Standard Approach to Antiepileptic Drug Treatment in the United Kingdom

Summary: In the United Kingdom, the question of whether to commence antiepileptic drug (AED) treatment remains controversial. Surveys indicate that 15% of patients are treated after a first seizure. Pediatricians often wait for a third or fourth seizure before treating, whereas clinicians who deal with adult patients are more likely to intervene early, largely because of concerns about driving and employment. Monotherapy is becoming the rule for the majority of patients. The four primary AEDs in the United Kingdom are carbamazepine and phenytoin (˜ 30% each), valproate (VPA; ˜25%), and phenobarbital (˜ 18%). For partial epilepsies, studies show few major differences in efficacy among these four AEDs. A first-line AED should be one, such as VPA, with a broad spectrum of activity that is easily managed by clinicians who may not have special expertise in the recognition of differing seizure types and epilepsy syndromes. Where differences in efficacy are marginal, comparative drug toxicity may be a major factor in AED selection. Most new AEDs have low toxicity profiles. With respect to discontinuation, pediatricians usually recommend a trial discontinuation period in most children who achieve a 1- or 2-year remission of epilepsy. For adults, however, overall relapse rates after discontinuation are – 40¹-50%; therefore, patients usually opt for long-term AED therapy.     

Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience

PURPOSE: Although epilepsy surgery, especially temporal lobe epilepsy surgery, is well established to control seizures in patients remaining on antiepileptic drug (AED) treatment, less information is available about how many seizure-free surgical patients will relapse after discontinuation of AEDs under medical supervision. METHODS: A literature review yielded six retrospective clinical observations. RESULTS: After planned discontinuation of AEDs in patients rendered seizure free after epilepsy surgery, most often various forms of temporal lobe surgery, the mean percentage recurrence rate in adults in four studies was 33.8%[95% confidence interval (CI), 32.4-35.2%], with maximum follow-up ranging from 1 to 5 years. Seizure recurrence increased during the follow-up of 1 to 3 years and occurred within 3 years of AED discontinuation. In one study of children with temporal lobe epilepsy, the recurrence rate was 20%. More than 90% of adult patients with seizure recurrence regained seizure control with reinstitution of previous AED therapy. Seizure recurrence was unaffected by the duration of postoperative AED treatment; as a consequence, delaying discontinuation beyond 1 to 2 years of complete postoperative seizure control seems to have no added benefit. The occurrence of rare seizures or auras after surgery did not eliminate the possibility of eventual successful AED discontinuation. CONCLUSIONS: AED discontinuation is associated with a seizure recurrence in one in three patients rendered seizure free by epilepsy surgery. These results will be useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.     

Antiepileptic Drug Therapy: When Is Epilepsy Truly Intractable?

Summary: We define intractable in the first 5 years of epilepsy treatment as an average of at least one seizure every 2 months. For the longer term, we define intractable as at least one seizure per year. Population studies from Chicago, IL, U.S.A., Finland, and Nova Scotia, Canada indicate that with long follow-up, many children with intractable epilepsy eventually have remission of their seizure disorder. Epilepsy is no longer intractable when the seizures stop completely. How often does a new antiepileptic drug (AED) render a child seizure-free when one or more AEDs have failed? Literature on adults with epilepsy suggests that few with chronic epilepsy who have not achieved seizure control with several AEDs will achieve complete seizure control with additional AEDs. The Nova Scotia study suggests that if a child's seizure fails to be controlled with a first AED, there is an increased risk of intractable epilepsy. Nonetheless, the chance of eventual, complete remission of epilepsy (seizure-free without AED treatment) is approximately 40%. We conclude that intractability should not be considered until there has been failure of at least three first-line AEDs. Intractable epilepsy is rare. Careful definition of the characteristics of children with intractable epilepsy who do respond completely to new AEDs will likely provide the only rational approach to treatment of children with three drug failures. Collaboration by multiple epilepsy centers will be required to gain this information.     

Prognosis after late relapse following epilepsy surgery

OBJECTIVES: To assess prognosis after late relapse in patients who are seizure free for the first 5 years after epilepsy surgery. METHODS: Patients who were seizure free for the first 5 years after resective epilepsy surgery were included. Date of first seizure recurrence, current seizure status, medication, age, and type of surgery were prospectively registered. Non-parametric statistics were used. RESULTS: One hundred and fifty-nine patients were studied. Thirty-two had at least one recurrent seizure. Time to event analysis showed an annual relapse rate of 4% between years 5 and 10 after surgery. At study termination, 143 of 159 patients (89.9%) were in terminal remission. For 30 patients with late relapse and at least 1-year follow-up thereafter, 53% were in terminal remission and 30% had experienced only rare or nocturnal seizures. Medication use was not associated either with likelihood of relapse or entering remission after relapse. CONCLUSIONS: Patients who are seizure free for the first 5 years after epilepsy surgery remain at risk for seizure recurrence. These relapses are often isolated events, and the long-term prognosis after relapse is often good. Relapse rates were similar in patients on and off AEDs, but the relation between AED taper and relapse is uncertain since patient groups may not be similar.     

Prognosis of seizure recurrence after stopping antiepileptic drugs in seizure-free patients: A long-term population-based study of childhood-onset epilepsy

The long-term outcome with respect to seizure relapse after planned discontinuation of antiepileptic drugs (AEDs) in seizure-free patients is not well known. Relapse and its treatment outcome were evaluated in a longitudinal population-based study of 148 patients from the onset of their epilepsy to an average follow-up of 37 years. During the study, AEDs were completely discontinued by 90 patients; 58 patients remained on medication. Seizure relapse after AED discontinuation was observed in 33 (37%) of 90 patients at an average follow-up of 32 years. Among 8 of the 33 patients who elected to restart AEDs, 2 achieved 5-year terminal remission (5YTR), but only 10–19 years after restarting treatment. The other 6 patients never achieved 5YTR, and 2 of the 6 never entered a 5-year remission period during follow-up. Factors associated with failure to reach 5YTR after treatment of relapse were symptomatic etiology and localization-related epilepsy. In conclusion, drug discontinuation after seizure freedom results in relapse in one-third of patients. Reinstitution of a medication that worked for years fails to achieve control in one of four patients. These risks need to be considered, although there is no evidence that discontinuation is responsible for the poor prognosis for treatment of seizure recurrence.     

Antiepileptic drug withdrawal after successful surgery for intractable temporal lobe epilepsy

PURPOSE: To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy. METHODS: The clinical courses after temporal lobectomies (TLs) were retrospectively analyzed in 88 consecutive patients. All the patients had TLs as the only surgical procedure, and they had been followed up for longer than 3 years. AED discontinuation was attempted if the patient had been seizure free without aura for >or=1 year during the follow-up period. RESULTS: Sixty-six (75%) patients achieved complete seizure freedom for >or=1 year; 28 patients were seizure free immediately after surgery (immediate success); and 38 patients became seizure free after some period of recurrent seizures (delayed success). AED discontinuation was attempted in 60 (91%) of 66 patients with a successful outcome. In 13 (22%) patients, seizure relapse developed during AED reduction (n=60), and in seven (12%) patients after discontinuation of AEDs (n=38). The seizure recurrence rate was not different between the immediate-and delayed-success groups. Among 20 patients with seizure relapse related to AED tapering, nine (45%) of them regained seizure freedom after reinstitution of AED treatment, and AEDs were eventually discontinued in six of them. Seizures that recurred after complete AED discontinuation had a better prognosis than did the seizures that recurred during AED reduction (seizure freedom in 86% vs. 23%). At the final assessment, 54 (61%) patients had been seizure free >or=1 year; 37 without AEDs and 17 with AEDs. The successful discontinuation of AEDs was more frequent for patients with a younger age at the time of surgery and for those patients with shorter disease duration. CONCLUSIONS: Our results suggest that seizure freedom without aura at >or=1 year is a reasonable indication for the attempt at AED discontinuation. The subsequent control of recurrent seizures was excellent, especially if seizures relapsed after the complete discontinuation of AEDs. Younger age at the time of surgery and a shorter disease duration seem to affect successful AED discontinuation for a long-term period.     

Outcome After Discontinuation of Antiepileptic Drug Therapy in Children with Epilepsy

We studied recurrence risks and predictive factors of relapse after antiepileptic drug (AED) discontinuation in a prospective analysis of 425 children with epilepsy who had not had a seizure for at least 2 years (follow-up after withdrawal 1.6-12 years, mean 8 years). Factors closely related by multivariate analysis to relapse were neurologic abnormalities, mental retardation, seizure type (infantile spasms, absence seizures), and appearance or persistence of EEG abnormalities during the course of the illness and before discontinuation. When multivariate analysis was performed to evaluate outcome of patients with a first relapse (isolated vs. multiple relapses), the variables closely related to a poor prognosis were etiologic factors, first relapse characterized by more than one seizure in a 24-h period, seizure-free period less than 4 years, unchanged seizure type at first relapse, more than one AED for seizure control, and abnormal EEG before the first relapse. In itself, resumption of therapy did not influence outcome. At the study cutoff point, 88% of patients with relapse were again seizure-free. We conclude that AEDs can safely be discontinued if predictive factors are considered to individualize the risk of relapse for each patient.     

Long term course of childhood epilepsy following relapse after antiepileptic drug withdrawal

OBJECTIVE: To explore the course of epilepsy following relapse after antiepileptic drug (AED) withdrawal. METHODS: Forty two patients were identified with onset of epilepsy in childhood in whom AEDs had been withdrawn after at least 2 years of seizure freedom, and in whom a relapse had occurred. Two patients were lost to follow up. RESULTS: Median follow up after AED withdrawal was 5.9 years (range 1.6-13.2 years). Relapse occurred in more than half of the patients within 6 months of AED withdrawal. At the end of follow up, 12 patients (30%) were seizure free for at least 1 year (mean 10.4 years) without medication; 16 (40%) were seizure free for at least 1 year (mean 5.3 years) with ongoing medication; and 12 patients (30%) were seizure free for less than 1 year with medication. No status epilepticus occurred in any patient after withdrawal. Age at onset, if over the age of 5, combined with normal intelligence were predictive of an excellent outcome; presence of a neurological disorder, and hence symptomatic aetiology, was predictive of poor outcome after a relapse. CONCLUSIONS: Fears that premature withdrawal of AEDs might result in uncontrollable seizures were unsubstantiated in this study. The current practice of withdrawing AEDs in children who have been seizure free for 2 years can be beneficial to most of these patients.     

Prognosis after withdrawal of antiepileptic drugs in childhood-onset cryptogenic localization-related epilepsies

The purpose of this study was to clarify the risk factors of relapse following discontinuation of AEDs in patients with childhood-onset cryptogenic localization-related epilepsies. The subjects were 82 patients who fulfilled the following criteria: (1) age at first visit of less than 15 years, (2) follow-up period of more than 5 years, (3) suffering from cryptogenic localization-related epilepsies, and (4) the patient underwent AED withdrawal during the follow-up period. As a basic principle, we decided to start withdrawing AEDs when both of the following two conditions were met: (1) the patient had a seizure-free period of 3 years or more, and (2) there were no epileptic discharges on EEGs just prior to the start of withdrawal. Seizures recurred in eight of the 82 patients (9.8%). Univariate analysis revealed that the following factors were correlated with higher rates of seizure relapse: 6 years of age or higher at onset of epilepsy; 15 years of age or higher at the start of AED withdrawal; 5 years or more from the start of AED treatment to seizure control; five or more seizures before seizure control; and two or more AEDs administered before seizure control. Among these risk factors, 6 years of age or higher at onset and 5 years or more from the start of AED treatment to seizure control were determined by multivariate analysis to be independent risk factors for relapse. Thus, we conclude that the physician should be more careful in discontinuing AEDs in these higher-risk patients groups, and more generous in discontinuing AEDs in lower-risk groups.     

Factors related to successful antiepileptic drug withdrawal after anterior temporal lobectomy for medial temporal lobe epilepsy.

OBJECTIVE: To assess the rate of successful antiepileptic drug (AED) discontinuation, prognostic factors and proper time of AED withdrawal after surgery for medial temporal lobe epilepsy (MTLE). METHODS: We reviewed 171 consecutive patients who underwent resective surgery for MTLE. All patients were followed up for more than two postoperative years. AEDs were slowly tapered with an individualized schedule for each patient. Outcome status was determined from medical records and telephone interviews. RESULTS: 41.2% of patients experienced no seizure recurrence. 34.5% discontinued medication without seizure recurrence for more than 2 years at final assessment. Multivariate analysis revealed that an age greater than 30 years at surgery and postoperative AED reduction before 10 months increased the risk of recurrence [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1-3.9 and HR 2.5, CI 1.1-5.8]. CONCLUSIONS: Resective surgery for MTLE brings seizure remission without AED to one-third of patients. Postoperative AED tapering is recommended after at least 10 months. Younger age at surgery is a good predictive factor of remission after MTLE surgery.     

A Comparison Between One and Three Years of Treatment in Uncomplicated Childhood Epilepsy: A Prospective Study. II. The EEG as Predictor of Outcome After Withdrawal of Treatment

Summary: Purpose : We wished to evaluate the prognostic usefulness of various EEG parameters with respect to remission rates after discontinuation of antiepileptic drug (AED) therapy in children treated for epileptic seizures.
Methods : Two hundred forty-four children with uncomplicated epileptic seizures were randomized to either 1 or 3 years of treatment with AEDs. The treatment was then discontinued in patients who had been seizure-free during the last 6 months of their allotted time of treatment (n = 154). After treatment discontinuation, the children were followed for at least 2 years. EEG recordings were performed before treatment was initiated and at regular intervals during treatment.
Results : The overall relapse rate was 37%. In many children, the amount of epileptiform activity varied considerably between subsequent recordings made during the treatment. The remission rate was slightly higher for children whose last recordings before AED discontinuation were free of epileptiform activity as compared with children in whom such activity was present. However, children who had irregular generalized spike–wave (SW) activity in the recordings made before discontinuation of treatment had a clearly higher relapse rate (67%) both as compared with children without epileptiform activity (33%) and as compared with children with other types of epileptiform activity (33%) in their last EEG recordings before discontinuation. All children treated for only 1 year whose final EEGs displayed generalized irregular SW activity relapsed.
Conclusions : We conglude that the presence of epileptiform activity does not in itself necessarily influence prognosis after discontinuation of treatment but that certain types of such activity signal a high risk of relapse.     

Prognostic Significance of Failure of the Initial Antiepileptic Drug in Children with Absence Epilepsy

PURPOSE: In children with childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE), to determine the impact of failure of initial antiepileptic drug (AED) for lack of efficacy in eventual seizure control and long-term remission of epilepsy. METHODS: Centralized EEG records for the province of Nova Scotia allowed identification of all children seen with CAE or JAE between 1977 and 1985. Information regarding success or failure of initial AED in fully controlling seizures and long-term seizure control and remission of epilepsy was collected by patient questionnaire and chart review. RESULTS: Eighty-six of 92 eligible patients were followed up (75 CAE, 11 JAE). Initial AED treatment was successful in 52 (60%) of 86. Success tended to be greater for valproate (VPA) than for other AEDs (p = 0.07), and lower if generalized tonic-clonic or myoclonic seizures coexisted (p < 0.004 and p < 0.03). Terminal remission was more likely if the initial AED was successful than if it had failed (69% vs. 41%; p < 0.02). Compared with those in whom the initial AED was successful, subjects whose initial AED had failed were more likely to progress to juvenile myoclonic epilepsy (JME) at last follow-up (32% vs. 10%; p < 0.02) and to develop intractable epilepsy (17% vs. 2%; p < 0.04). CONCLUSIONS: Initial AED was successful in 60% of children with AE. If the first AED failed, the outcome was less favorable, with a lower rate of terminal remission and a higher rate of progression to JME and intractable epilepsy.     

Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy

OBJECTIVES: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. METHODS: 330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables. RESULTS: The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings. CONCLUSIONS: Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors.     

Relapse of seizure after withdrawal of antiepileptic drug treatment in childhood epilepsy: age-dependent factors

In 556 epileptic children, clinical and encephalographic factors concerning the discontinuation of antiepileptic drugs (AED) were studied, with emphasis on age-related factors. Seizures relapsed in 80 patients (14.4%), the incidence being high in idiopathic generalized epilepsy with onsets in adolescence or adulthood (juvenile absence epilepsy, juvenile myoclonic epilepsy, grand mal on awakening), symptomatic partial epilepsy and symptomatic generalized epilepsy. The age distribution at the relapse showed two peaks; 9 to 11 and 17 to 19 years. The first peak represented patients with school-age onset epilepsies, and the second those with the adolescent or adult onset epilepsies. The age at discontinuation of AED depended on each epileptic syndrome, and the relapse rate was significantly higher when the AED was discontinued after adolescence. In 56 patients, seizure relapsed during the withdrawal phase or less than 1 year after the discontinuation. The type of the relapsing seizure was the same as the previous ones. On the other hand, in 16 out of 24 patients whose relapse occurred 1 year or more after the discontinuation, the seizure type was different from the previous ones. These results suggest the relevance of age-dependent factors to the discontinuation of therapy.     

Clinical Science

Anne T. Berg , Barbara G. Vickrey , John T. Langfitt , Michael R. Sperling , Shlomo Shinnar , Carl Bazil , Thaddeus Walczak , and Susan S. Spencer for the Multicenter Study of Epilepsy Surgery
Little evidence guides practice regarding the reduction of AEDs in individuals who achieve significant periods of seizure remission after resective surgery. We assessed the effect of reducing AEDs on relapse in postsurgical patients who achieved at least a 1-year seizure-free remission. We also examined potential predictors of relapse after AED reduction.
Of 396 study subjects, 301 attained a 1-year seizure remission after surgery; 129 reduced AEDs after achieving remission, and 162 did not reduce drugs. Ten patients who stopped all AEDs before attaining remission were excluded from analysis. In all, 114 (39%) patients relapsed: 73 (45%) of 162 in the nonreduction group and 41 (32%) of 129 in the reduction group (p = 0.02). Compared with patients who did not reduce AEDs, patients who reduced drugs were more likely to have remitted immediately after hospital discharge (p < 0.0001). After adjustment for this factor, little or no apparent impact of drug reduction on the rate of relapse was seen. Within the 129 patients who reduced AEDs, only delayed remission after hospital discharge was significantly associated with an increased rate of relapse (RR, 2.26; 95% CI, 1.15–4.48; p = 0.02). Continued auras were marginally associated with relapse (RR, 2.06; p = 0.07).
Although many relapses in this cohort of postsurgical patients who achieved remission occurred in the context of reducing or completely eliminating AEDs, the risk was no higher than that in those who continued AEDs. Randomized studies are needed to test the impact of drug reduction in seizure-free postsurgical patients.     

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.     

Efficacy of New Antiepileptic Drugs

Regarding efficacy of new antiepileptic drugs (AEDs) for seizure control, there are three important clinical questions. How effective are new AEDs when corrected for the efficacy of placebo? And even more important: How do new AEDs fare in terms of seizure remission compared with established agents? And finally: Have patients seizure-free on new AEDs a better chance for lasting remission after withdrawal versus those withdrawing from older agents? The answers raise concerns. Although add-on therapy with marketed new AEDs is more effective than placebo, as expected, the treatment difference for becoming seizure-free is disappointingly small (6%; 95% CI: 4–8%; z = 6.47; p < 0.001). Although many, but not all, new AEDs have comparable efficacy to old standard drugs in well-controlled trials, none of the new AEDs is superior to old drugs in terms of seizure remission. So far, we have no antiepileptogenic treatments that prevent the development of epilepsy or modify its detrimental course. The sobering results suggest the need for novel experimental and clinical strategies for the development of more effective new AEDs that interrupt ictogenesis more effectively and prevent or abort epileptogenesis. Ideally, we need new drugs that block both ictogenesis and epileptogenesis, resulting in complete cure of epilepsy.Although a large number of new antiepileptic drugs (AEDs) that suppress or prevent seizures are now available, about 30 to 40 percent of the patients, children as well as adults, remain resistant to drug treatment (1). The situation is even worse for a range of severe epilepsy syndromes of infancy and adolescence. So far, we have no antiepileptogenic treatments that prevent the development of epilepsy or modify its detrimental course (2). The introduction of each new AED into the market raises valid expectations in patients and physicians for more effective treatment of epilepsy. Although safety, tolerability, and lack of interactions are important, better efficacy is a crucial feature for a new AED. This brief review is limited to a discussion of the efficacy of new versus old AEDs. In that respect, three questions are of particular clinical interest: How effective are new AEDs when corrected for the efficacy of placebo? And even more relevant: Are new AEDs more often leading to seizure remission compared with established agents? And finally: Can more patients maintain seizure remission after withdrawal of new AEDs compared with withdrawal of older agents? The following brief overview, which is not a comprehensive literature review, outlines the available evidence on the efficacy of modern AEDs based on randomized controlled trials of marketed modern AEDs.     

Antiepileptic Drug-Related Cognitive Complaints in Seizure-Free Children with Epilepsy Before and After Drug Discontinuation

Summary: The cognitive complaints reported by children and their parents, as subjectively associated with antiepileptic drug (AED) treatment, were evaluated in seizure-free children before and after drug discontinuation. The aim of the design was to isolate the cognitive side effects of AEDs from other factors, such as the effect of seizures. Our inventory explored the following areas: "alertness,""concentration,""activation/ tiredness,""memory,""drowsiness,""depression,""aggressiveness," and "hyperactivity," using a 5-point Likert scaling procedure. One hundred two eligible patients were selected, each matched with a healthy control and assessed when still on antiepileptic medication. All children were seizure free for at least 1 year. The medication was then discontinued gradually over a 3-month period. Four months after the children were completely medication free, a second assessment was carried out, but only in the 83 children who remained seizure free and in their matched controls.
The results of the reports made by the children themselves did not show differences with the matched controls, and only showed improvement after drug discontinuation for complaints about "tiredness." Parents of the children with epilepsy reported significant improvement in all areas related to "alertness and activation" after discontinuation of the drugs.
The finding that only a limited number of children have cognitive complaints, both when still on AEDs and after discontinuation, may be in line with the reports that the major factor contributing to quality of life is whether patients are seizure free or still have seizures. All patients in this study were seizure free for a period >1 year, which may have caused the favorable pattern of response in our patient group.     

Reduction of AEDs in postsurgical patients who attain remission

PURPOSE: Little evidence guides practice regarding the reduction of antiepileptic drugs (AEDs) in individuals who achieve significant periods of remission after resective surgery. METHODS: In a prospective study of 396 individuals who underwent resective surgery for intractable seizures, the impact of reducing AEDs on relapse and predictors of relapse were examined. RESULTS: Of 301 study subjects who attained a 1-year seizure remission after surgery, 129 reduced from two to one or from one to no AEDs after achieving remission, and 162 did not reduce drugs. Ten patients who stopped all AEDs before attaining remission were excluded from analysis. In all, 114 (39%) patients relapsed: 73 (45%) of 162 in the nonreduction group and 41 (32%) of 129 in the reduction group (p = 0.02). Patients who reduced drugs were more likely to have remitted immediately after hospital discharge (p<0.0001). After adjustment for this factor, little or no apparent impact of drug reduction on the rate of relapse was noted [rate ratio (RR), 1.1; 95% CI, 0.72-1.71; p=0.64 for reducing from two to one AED, and RR, 0.85; 95% CI, 0.50-1.45; p=0.56 for reducing from one to no AEDs]. Within the 129 patients who reduced AEDs, only delayed remission after hospital discharge was significantly associated with an increased rate of relapse (RR, 2.26; 95% CI, 1.15- 4.48; p=0.02). Continued auras had a marginally significant association with relapse (RR, 2.06; p=0.07) CONCLUSIONS: Although many relapses in this cohort of postsurgical patients who achieved remission occurred in the context of reducing or completely eliminating AEDs, the risk was no higher than in those who continued AEDs. Randomized studies are needed to test the impact of drug reduction in seizure-free postsurgical patients.