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.     

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.     

Prospective study on the withdrawal and reinstitution of antiepileptic drugs among seizure-free patients in west China

This study explored the relapse rates and risk factors for seizure recurrence after discontinuing antiepileptic drug (AED) therapy among seizure-free patients in west China, and explored whether to reinstitute AED immediately after a single seizure after AED withdrawal. Patients with epilepsy who were seizure-free for at least 2 years and decided to gradually stop AED therapy were followed up every 3 months for seizure relapse. Patients who experienced their first seizure after drug withdrawal were divided into two groups according to their willingness to reinstitute AED therapy, and were followed up until their second seizure. In the mean 29.35 months of follow-up, 37 patients (37/162, 22.8%) suffered at least one seizure after withdrawal. The cumulative probability of seizure recurrence was 16% at 12 months and 20.2% at 24 months. AED response time >1 year and multiple types of seizure were identified as risk factors for seizure recurrence. Eight patients (8/32, 25%) suffered a second seizure within 1 year after the first whether or not they reinstituted AED immediately. There were no significant demographic or clinical differences between patients who reinstituted AED therapy and those who did not. The epilepsy recurrence rate after AED withdrawal is relatively low, with a relatively slow tapering process. Patients with long AED response times and/or multiple types of seizures have a higher risk of seizure recurrence. The first seizure after drug withdrawal is not an indication for immediate AED reinstitution, but may be recommended after a second seizure.     

Seizure recurrence and risk factors after antiepilepsy drug withdrawal in children with brain tumors

Summary:  Purpose: To study seizure outcome after antiepilepsy drug (AED) withdrawal in brain tumor patients and to analyze risk factors for seizure recurrence.
Methods: Brain tumor patients with seizures and at least one attempt at AED discontinuation were identified from the hospital database and neurology clinic records. After defining study variables, patient charts were abstracted for clinical and demographic data. Statistical analyses used log-rank tests and multivariable Cox proportional hazards models.
Results: Sixty-two patients discontinued AEDs at a median time of 5.6 years from the first seizure (range, 1.2–19.6 years). Median time since AED withdrawal was 2.3 years (range, 0.4–15.1 years). Seizures recurred in 17 (27%) patients within a median time of 0.8 years (range, 0.06–7.7 years). Median seizure-free period before AED withdrawal was 1.3 years (range, 0.1–11 years). More than one tumor resection and whole-brain radiation treatment (WBRT) were associated with seizure recurrence, whereas posterior fossa tumor location was correlated with reduced seizure recurrence risk. At seizure recurrence, control was easily reestablished in 10 patients with AED reinstitution and after dose adjustment in five; two patients with poor drug compliance continue to have seizures. In 48 patients who had an EEG before AED withdrawal, spikes or slow waves did not correlate with seizure recurrence.
Conclusions: AED withdrawal can be successfully achieved in majority of carefully selected patients. WBRT and multiple tumor resections seem to be associated with an increased hazard for seizure recurrence.     

Early antiepileptic drug reduction following anterior temporal lobectomy for medically intractable complex partial epilepsy.

PURPOSE: To determine the safety, in our practice, of allowing patient preference to influence the timing of antiepileptic drug (AED) reduction, once they became seizure-free after anterior temporal lobectomy (ATL). METHODS: Thirty patients underwent anterior temporal lobectomy for medically intractable complex partial epilepsy at Loma Linda University Medical Center between December 1st 1991 and November 30th 2001. Timing of AED reduction in seizure-free patients was based on patient request. A review of patient records noted seizure status, duration from surgery to AED reduction, AED side effects, seizure recurrence and whether control was regained. RESULTS: Twenty-four (80%) of the 30 patients became seizure-free on their preoperative AEDs after initial ATL; three additional patients after a second operation. AEDs were not reduced in the reoperated patients, the three patients who did not become seizure-free, and in two patients who asked to increase AEDs to control auras. Thus, AEDs were reduced in 22 of the 27 seizure-free patients. Patients were followed an average of 3.4 +/- 2.7 (mean +/- standard deviation) years. AED reduction was initiated 4.6 +/- 7.2 months (range 0-27 months) after surgery. Polytherapy use decreased from 54% preoperatively to 18% at last follow up. Seizures recurred in six patients (27% of 22); three became seizure-free after AED adjustments. CONCLUSIONS: In our practice, using an individualized approach to AED reduction following successful epilepsy surgery resulted in early reduction in AEDs. Our data suggest that early AED reduction can be performed safely and without undue risk of seizure recurrence.     

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.     

How effective is surgery to cure seizures in drug-resistant temporal lobe epilepsy?

It is well recognized that two-thirds of patients with drug-resistant temporal lobe epilepsy will be free of disabling seizures with continued medical treatment after temporal resection. Seizure recurrence has been noted during a five-year follow-up in approximately one-third of these seizure-free patients mostly but not exclusively following planned complete discontinuation of antiepileptic drugs (AEDs). This leaves one-third of patients without disabling seizures and without AEDs several years after surgery. Despite improvements in seizure frequency or severity, seizures persist in another third of patients undergoing surgery. Although cure (five years without any seizures and off AEDs) is the ultimate aim of epilepsy surgery, the percentage of patients cured by surgery cannot be well defined at the moment. We need a long-term randomized controlled trial on AED discontinuation in seizure-free patients followed by long-term open extension to determine if only one in three adult patients with drug-resistant temporal lobe epilepsy is cured by surgical intervention.     

Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: a review of current clinical experience

PURPOSE: We reviewed the impact of planned discontinuation of antiepileptic drugs (AEDs) in seizure-free patients on seizure recurrence and the seizure outcome of reinstituted treatment. METHODS: A literature review was performed yielding 14 clinical observations of seizure recurrence after discontinuation and its treatment outcome. RESULTS: Seizure recurrence rate after AED discontinuation ranged between 12 and 66% (mean 34%, 95%CI: 27-43) in the 13 reviewed studies (no data in one study). Reinstitution of AEDs after recurrence was efficacious between 64-91% (mean of 14 studies, 80%, 95%CI: 75-85%) at follow-up. Mean follow-up ranged from 1-9 years. Seizure outcome of resumed treatment was not different for series in children and adolescents (84%, mean of 4 studies, 95%CI: 75-93) or in adults only (80%, mean of 9 studies, 95%CI: 74-86). Although seizure control was regained within approximately one year in half of the cases becoming seizure free, it took some patients as many as 5-12 years. In addition, in 19% (mean of 14 studies, 95%CI: 15-24%), resuming medication did not control the epilepsy as before, and chronic drug-resistant epilepsy with many seizures over as many as five years was seen in up to 23% of patients with a recurrence. Factors associated with poor treatment outcome of treating recurrences were symptomatic etiology, partial epilepsy and cognitive deficits. CONCLUSIONS: These serious and substantial risks weigh against discontinuation of AEDs in seizure-free patients, except perhaps for selected patients with idiopathic epilepsy syndromes of childhood or patients with rare seizures.     

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.     

Seizure freedom off antiepileptic drugs after temporal lobe epilepsy surgery.

Data are limited on seizure recurrence after antiepileptic drug (AED) discontinuation in operated seizure-free patients. We reviewed seizure outcome in patients who came off AEDs after being seizure-free for 2 years following temporal lobe surgery in our center. Thirty-nine (68%) of 57 patients who discontinued AED therapy remained seizure-free. They had a younger age at surgery than the group with seizure recurrence (p=0.01). Earlier surgery may be a favorable predictor for seizure freedom after AED discontinuation.     

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.     

Withdrawal of antiepileptic drugs in adult patients free of seizures for 4 years: a prospective study

We aimed to assess the relapse rate of epilepsy, prospectively attributable to antiepileptic drug (AED) withdrawal in seizure-free patients and to determine the risk factors for seizure recurrence. Seventy-nine patients with epilepsy who were seizure-free for at least 4 years were enrolled into the study. The AEDs were tapered by one-sixth every 2 months. The EEG and clinical examination were performed at the beginning; at each visit during discontinuation and 2, 6, 12, 24, and 36 months after the complete drug withdrawal. For each patient, records were obtained of the main demographic and clinical variables. A total of 49 patients completed the discontinuation programme. Twenty-eight patients (57%) relapsed while 21 of those (42.8%) did not suffer a relapse at the end of the study period. In patients discontinuing treatment, the probability of relapse was 21.4% during the tapering period (especially in the last months), 28.6% at 1 month, 14.3% at 3 months, 3.6% at 6 months, 7.1% at 12 months, 17.8% at 24 months, and 7.1% at 36 months. The age at onset of epilepsy and the duration of active disease were found to affect the risk of relapse. Although drug withdrawal could be considered in adult patients free of seizures for 4 years, the final decision should be tailored to the patient's clinical, emotional, and socio-cultural profile.     

Failed surgery for temporal lobe epilepsy: predictors of long-term seizure-free course

OBJECTIVES: To identify prognostic factors which predict the outcome 2 years after TLE surgery in those patients who were not seizure-free at the 6-month postoperative examination. METHODS: We included 86 postoperative TLE patients who had undergone presurgical evaluation, including video-EEG and high-resolution MRI, and who had seizures between the second and sixth postoperative months. RESULTS: 32% of patients were seizure-free in the second postoperative year. We found that normal MRI findings and secondarily generalized seizures (SGTCS) preoperatively were associated with a non-seizure-free outcome, while rare postoperative seizures and ipsilateral temporal IED with seizure-free outcome. Newly administered levetiracetam showed a significant positive effect on the postoperative outcome independent of other prognostic factors. Five of seven patients who received levetiracetam became seizure-free (p = 0.006). CONCLUSION: One-third of patients who did not become seizure-free immediately after surgery, eventually achieved long-term seizure freedom. We suggest watching for long-term seizure freedom after failed epilepsy surgery especially in patients who had rare postoperative seizures, focal MRI abnormality, ipsilateral temporal spikes, or no SGTCS preoperatively. Levetiracetam may have a positive effect on postsurgical seizures.     

Late seizures in patients initially seizure free after epilepsy surgery

PURPOSE: Surgery for medically intractable epilepsy is currently the most effective means of achieving seizure control. Although relatively few long-term outcome studies have been performed, evidence is mounting that the possibility of late seizure recurrence exists, even after an early seizure-free period. No published reports document the rate and predictors of late recurrence in a large series of patients undergoing surgery in the magnetic resonance imaging (MRI) era. METHODS: We retrospectively queried the databases of two epilepsy surgery centers. Patients eligible for study had preoperative MRI scans, were seizure free for 1 year after surgery, and had a minimal follow-up period of 3 years. Patients with tumors or vascular lesions were excluded. We performed log-rank comparison of Kaplan-Meier product limit estimates for categoric variables and used a Cox proportional hazards model for continuous variables. Variables that were significant (p<0.05) on a univariate screen were entered into a multivariate forward step-wise Cox regression. RESULTS: The study included 285 patients, 254 with medial temporal lobe (MTLE) and 31 with neocortical epilepsy. The probability of having a single seizure after being seizure free for 1 year was 18.3% at 5 years and 32.7% at 10 years. However, only 13% were not seizure free at the last follow-up. Predictors of late recurrences on both uni- and multivariate analysis were the presence of preoperative generalized tonic-clonic (GTC) seizures in patients with neocortical epilepsy and late age at surgery in patients with MTLE. MRI results and location of surgery were not predictive. CONCLUSIONS: Although the risk of at least one recurrent seizure after initially successful epilepsy surgery is relatively high, the rate of recurrent intractability is low. The finding that late age at surgery and presence of preoperative GTC seizures are predictors of late recurrence indicates the importance of patient selection and early surgery for persistent seizure control.     

癫痫无发作患者撤药后的长期结局及复发的危险因素分析

目的 探讨癫痫无发作患者撤药后的长期结局及影响复发的危险因素。方法 本研究包含141例至少3年无发作的癫痫患者,自撤药开始随访至少3年或直到癫痫复发; 根据是否复发分为无发作组和复发组; 对连续变量和分类变量分别采用t检验和卡方检验。用多元回归分析复发危险因素。Kaplan-Meier生存曲线用来计算累积复发率。结果 141例患者中63例(44.7%)复发,78例(55.3%)在随访结束时仍无发作。平均复发时间是撤药后14个月,大多数复发在24个月内(81.0%); 撤药后的累积复发率在第6、12、24、36、48、60个月分别为19.1%、29.8%、36.2%、42.6%、43.4%、43.4%。单因素分析显示早期3个月内药物未控制发作组复发率高于早期3个月内药物控制发作组; 围产期损伤组复发率高于无围产期损伤组、需多药控制者组复发率高于单药控制组。进一步多因素回归分析发现有围产期损伤[风险比(HR)=5.000,95%置信区间(CI)=1.428～17.544]和需多药控制(HR=3.509,95% CI=1.545～8.000)是复发的独立危险因素。结论 癫痫复发主要发生在开始撤药后的前24个月,撤药后3年的无发作保留率为57.4%。撤药后复发的独立危险因素是有围产期损伤史和需多药控制。     

Outcomes After Seizure Recurrence in People with Well-Controlled Epilepsy and the Factors That Influence It

Summary: Purpose: To determine the risk of further seizures and probability of further remission after a first seizure recurrence in patients in remission of their epilepsy, and to examine the prognostic factors influencing this risk.
Methods: Continued follow-up of a cohort of 409 patients with a recurrence of seizures after randomization to the Medical Research Council (MRC) Antiepileptic Drug Withdrawal Study.
Results: By 3 years after a seizure, 95% of patients have experienced a further 1-year remission of their epilepsy and by 5 years 90% of patients have experienced a further 2-year remission. The most important factors contributing to the risk of further seizures after a first seizure after randomization were the previous seizure-free interval, having partial seizures at recurrence, and having previously experienced seizures while receiving treatment. There was no evidence that the group of patients who had discontinued or reduced treatment before the occurrence of their first seizure after randomization had a different outcome from those patients who continued treatment.
Conclusion: Our results provide no evidence that discontinuation of antiepileptic drugs (AEDs) modifies the long-term prognosis of a person's epilepsy, although it does increase the risk of seizures in the 1- to 2-year period after discontinuation.     

AED discontinuation may be dangerous for seizure-free patients

Despite its benefits, stopping antiepileptic drugs (AEDs) in seizure-free patients is associated with several risks. AED discontinuation doubles the risk of seizure recurrence for up to 2 years compared with continued treatment. On average, one in three patients has a seizure recurrence, though the range can go up to 66% (34%, range 12–66%, 95% CI: 27–43). Furthermore, the outcome of treating a seizure recurrence in patients who have been seizure-free for years is surprisingly poor in some patients. Although the long-term prognosis is not worsened by drug discontinuation, one in five patients does not re-enter remission and for some patients, it may take several years to become seizure-free again. The risk of seizure recurrence is particularly high for those with juvenile myoclonic epilepsy and symptomatic focal epilepsy, the most frequent epilepsies in adults. Seizure-recurrence may have devastating, medical, psychological and social consequences for the individual, for example injury, loss of self-esteem, unemployment and losing a driver’s license. Discontinuation should be avoided in patients with a high risk of seizure recurrence. Given these risks, patients will ultimately have to decide themselves whether they wish to discontinue drug treatment after full informed consent.     

The impact of temporal lobe surgery on cure and mortality of drug-resistant epilepsy: summary of a workshop

The Third International Spring Epilepsy Research Conference took place in Georgetown, Cayman Islands from April 26 to May 3, 2003. One workshop discussed the impact of epilepsy surgery on seizure outcome and mortality of antiepileptic drug (AED)-resistant temporal lobe epilepsy. This article summarizes the information presented at this workshop. Although two-thirds of adult patients undergoing epilepsy surgery become seizure-free with continued AED treatment, current clinical experience shows that seizure recurrence occurs in one-third of patients when AEDs are withdrawn under medical supervision. Additional seizure recurrence occurring after AED taper, poor drug compliance and even while patients continue on AEDs after surgery leave only approximately one-third of patients cured after temporal lobe resection. Mostly because so many patients prefer to stay on AEDs although they are free of disabling seizures after surgery, a randomised controlled trial of AED discontinuation is needed to determine if in fact only one-third of patients are cured after surgery. Based on the functional anatomy of temporal lobe surgery two hypotheses are presented why only a minority of patients are cured after surgery. The type and the prognostic significance of seizures after surgery is discussed. Recent studies have suggested that successful temporal lobe surgery may be able to normalize the increased standard mortality ratio (SMR) of drug-resistant temporal lobe epilepsy. However, pre-existing differences in SMR between those cured and those not cured by temporal lobe surgery and other unresolved methodological issues make it difficult at present to fully evaluate the impact of surgery on mortality. Future studies are thus warranted to specifically address the impact of temporal lobe surgery on cure and mortality.     

The prognostic value of long-term ambulatory electroencephalography in antiepileptic drug reduction in adults with learning disability and epilepsy in long-term remission

We determined the additional yield of ambulatory over routine electroencephalography recordings in predicting seizure recurrence after antiepileptic drug (AED) withdrawal in 15 adult patients with various epilepsy syndromes who had been seizure free for at least 3 years (median=10 years). Eleven of 15 patients (74%) relapsed during or after AED withdrawal. All six patients with epileptiform discharges on ambulatory electroencephalography prior to AED withdrawal relapsed, compared with five of nine patients without epileptiform discharges. Ambulatory electroencephalography significantly increases the yield in detecting epileptiform discharges (n=6) compared with routine electroencephalography (n=1). A negative electroencephalographic finding is only a poor predictor of seizure freedom following AED withdrawal. On clinical grounds, our data suggest that patients with epilepsy, learning disability, and other known risk factors (history of abnormal EEGs and frequent seizures, abnormal MRI) are at great risk of seizure relapse during AED taper, irrespective of very long periods of seizure freedom.     

Lateralization of Event-Related Potentials During Discontinuation of Antiepileptic Medication

Summary: The effect of short-term withdrawal of antiepileptic drugs (AEDs) on auditory event-related potentials (ERPs) was studied in 16 patients undergoing preoperative evaluation for epilepsy surgery. ERPs were performed for all patients during treatment with full medication and after a l-week period during ongoing tapering of AEDs. To clarify whether AED discontinuation would provide evidence of lateralizing for ERPs, we also studied the subgroup of 9 patients who had already undergone temporal lobectomies (TLE group). In the TLE group, if habitual seizures occurred <30 h before the ERP recording session, auditory N1 and P3 amplitudes across sphenoidal electrodes were markedly decreased on the side ipsilateral to the epileptic focus. If seizures did not occur, asymmetries in amplitudes were equivocal and not of lateralizing value. In the whole group, midline N1 latencies for standard responses decreased significantly during AED discontinuation. At baseline, long-term habituation of the N1 component for standard responses was attenuated as compared with that of controls. During AED discontinuation, however, enhanced habituation of N1 was observed in TLE patients who did not exhibit seizures before ERP recording.