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.     

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.     

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.     

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.     

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.     

How safe is it to withdraw antiepileptic drugs following successful surgery for mesial temporal lobe epilepsy?

Purpose: To investigate the feasibility of antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) and to identify the predictors of post withdrawal seizure recurrence. Methods: We prospectively studied the seizure outcome of 310 consecutive patients, who were followed for a minimum of 5 years following ATL for medically refractory mesial temporal lobe epilepsy. In seizure‐free patients, we started AED tapering at 3 months in patients on duotherapy/polytherapy and at 1 year after ATL for those on monotherapy. We used Kaplan‐Meier survival curves to estimate the probability of seizure recurrence and complete AED discontinuation, and compared the attributes of recurred and nonrecurred groups of patients by univariate and multivariate logistic regression analyses. Key Findings: Immediately after ATL, 197 patients were on duotherapy and 101 were on monotherapy. We attempted AED withdrawal in 258 patients (83.2%). Sixty‐four patients (24.8%) had seizure recurrence while reducing AEDs. Of 26 patients who had seizure recurrence after complete AED withdrawal, 24 (92.3%) again became seizure‐free after restarting the AEDs. Absence of hippocampal sclerosis on pathologic examination and abnormal postoperative electroencephalogram (EEG) predicted seizure recurrence on multivariate analysis. At the end of follow‐up duration of 8.0 ± 2.0 years, 163 patients (52.6%) were AED free. The cumulative probability of achieving AED‐free status among patients in whom AED withdrawal was attempted, was 44% at fourth year, 65% at sixth year, 71% at eighth year, and 77% at 10th year after ATL. Significance: AED withdrawal can be safely attempted following successful ATL. Seizure recurrences are few and can be managed easily.     

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.     

Kaplan-Meier analysis on seizure outcome after epilepsy surgery: do gender and race influence it?

OBJECTIVE: To evaluate seizure outcome following epilepsy surgery for patients with temporal lobe epilepsy and evaluate is gender and race/ethnicity influence it. METHODS: Data were obtained from the discharge database of the University of Alabama at Birmingham, Epilepsy Center, between 1985 and 2001. The sample consisted of all patients with a primary diagnosis of medically intractable temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy. Seizure recurrence was tabulated at 7 days, 2 months, 6 months, 1, 2, 3, 4, 5, and 6 years following surgery. Logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for all patients. Kaplan-Meier analysis was done to obtain estimates and 95% CIs of seizure freedom from baseline. Baseline variables--age at surgery, age at seizure onset, sex, side of resection, immediate postoperative seizures, and pathology results--were assessed as potential predictors of each outcome by comparing the survival curves within each variable with a log rank test. RESULTS: Three hundred sixty-eight patients underwent surgical treatment for TLE, mean age of 30.2 years. Thirty-five patients were African American, 43% were men. Immediate postoperative seizures were seen in 23 patients, while seizure recurrence occurred in 27.3% patients within a year after surgery, and in 33.6% within 6 years. Logistic regression results showed no differences between African Americans and whites, between males and females. The occurrence of immediate postoperative seizures was a strong predictor of late seizure recurrence only at 1 year after surgery. CONCLUSIONS: The occurrence of seizures in the immediate postoperative period is a strong predictor of later seizure recurrence. Sex and race/ethnicity do not appear to be predictors of long-term outcome following surgery for temporal lobe epilepsy.     

Levetiracetam may favorably affect seizure outcome after temporal lobectomy

Purpose: To study the prognostic implications of antiepileptic drug (AED) use on seizure freedom following temporal lobe resections for intractable epilepsy. Methods: Seizure outcome implications of epilepsy characteristics and AED use were studied in patients who underwent temporal lobectomy patients at the Cleveland Clinic between September 1995 and December 2006. Survival analysis and multivariate regression with Cox proportional hazard modeling were used. Complete seizure freedom was defined as a favorable outcome. Key Findings: Records of 312 patients were analyzed (mean ± standard deviation follow‐up 3.5 ± 1.7 years). The estimated probability of complete seizure freedom was 69% at 12 months (95% confidence interval [CI] 66–72%), and 48% at 36 months (95% CI 45–52%). The mean number of AEDs used per patient at the time of surgery was 1.78 (range 1–4), dropping to 1.02 at last follow‐up (range 0–4). Following multivariate analysis, a lower preoperative seizure frequency and perioperative use of levetiracetam predicted a favorable outcome (risk ratio [RR] 0.62, 95% CI 0.43–0.89, and RR = 0.57, 95% CI 0.39–0.83, respectively), whereas nonspecific pathology (RR 1.71, 95% CI 1.15–2.47) and a higher number of AEDs used at the time of surgery correlated with higher rates of seizure recurrence (whole‐model log‐rank test p‐value < 0.0001). Better outcomes within the levetiracetam group were seen despite a higher proportion of several poor prognostic indicators within this patient group, and started as early as 4 months after surgery, gradually increasing to a 15–20% survival advantage by 5 years. No similar outcome correlations were identified with another AED. Significance: AED use may be a potential new modifiable seizure‐outcome predictor after temporal lobectomy. This possible prognostic indicator is discussed in light of proposed seizure recurrence mechanisms.     

Limitations in the Medical Treatment of Cryptogenic or Symptomatic Localization-Related Epilepsies of Childhood Onset

Summary: We retrospectively examined 169 patients who had cryptogenic or symptomatic localization-related epilepsies (LRE) and were followed-up for more than 5 years. The probability of seizure control was 0.13 during the first year of treatment, 0.25 during the first 5 years, and 0.09 during the second and third 5 years. No patients who continued to have intractable seizures for 15 years became free of seizures. The onset of LRE at the age of 3 years or less, seizure cluster, mesial temporal sclerosis (MTS), and temporal lobe epilepsy (TLE) were significantly associated with a poor seizure control. If an antiepileptic drug (AED) failed to control seizures, probability of seizure control by the next drug was low, in particular in patients in whom more than 4 AEDs have already been tried, and seizure control could not be expected after a trial of 6 AEDs. A tentative indication of epilepsy surgery for LRE of childhood onset may be 5 years of poor seizure control and/or failure of four AEDs.     

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.     

Tuesday July 4, 200615:00–17:00Hall 5ADiscussion Group SessionThe spectrum of temporal "plus" epilepsy

¹ D. Schmidt (   ¹ Epilepsy Research Group, Berlin, Germany )
Temporal lobe surgery is the nonpharmacological treatment of choice for carefully selected patients with drug resistant temporal lobe epilepsy. On average, two of three patients undergoing surgery will become seizure free or nearly seizure free after surgery with continued antiepileptic drug (AED) treatment. We limit our discussion to failure to achieve long term surgical seizure control which can occur in three groups of patients. One, surgery fails with respect to seizure control with continued AEDs in one of three cases who never become seizure free after surgery. Two, a small subgroup of patients who were seizure free after surgery on AEDs will not remain seizure free in the long run. This is another group of patients in whom surgery may be considered to have failed. When AEDs are stopped in patients who have been seizure free after temporal lobe surgery for several years, one in three patients has a seizure recurrence. This is a third subgroup of patients in whom surgery has failed, particularly in a small group in whom reinstitution of AEDs after seizure recurrence fails to regain seizure freedom. Despite all these instances of failure, temporal lobe surgery is a very useful procedure and the only one which achieves seizure freedom in 50% of patients with drug resistant temporal lobe epilepsy, approximately in 20% of patients with AEDs and in 30% without AEDs.     

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 drugs management and long-term seizure outcome in post surgical mesial temporal lobe epilepsy with hippocampal sclerosis

Surgery is the treatment of choice for refractory temporal lobe epilepsies, but unexpected seizure recurrences occur and the AEDs management strategy may be an implicated factor. We evaluated the AEDs management's role in the outcome of post surgical epilepsy patients with hippocampal sclerosis (HS). Epileptic patients submitted to amigdalohippocampectomy due to HS in Engel class IA 12 months after surgery were selected. The following variables were studied: age, gender, time of post-surgical follow-up, present Engel class, number of antiepileptic AEDs before surgery and at the time of the interview, AED changes after surgery (stopped, increased, decreased, maintained), timing for AED changes after surgery and seizure recurrences. Sixty-seven consecutive patients were studied (mean time of follow-up of 4.9 ± 2.8 years). Among these, 46.3% were tapering AEDs, 38.8% had not changed and 14.9% had increased AEDs. The global recurrence rate was 32.8%. Recurrence rates for patients tapering and not tapering AEDs were similar (34.2% and 31%, respectively). Fifteen patients tapered AEDs before 2 years and 20 at or 2 years after surgery, with similar recurrence rates (33% and 30%, respectively). All patients who recurred due to AED tapering and 66.7% of the patients who recurred with no AED reduction resumed the Engel class I. This study suggests that in HS patients submitted to AHE who are seizure free during the first postsurgical year, AEDs tapering is achieved in a substantial percentage of patients. Tapering AEDs, independently of its timing, will induce seizure recurrence in about a third of patients. However, patients relapsing after tapering AEDs regain control after resuming therapy.     

Epilepsy surgery for pathologically proven hippocampal sclerosis provides long-term seizure control and improved quality of life

PURPOSE: To examine long-term seizure and quality-of-life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippocampal sclerosis (HS). Previous research has had limited follow-up (generally <2 years) and has grouped patients across multiple pathologies. METHODS: Fifty consecutive patients were identified as having had a temporal lobectomy for the treatment of temporal lobe epilepsy at Royal Melbourne Hospital with pathologically proven HS and >or=2 years' follow-up. All patients were sent a postal survey concerning seizure activity, quality of life (QOLIE-89), and antiepileptic drug (AED) use. The mean follow-up was 5.8 years (range, 2-9.2). RESULTS: The rate of complete postoperative seizure freedom was 82% at 12 months, 76% at 24 months, and 64% at 63 months (no further seizure recurrences observed after this time). A class I seizure outcome was achieved by 83.3% of patients. Patients with better seizure outcome had significantly better quality of life (Kendall's tau =-234, p < 0.01). Seizure recurrence was associated with a reduction in AED intake or absorption in five (29%) of 17 cases, including three of the five patients with a first seizure recurrence after 24 months after surgery. CONCLUSIONS: Temporal lobectomy provides continued long-term seizure control in the majority of patients with HS. However, patients remain at risk of seizure recurrence >or=2 years after surgery. Long-term quality of life is dependent on seizure outcome.     

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.     

The chance of cure following surgery for drug-resistant temporal lobe epilepsy. What do we know and do we need to revise our expectations?

Although surgery is often seen as a curative treatment for patients with drug-resistant temporal lobe epilepsy, little information is available how many cases can be considered cured after surgery, i.e. are seizure-free for several years without taking antiepileptic drugs (AEDs). In our review, 13 retrospective and five prospective clinical observations published since 1980 provided data on long-term seizure control off AEDs in a total of 1658 patients. No randomized studies were found. Following temporal lobe surgery, approximately one in four adult patients and approximately one in three children or adolescents can currently shown to be seizure-free for 5 years without AEDs (25%, mean of eight studies in adults, 95% CI: 21–30%, and 31%, mean of three studies in children, 95% CI: 20–41%). The rate of seizure control off AEDs seemed to be stable after 2 years of follow-up. However, as 55% of patients free of disabling seizures preferred not to discontinue their medication completely as late as 5 years after surgery, it is impossible to know if they are cured or not. No features predictive of surgical cure were detected except for better cure outcome in children versus adults with hippocampal sclerosis and in patients with typical versus atypical Ammonshorn's sclerosis or tumor in one small study each. In conclusion, the available evidence on seizure outcome off AEDs after temporal lobe surgery is based on non-randomized studies and, in part, data were collected retrospectively. A randomized controlled trial is needed to determine if, in fact only one in three to four patients with temporal lobe epilepsy undergoing surgery can be considered cured.     

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.     

Postoperative seizure control and antiepileptic drug use in pediatric epilepsy surgery patients: the UCLA experience, 1986-1997

PURPOSE: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long-term seizure control. METHODS: This study determined pre- and postsurgery seizure frequency and antiepileptic drug (AED) use (6 months to 10 years) in children with symptomatic seizures from unilateral cortical dysplasia (CD; n = 64) and non-CD etiologies (i.e., ischemia, infection; n = 71), and compared them with older temporal lobe epilepsy (TLE; n = 31) patients with complex partial seizures. RESULTS: Compared with presurgery, postsurgery seizure frequencies were decreased for CD, non-CD, and TLE patients (p < 0.002), and there were no differences between the three groups from 6 to 24 months after surgery (p > 0.12). At 5 years after surgery, seizure frequencies were greater in CD compared with TLE cases (p = 0.009). Compared with presurgery, the number of AEDs declined after surgery in all three groups (p < 0.002), and positively correlated with seizure frequencies (p = 0.0001). CONCLUSIONS: This study indicates that seizure relief and AED use after resective surgery for symptomatic CD and non-CD etiologies was comparable with complex partial TLE cases up to 2 years after surgery. Furthermore, at 5 years after surgery, CD patients had outcomes better than those before surgery, but worse than TLE cases. In young children, these findings support the concept that early removal of symptomatic pathologic substrates is associated with seizure control and reduced AED use, similar to that noted in older TLE cases up to 2 years after surgery. Seizure control may reduce the risk of developing the seizure-related encephalopathy associated with severe symptomatic early-onset childhood epilepsy.     

Management of antiepileptic drugs following epilepsy surgery: a review

The favourable impact of surgery for intractable epilepsy on seizures is well documented. However, few studies have determined what changes in antiepileptic drug (AED) therapy occur following surgery. Alterations in AED blood levels in the immediate postoperative period can result in breakthrough seizures. In long term follow-up, one-third to one-half of seizure-free patients after temporal lobectomy, the most common type of epilepsy surgery, still require AED treatment which usually has been reduced from polytherapy to monotherapy. In our study of 93 patients followed two years after temporal lobectomy, polytherapy decreased from 78% before surgery to 14% postoperatively, while medication was discontinued in 44%. Early reduction from polytherapy to monotherapy can often be carried out in the immediate postoperative period but the most appropriate timing of cessation of AED treatment has yet to be determined. Patients undergoing extratemporal resections and other forms of epilepsy surgery associated with less favourable postoperative seizure control may achieve comparatively less reduction in antiepileptic medication. We generally do not recommend stopping AEDs prior to one year after surgery.