptic seizures: Analysis of regional paediatric cancer service population

PurposeEpileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED). Methodwe undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service. Resultsdata was available on 117/120 (98%) children <18 years: median age at tumour presentation was 8.1 years (IQR 25°−75°: 3.6–12.7), median follow up was 33 months (IQR 25°−75°: 24–56), and 35/117 (29%) experienced seizures.A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9–17.3). At a median follow up of 24 months (IQR25°−75°: 15–48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR25°−75° 5–14 months), and the median follow up after withdrawal was 15 months (IQR25°−75° 5–34 months). ConclusionsSeizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex.The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control.

Seizure characteristics and their treatment in pediatric brain tumour patients: A proposal for a service evaluation criteria

Objective: We aimed to describe the incidence of epileptic seizures in children with brain tumours, risk factors related, the seizure treatments used, the withdrawal of antiepileptic drugs (AEDs). Methods: Case note review of 120 newly diagnosed brain tumour patients referred between 01/2010 and 12/2014 to the regional paediatric cancer service was carried out to determine patient tumour and seizure characteristics, AED treatments and outcomes. Results: We excluded 2 patients because of previous long history of seizure in tuberous sclerosis and 1 patient has been lost in follow up. 67/117 were male (57,3%), median age at tumour presentation was 8.1 years (IQR 25°–75°: 3.6–12.7). The median follow up was 33 months (IQR 25°–75°: 24–56). 29,2% experienced seizures. Risk factors for seizures were cerebral localisation in logistic regression analysis (OR: 7,07 IC 95% 2,89–17,3). In particular, neither age at diagnosis nor tumour type were associated with seizure risk. The epilepsy follow up at a median of 24 months (IQR 25°–75°: 15–48) demonstrated that 37,1% were seizure free (SF) off AEDs, 42,9% were SF on AEDs and 20% experienced refractory epilepsy. The most of them had a single seizure episode (62,9%). 12 patients withdraw AED. The median duration of AED before withdrawal was 11 months (IQR 25°–75°: 5–14 months), and the median follow up after withdrawal was 15 months (IQR 25°–75°: 5–34 months). 4 children had seizure relapse after further acute events (2 had acute hydrocephalus, 1 had sepsis, 1 had ventriculitis after shunt revision). Only 1 patient did not have AED at diagnosis of epilepsy. Conclusion: Epileptic seizures affect about 1/3rd of children presenting with brain tumours, most commonly in cortically-located tumours. The low risk of recurrent seizures after treatment justifies early withdrawal of AED after seizures stabilisation. A 3 month seizure free interval prior to AED withdrawal is proposed for future studies.

Early versus late antiepileptic drug withdrawal for people with epilepsy in remission.

Epilepsy is a chronic neurological disorder which affects millions of people around the world. Antiepileptic drugs (AED) are the main interventions used to prevent seizures and control epilepsy. Although effective in most cases, AEDs are related to long-term adverse effects, such as cognitive and behavioural alterations. Thus when epilepsy is in remission, it may be in the individual's best interest to discontinue medication. However, the optimal timing of AED discontinuation is still unknown.This is an updated version of the original Cochrane review published in Issue 3, 2001. (1) To quantify and compare risk of seizure recurrence, status epilepticus and mortality after early and late AED discontinuation in adult and pediatric epilepsy patients.(2) To assess which variables modify the risk of seizure recurrence.(3) To define a subpopulation in which early AED discontinuation is safe. We searched the Cochrane Epilepsy Group Specialised Register (June 2014); CENTRAL (Issue 5, The Cochrane Library, May 2014); MEDLINE (1946 to June 2014); CINAHL (23 June 2014); Scopus (1823 to June 2014); ClinicalTrials.gov (23 June 2014); and WHO International Clinical Trials Registry Platform (23 June 2014). We also checked the reference lists of studies found through the electronic searches. Randomised controlled trials that evaluate withdrawal of AEDs after varying periods of seizure remission in adults and children with epilepsy. Included studies compared an early AED discontinuation time (defined as a period of remission of seizures of less than two years) versus a late AED discontinuation time (defined as a period of remission of seizures of more than two years). Two authors independently extracted data and assessed trial quality. Risk ratio (RR) with 95% confidence interval (CI) was calculated for each trial. Summary RRs and 95% CIs for dichotomous data were calculated using a fixed-effect model. A test of statistical heterogeneity was conducted for each pooled risk ratio calculation. Each included study underwent a 'Risk of bias' assessment, based on the Cochrane Handbook recommendations, and we examined the overall quality of information through the GRADE system, presented in two 'Summary of Findings' tables. Five trials were included in this review, representing 924 randomised children with epilepsy, all under 16 years of age at randomisation, with a median follow-up of 5.6 years. No eligible trial evaluated adults or assessed mortality or status epilepticus as outcomes. The pooled risk ratio for seizure relapse after AED withdrawal was 1.34 (95% CI 1.13 to 1.59, P = 0.0007). Conforming to this estimate, the number needed to harm, that is expose an individual to a higher risk of seizure relapse because of early withdrawal of AED, is 8 (95% CI 5 to 20). Early discontinuation was associated with greater relapse rates in people with partial seizures with a pooled risk ratio of 1.51 (95% CI 0.97 to 2.35, P = 0.07). Absence type epilepsy showed a lower risk of relapse. Variables associated with higher risk of seizure relapse were abnormal EEG findings (pooled RR 1.44, 95% CI 1.13 to 1.83, P = 0.003), especially epileptiform activity (RR 2.58, 95% CI 2.03 to 3.28, P < 0.0001); epilepsy onset before 2 years or after 10 years of age; history of status epilepticus; intellectual disability (IQ < 70); and high seizure frequency before and during treatment. Gender and family history did not show any significant influence over seizure relapse. Overall, the included trials were classified as low or unclear risk of bias where methodological information was not reported and could not be provided by original study authors. There is evidence to support waiting for at least two seizure-free years before discontinuing AEDs in children, particularly if individuals have an abnormal EEG or partial seizures, or both. There is insufficient evidence to establish when to withdraw AEDs in children with generalised seizures. There is no evidence to guide the timing of withdrawal of AEDs in seizure-free adults. Further high-quality randomised controlled trials are needed, particularly recruiting adults and recruiting those with generalised seizure types, to identify the optimal timing of AED withdrawal and risk factors predictive of relapse.

Timing of antiepileptic drug withdrawal and long-term seizure outcome after paediatric epilepsy surgery (TimeToStop): a retrospective observational study

Postoperative antiepileptic drug (AED) withdrawal practices remain debatable and little is known about the optimum timing. We hypothesised that early AED withdrawal does not affect long-term seizure outcome but allows identification of incomplete surgical success earlier than late withdrawal. We aimed to assess the relation between timing of AED withdrawal and subsequent seizure recurrence and long-term seizure outcome. TimeToStop included patients aged under 18 years from 15 centres in Europe who underwent surgery between Jan 1, 2000, and Oct 1, 2008, had at least 1 year of postoperative follow-up, and who started AED reduction after having reached postoperative seizure freedom. Time intervals from surgery to start of AED reduction (TTR) and complete discontinuation (TTD) were studied in relation to seizure recurrence during or after AED withdrawal, seizure freedom for at least 1 year, and cure (defined as being seizure free and off AEDs for at least 1 year) at latest follow-up. Cox proportional hazards regression models were adjusted for identified predictors of timing intervals. TimeToStop included 766 children. Median TTR and TTD were 12·5 months (95% CI 11·9-13·2) and 28·8 months (27·4-30·2), respectively. 95 children had seizure recurrence during or after AED withdrawal. Shorter time intervals predicted seizure recurrence (hazard ratio [HR] 0·94, 95% CI 0·89-1·00, p=0·05 for TTR; and 0·90, 0·83-0·98, p=0·02 for TTD). After a mean postoperative follow-up of 61·6 months (SD 29·7), 728 patients were seizure free for at least 1 year. TTR and TTD were not related to regain of seizure freedom after restart of drug treatment (HR 0·98, 95% CI 0·92-1·05, p=0·62; and 0·93, 0·83-1·05, p=0·26, respectively), or to seizure freedom (0·97, 0·89-1·07, p=0·55; and 1·03, 0·93-1·14, p=0·55, respectively) or cure (0·97, 0·97-1·03, p=0·84; and 0·98, 0·94-1·02, p=0·31, respectively) at final follow-up. Early AED withdrawal does not affect long-term seizure outcome or cure. It might unmask incomplete surgical success sooner, identifying children who need continuous drug treatment and preventing unnecessary continuation of AEDs in others. A prospective randomised trial is needed to study the possible cognitive effects and confirm the safety of early AED withdrawal after epilepsy surgery in children. Dutch National Epilepsy Fund.

Four-year outcome after early withdrawal of antiepileptic drugs in childhood epilepsy

Four-year follow-up of children with epilepsy included in a randomized trial of early withdrawal of antiepileptic drugs showed that 51% achieved a terminal remission of at least 2 years without medication and 21% with medication; 15% had seizures during the fourth year. Early medication withdrawal is not recommended as standard practice in children with a rapid response to medication. The authors developed a model to predict outcome if withdrawal is considered.

Seizure outcome in patients with a solitary cerebral cysticercus granuloma.

To study the long-term seizure outcome and determine factors that predict recurrence of seizures following early withdrawal of antiepileptic drugs (AEDs) in patients with a solitary cerebral cysticercus granuloma (SCCG). The authors prospectively studied 185 patients with SCCG and seizures in whom AEDs were withdrawn soon after (within 2 to 12 weeks) resolution of the SCCG was demonstrated on the CT scan. The follow-up of these patients ranged from 24 to 125 months (mean 65.8 months) or until seizure recurrence. Age, number of seizures, duration of AED therapy, occurrence of breakthrough seizures, administration of albendazole, and presence of a calcific residue of the SCCG on the CT scan were studied as prognostic factors to predict recurrence of seizures. One hundred fifty-seven patients (84.9%) were seizure-free, whereas 28 patients (15.1%) had recurrence of seizures after withdrawal of AEDs. The recurrences occurred at a mean duration of 18.8 months (range 0.5 to 78 months) after withdrawal of AEDs. Multivariate analysis showed that presence of calcific residue on the CT scan, occurrence of breakthrough seizures, and occurrence of more than two seizures were associated with a higher risk of recurrence of seizures. The other factors including administration of albendazole therapy did not affect seizure recurrence. Nearly 85% of patients with a solitary cerebral cysticercus granuloma have a good seizure outcome following resolution of the lesion and early withdrawal of AEDs. However, recurrence of seizures can be expected in about 15% of patients. Patients with more than two seizures, those with breakthrough seizures, and those whose follow-up CT scan shows a calcific residue of the granuloma have a higher risk of recurrence and therefore need to be appropriately cautioned after withdrawal of AEDs. AED therapy might also have to be continued for longer periods in patients with these risk factors.

Early versus late antiepileptic drug withdrawal for people with epilepsy in remission.

Antiepileptic drugs ( AEDs) are used to prevent seizures but are associated with both short and long term adverse effects. When epilepsy is in remission, it may be in the patient's best interest to discontinue medication. However, the optimal timing of AED discontinuation is not known. To quantify seizure relapse risk after early (less than two seizure free years) versus late (more than two seizure free years) AED withdrawal in adult and pediatric epilepsy patients. To assess which variables modify the risk of seizure recurrence. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled trials register (Cochrane Library Issue 4, 2000), MEDLINE (January 1996 to January 2001), EMBASE, Index Medicus, CINAHL, as well as hand-searching of journals. Randomized controlled trials that evaluate withdrawal of AEDs after varying periods of seizure remission in adult and pediatric epilepsy patients with or without blinding were included. Included studies compared an early versus late AED discontinuation. Two reviewers independently extracted data and assessed trial quality. Relative risks with 95% confidence intervals were calculated for each trial. Summary relative risks and 95% confidence intervals for dichotomous data were calculated using a random effects model. A test of statistical heterogeneity was conducted for each pooled relative risk calculation. Seven eligible controlled trials were included in the analysis representing 924 randomized pediatric patients. There were no eligible trials evaluating adult seizure free patients. The pooled relative risk for seizure relapse in early versus late AED withdrawal was 1.32 (95% confidence interval 1.02 to 1.70). On the basis of this estimate, the number needed to harm, that is expose an individual to a higher risk of seizure relapse because of early withdrawal of AED, is 10. Early discontinuation was associated with greater relapse rates in patients with partial seizures[pooled RR = 1.52; 95% confidence interval 0.95 to 2.41] or an abnormal EEG [pooled RR=1.67; 95% confidence interval 0.93 to 3.00]. There is evidence to support waiting for at least two or more seizure free years before discontinuing AEDs in children, particularly if individuals have an abnormal EEG and partial seizures. There is insufficient evidence to establish when to withdraw AEDs in pediatric patients with generalized seizures. There is no evidence to guide the timing of withdrawal of AEDs in adult seizure free patients. Further blinded randomized controlled trials are needed to identify the optimal timing of AED withdrawal and risk factors predictive of relapse.

Early Withdrawal of Antiepileptic Drugs

Recurrence rate, risk factors for recurrence, and outcome in 161 children after early withdrawal of antiepileptic drugs (AEDs) were studied at Leiden University and other centers in The Netherlands.