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

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

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.     

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.     

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 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.     

The prognostic significance of interictal epileptiform activity in postoperative EEGs of patients with mesial temporal lobe epilepsy.

It has not been established whether electroencephalography (EEG) is a contributing factor in predicting the outcome of surgery for epilepsy. We conducted a prospective study on 26 patients (M/F 14/12, age: 33 +/- 7.5 years, range 19-48) with mesial temporal lobe epilepsy (MTLE) who were followed for 2 years after surgery and who underwent routine EEG recordings 5.6 +/- 3 months (range 3-12) postoperatively. Interictal epileptiform activity (IEA) on the EEG was compared in 17 seizure-free patients to 9 patients with recurrent seizures. The two groups were similar in gender, age, febrile convulsions, trauma, family history, seizure frequency prior to surgery, epilepsy duration and number of antiepileptic drugs. Following surgery, 17 study patients (65%) became seizure free; 9 (35%) had seizure recurrence. Post-operative EEG recordings showed IEA in 8/26 study patients (31%), 3 of whom were from the seizure-free group (3/17, 18%); 5 had seizure recurrence (5/9, 56%) (p=0.078). IEAs in postoperative EEGs were less frequently demonstrated in patients who were seizure free, but the presence of postoperative IEAs does not preclude successful surgical outcome.     

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.     

Prognostic factors for the surgery for mesial temporal lobe epilepsy: longitudinal analysis

PURPOSE: Determining long-term prognostic factors of surgery for mesial temporal lobe epilepsy (MTLE) is important for identifying ideal candidates and predicting the prognosis for individual patients. We tried to identify the prognostic factors of anterior temporal lobectomy (ATL) for MTLE with longitudinal multivariate analysis. METHODS: Two hundred twenty-seven patients with MTLE were included in this study. The primary outcome variable was patient status 1-5 years after surgery: seizure free, or not. Clinical characteristics and recent diagnostic modalities were considered as prognostic factors. Univariate and standard multiple logistic-regression analysis for outcome at 1 and 5 years after surgery and the generalized estimation equation (GEE) model for longitudinal multiple logistic regression of the 5-year follow-up period were used. RESULTS: The seizure-free rate at 1 year was 81.1% and decreased to 75.2% at 5 years after surgery. By the univariate or standard multiple logistic-regression analysis, age at surgery or hippocampal sclerosis on magnetic resonance imaging (MRI) ipsilateral to surgery was significant for the postsurgical outcome. However, the longitudinal analysis by the GEE model revealed that younger age at surgery [odds ratio (OR), 0.59; 95% confidence interval (CI), 0.43-0.81], absence of secondarily generalized tonic-clonic seizure (2 degrees GTCS; OR, 0.45; 95% CI, 0.26-0.79), and hippocampal sclerosis on MRI (OR, 2.44; 95% CI, 1.11-5.26) were significant predictors of a good surgical outcome. CONCLUSIONS: Age at surgery, presence of 2 degrees GTCS, and hippocampal sclerosis on MRI are independent prognostic factors for ATL in MTLE. These findings suggest that MTLE is a progressive disorder, and surgical outcome is better when early ATL is performed.     

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.     

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.     

Comparison of short-term outcome between surgical and clinical treatment in temporal lobe epilepsy: a prospective study.

OBJECTIVE: To compare the efficacy of medical and surgical treatment for refractory mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE). METHODS: A prospective controlled non-randomized study of 26 patients with MTLE who underwent surgical treatment and 75 patients with MTLE who underwent medical treatment between August 2002 and October 2004. All patients failed to achieve seizure control with at least two first line antiepileptic drugs (AED) for partial seizures before entering the study. We used Kaplan-Meier survival analyses as a function of time of seizure recurrence to obtain estimates of 95% confident interval of seizure freedom and log-rank test to compare the status of seizure control between the two groups. RESULTS: The cumulative proportion of patients free of all seizures (Engel's class IA) was higher in the surgical group (73%) compared to the clinical group (12%) (p<0.0001). In the surgical group, 2 of 26 patients (7.7%) had transient adverse effects and 2 of 26 patients (7.7%) had a permanent deficit related to the surgical procedure. In the clinical group 7 patients (9.3%) major adverse events during follow-up, including burns and status epilepticus. CONCLUSIONS: Surgical treatment for patients with MTLE who failed to achieve seizure control with two previous AED regimens was more efficient than medical treatment with further trials of AED.     

Seizure outcomes following multilobar epilepsy surgery

Purpose: Outcomes following unilobar surgeries for refractory epilepsy have been well described. However, little is known about long‐term seizure outcomes following multilobar resections. The aim of the current study was to identify long‐term seizure control and predictors of seizure recurrence in this patient population. Methods: Records of patients who underwent multilobar epilepsy surgery at the Cleveland Clinic between 1994 and 2010 were retrospectively reviewed. A postoperative follow‐up of at least 6 months was required. Patients were classified as seizure free if they achieved an Engel class I at last follow‐up. Long‐term chances of seizure freedom were illustrated using a survival analysis, and predictors of recurrence were identified using Cox proportional hazard modeling. Key Findings: Sixty‐three patients with medically intractable epilepsy underwent multilobar surgical resections during the study period (mean follow‐up of 4.6 years). Predominant resection types included extended occipital (temporoparietooccipital, parietooccipital, temporooccipital: 57%), frontotemporal (21%), and temporoparietal (17%). Mean age at surgery was 21.4 years and mean age at seizure onset was 10.1 years. Fifty‐six percent of the patients underwent extraoperative invasive electroencephalography (EEG) evaluations. At 6 postoperative months, 71% (95% confidence interval (CI) 65–77) were seizure‐free (SF), 64% (CI 58–70) were SF at 1 year, 52% (CI 46–59) were SF at 5 years, and 41% (CI 32–50) remained SF at 10 years. Forty‐one patients had at least one breakthrough seizure after surgery (median timing of recurrence 6.1 months), with an Engel class 1 achieved again by last follow‐up in 12 of these 41 cases. Nine patients required a reoperation. Patients who underwent extended occipital/posterior quadrant resections had more favorable outcomes as compared to the other groups. With multivariate analysis, the type of resection (p = 0.03), preoperative auras (p = 0.03), an incomplete resection (0.03), and the presence of postoperative spikes (p = 0.0003) correlated with seizure recurrence. The risk of seizure recurrence for an incomplete resection was 2.3 (CI 1.53–3.36), preoperative aura 2.3 (CI 1.34–3.87), and postoperative spikes on surface EEG 2.5 (CI 1.29–4.71). Significance: A favorable outcome can be achieved in 41% of patients undergoing multilobar resections for epilepsy surgery at 10 years of follow‐up. Close to one‐third of patients who have breakthrough seizures after surgery are able to regain seizure freedom by last follow‐up. Predictors of recurrence include resection type (frontotemporal and parietotemporal resections did worse), presence of preoperative aura, an incomplete surgical resection, and the presence of postoperative interictal discharges on EEG.     

Benign mesial temporal lobe epilepsy: A clinical cohort and literature review

ObjectiveWe present a single-center retrospective study of benign mesial temporal lobe epilepsy (bMTLE) between 1995 and 2014.MethodsHospital records and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG), imaging features, and response to treatment with antiepileptic drugs (AEDs) were documented. Patients were included in this study if they were seizure-free for a minimum of 24 months with or without an AED.ResultsTwenty-seven patients were identified. There were 19 (70%) females, mean age at first seizure was 32.2 (range: 15–80 years). In all patients, seizures were mild, and seizure freedom was readily achieved with the initiation of AED therapy. Sixteen patients (59%) had mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue AED therapy after a prolonged period of remission (5–8 years), but all had seizure recurrence within 2 to 4 weeks.SignificanceNot all temporal lobe epilepsy is refractory to medication, despite the presence of MTS. Until clinical trials indicate otherwise, surgery is not indicated but life-long medical treatment is advocated.     

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.     

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.     

Does early postoperative drug regimen impact seizure control in patients undergoing temporal lobe resections?

Objective

To evaluate the impact of postoperative antiepileptic drug (AED) load on seizure control in patients who underwent surgical treatment for pharmacoresistant mesiotemporal lobe epilepsy during the first two postoperative years.

Patients and methods

532 consecutive patients (48.7% males and 51.7% females) who underwent surgical treatment for mesiotemporal lobe epilepsy were retrospectively evaluated regarding effects of AED load on seizures control during the first 2 years following epilepsy surgery. We analyzed whether postoperative increases in postoperative AED load are associated with better seizure control in patients initially not seizure free, and if postoperative decreases in postoperative AED load would increase the risk for seizure persistence or recurrence. For statistical analyses, Fisher’s exact and Wilcoxon test were applied.

Results

68.9, 64.0 and 59.1% of patients were completely seizure free (Engel Ia) at 3, 12 and 24 months after surgery, respectively. Patients in whom daily drug doses were increased did not have a higher rate of seizure freedom at any of the three follow-up periods. Of 16 patients achieving secondary seizure control at 12 months after surgery, only one did so with an increase in drug load in contrast to 15 patients who experienced a running down of seizures independent of drug load increases. Decreases in drug load did not significantly increase the risk for seizure recurrence. Of postoperatively seizure free patients at 3 months after surgery in whom AED were consequently reduced, 85% remained completely seizure free at 1 year and 76% at 1 year after surgery, respectively, as opposed to 86% each when AED was not reduced (differences n.s.). Mean daily drug load was significantly lower in seizure free patients at 12 and 24 months compared to patients with ongoing seizures.

Conclusion

In this large patient cohort stratified to the epilepsy syndrome neither did a postoperative reduction in drug load significantly increase the risk for seizure relapse nor did increases in drug dosages lead to improved seizure control. Mean drug load was on average lower in seizure free- than non-seizure free patients at 12 and 24 months of follow-up. Secondary seizure control after initial postoperative seizures in > 90% of cases occurred as a running down, independent of an AED increase. Thus, the effect of the surgical intervention rather than the postoperative drug regimen was the key determinant for seizure control. This finding supports a curative role of temporal lobe surgery rather than an effect rendering the majority of patients’ pharmacoresponsive with a critical role of the antiepileptic drug regime for seizure control.

     

Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients

OBJECTIVE: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. METHODS: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. RESULTS: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p < or = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome. CONCLUSIONS: Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.     

Long-term seizure outcome and risk factors for recurrence after extratemporal epilepsy surgery

Purpose: We aimed to assess long‐term seizure outcome and risk factors for seizure recurrence in a cohort of patients who have undergone extratemporal resection for management of refractory seizures. Methods: Eighty‐one patients underwent extratemporal resection at Austin Health, Melbourne, Australia (1991–2004). Seizure recurrence was any postoperative disabling seizure (complex partial seizure [CPS] ± secondary generalization). Multivariate Cox proportional hazards regression models examined potential preoperative and perioperative risk factors and the risk associated with early postoperative seizures (≤28 days postsurgery). The change between preoperative and postoperative seizure frequency was also measured. Key Findings: Median follow‐up was 10.3 years (range 1–17.7). The probabilities of freedom from disabling seizures (on or off antiepileptic medication) were 40.7% (95% confidence interval [CI] 30–51) at 1 month, 23.5% (95% CI 15–33) at 1 year, and 14.7% (95% CI 8–23) at 5 years postoperative. Reduction of disabling seizures to at least 20% of preoperative frequency was attained by 57% of patients at 5 postoperative years. Of the preoperative/perioperative factors, focal cortical dysplasia (FCD) type 1 (hazard ratio [HR] 1.90, 95% CI 1.08–3.34, p = 0.025) and incomplete resection (HR 1.71, 95% CI 1.06–2.76, p = 0.028) were independent recurrence risks. After surgery, an early postoperative seizure was the only factor associated with higher risk (HR 4.28 [2.42–7.57], p = 0.00). Significance: Distinction between subtypes of focal cortical dysplasia, which can be made using magnetic resonance imaging (MRI) criteria, may be useful for preoperative prognostication. Early seizures after surgery are not benign and may be markers of factors that contribute to seizure recurrence. Most patients achieve substantial reduction in seizure frequency. Further study of the significance of this reduction in terms of surgical “success” or otherwise is required.     

Seizure Frequency and Duration of Epilepsy are Not Risk Factors for Postoperative Seizure Outcome in Patients with Hippocampal Sclerosis

PURPOSE: Despite accurate localization of the seizure focus, not all patients are seizure free after temporal lobectomy. This study determined risk factors for seizure recurrence in patients with proven hippocampal sclerosis. METHODS: The outcome from surgery was assessed in 56 consecutive patients with proven hippocampal sclerosis. The age at surgery, duration of epilepsy, history and age of febrile seizures, age of onset of epilepsy, sex ratio, laterality of seizure focus, and seizure frequency were compared between patients seizure free and those not seizure free, and those seizure and aura free and those with seizure recurrence including auras. RESULTS: During a mean follow-up of 38 months, 48 (86%) of 56 are seizure free. The mean age at surgery (37 vs. 36 years), duration of epilepsy (26 vs. 22 years), age (1.6 vs. 1.1 years), and occurrence (58 vs. 75%) of febrile seizures, age of onset of epilepsy (11 vs. 14 years), sex ratio (50 vs. 75% female), laterality of seizure focus (42 vs. 50% left), greater than weekly seizures (40 vs. 38%), and a history of (69 vs. 75%) and frequency of (2.10 vs. 2.38 per year) secondarily generalized seizures did not differ significantly between the two groups. Similarly there was no significant difference between patients seizure and aura free and those with seizure recurrence including auras. CONCLUSIONS: Clinical factors such as seizure frequency and duration of epilepsy are not risk factors for postoperative seizure recurrence.