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 outcome and its predictors after temporal lobe epilepsy surgery in patients with normal MRI

Purpose: To characterize seizure outcomes following temporal lobe epilepsy (TLE) surgery in patients with normal preoperative brain magnetic resonance imaging (MRI). Methods: We reviewed adult patients with pharmacoresistant epilepsy and normal MRI who underwent TLE surgery (1996–2009). Seizure outcomes were analyzed using survival and multivariate regression with Cox proportional hazard modeling. Two analyses were performed using two favorable outcome definitions: complete seizure freedom and Engel classification. Key Findings: Sixty‐four patients were analyzed (mean follow‐up 4.1 years; range 1–14.5 years). Most had a standard anterior temporal lobectomy (84%) and unremarkable pathology (45%). At 1 year, the chance of complete seizure freedom was 76% [95% confidence interval (CI) 71–81%] comparable to an 81% (95% CI 76–86%) chance of Engel score of 1. With longer follow‐up, a progressively broadening significant discrepancy between the two outcome measures was observed. The chance of complete seizure freedom was 66% (95% CI 61–71%) at 2 years, and 47% (95% CI 40–54%) at 7 years and beyond, whereas the respective chances of achieving an Engel 1 classification were 76% (95% CI 70–82%), and 69% (95% CI 63–75%) at similar time points. Seizure outcome as defined by either measure was worse in patients with higher baseline seizure frequency (adjusted risk‐ratio 2.7 when >12 seizures/month; p = 0.01) and with preoperative generalized tonic–clonic seizures (adjusted risk ratio 10.8; p = 0.0006). Memory measures declined with dominant hippocampus resections. Significance: A normal MRI should not prevent presurgical evaluations in patients with suspected TLE, as favorable long‐term postoperative seizure outcomes are possible. Proposed mechanisms of epileptogenicity and seizure recurrence in this group are discussed.     

When is a postoperative seizure equivalent to “epilepsy recurrence” after epilepsy surgery?

Purpose: Up to one‐half of epilepsy surgery patients will have at least one seizure after surgery. We aim to characterize the prognosis following a first postoperative seizure, and provide criteria allowing early identification of recurrent refractory epilepsy. Methods: Analyzing 915 epilepsy surgery patients operated on between 1990 and 2007, we studied 276 who had ≥1 seizure beyond the immediate postoperative period. The probability of subsequent seizures was calculated using survival analysis. Patients were divided into seizure‐free (no seizures for ≥1 year) and refractory (persistent seizures) and analyzed using multivariate regression analysis. Results: After a first seizure, 50% had a recurrence within 1 month and 77% within a year before the risk slowed down to additional 2–3% increments every two subsequent years. After a second seizure, 50% had a recurrence within 2 weeks, 78% within 2 months, and 83% within 6 months. Having both the first and second seizures within six postoperative months [odds ratio (OR) 4.04; 95% confidence interval (CI) 2.05–8.40; p = 0.0001], an unprovoked initial recurrence (OR 3.92; 95% CI 2.13–7.30; p < 0.0001), and ipsilateral spikes on a 6‐months postoperative electroencephalography (EEG) (OR 2.05; 95% CI 1.10–3.88; p = 0.025) predicted a poorer outcome, with 95% of patients who had all three risk factors becoming refractory. All patients with cryptogenic epilepsy and recurrent seizures developed refractoriness. Discussion: Seizures will recur in most patients who present with their first postoperative event, with one‐third eventually regaining seizure‐freedom. Etiology and early and unprovoked postoperative seizures with epileptiform activity on EEG at six postoperative months may predict recurrent medical refractoriness.     

Epilepsy surgery in tuberous sclerosis complex: Emphasis on surgical candidate and neuropsychology

Purpose: To discuss neuropsychological outcome and candidate of epilepsy surgery for tuberous sclerosis complex (TSC). Methods: To retrospectively analyze clinical data of 25 patients with TSC and epilepsy who underwent epilepsy surgery between 2001 and 2007. Seizure reduction was analyzed at 1‐year (1FU), 2‐year (2FU), and 5‐year (5FU) follow‐up visits after surgery, and outcomes of intelligence quotient (IQ) and quality of life (QOL) were evaluated at 2FU. Results: Resective procedures included 14 tuber resections, 9 lobectomies, and 2 tuber resections and lobectomies. Corpus callosotomies (CCTs) were performed as the adjunctive approach in eight cases with low IQ and behavioral problems. The percentages of seizure‐free cases were 72% at 1FU, 60% at 2FU, and 54.5% at 5FU, and the factors predicting seizure freedom included the course of seizures and ages of patients. Significant improvement was found in performance IQ in patients with preoperative low IQ or CCT. Significant improvement in mean QOL score was observed in all patients, especially patients with preoperative low IQ and CCT but postoperative seizure freedom. Conclusion: To be surgical candidates, patients with TSC and epilepsy should have identified epileptogenic tubers, and candidates should include patients with low IQ and multiple epileptogenic tubers. Satisfactory seizure control was often achieved with early operation, whereas improved QOL was observed frequently in postoperative seizure‐free patients. CCT could be performed as an adjunctive approach to resective operation for TSC patients with epilepsy and low IQ and render improvement of performance IQ and QOL.     

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.     

Race/ethnicity: a predictor of temporal lobe epilepsy surgery outcome?

PURPOSE: The success of epilepsy surgery in temporal lobe epilepsy reaches a 64% rate of seizure freedom, based on a randomized control trial. Observational studies from epilepsy centers worldwide indicate seizure freedom rates up to 93% when the etiology is unilateral hippocampal sclerosis. Several risk factors are attributed to the recurrence of seizures following the surgical procedure. Nonetheless, whether race influences the outcome of temporal lobe surgery is unknown. The purpose of this study was to evaluate if race plays a role in outcome following surgery. METHODS: Data were obtained from the discharge database of the University of Alabama at Birmingham video/EEG monitoring unit, between 1998 and 2003, as well as the clinical charts. Seizure recurrence was evaluated 1 year following surgery. The sample consisted of all patients with a primary diagnosis of mesial temporal sclerosis (MTS) who underwent anterior temporal lobectomy. Multiple logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for MTS. Two sets of logistic regression models were estimated to generate odds ratios (ORs) for seizure recurrence after an anterior temporal lobectomy for African-Americans or other possible ethnic/racial group present relative to non-Hispanic Caucasians. The first model incorporated only ethnicity as the independent variable and generated unadjusted ORs for seizure recurrence following the surgical procedure. The second set included the independent variables: duration of epilepsy, history of febrile seizures, lateralization of epileptogenic focus, handedness, and age. RESULTS: Seventy patients underwent surgical treatment and all of them had pathologic confirmation of MTS. Follow-up information for six was not available. Analysis of the remaining 64 patients revealed that African-Americans were more likely than non-Hispanic Caucasians to have seizure recurrence after surgery (OR=2.1, 95% CI=0.6-8.0). After potential confounders (duration of epilepsy, history of febrile seizures, lateralization of epileptogenic focus, handedness, and age) were controlled, this finding did not change (OR=1.7, 95% CI=0.3-10.7). CONCLUSION: Our data suggest that race may be an important factor related to seizure outcome following temporal lobectomy.     

Factors associated with seizure freedom in the surgical resection of glioneuronal tumors

Purpose: Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNETs) are low‐grade brain tumors of glioneuronal origin that commonly present with seizures. Achieving seizure control in patients with glioneuronal tumors remains underappreciated, as tumor‐related epilepsy significantly affects patients’ quality‐of‐life. Methods: We performed a quantitative and comprehensive systematic literature review of seizure outcomes after surgical resection of GGs and DNETs associated with seizures. We evaluated 910 patients from 39 studies, and stratified outcomes according to several potential prognostic variables. Key Findings: Overall, 80% of patients were seizure‐free after surgery (Engel class I), whereas 20% continued to have seizures (Engel class II–IV). We observed significantly higher rates of seizure‐freedom in patients with ≤1 year duration of epilepsy compared to those with >1 year of seizures [odds ratio (OR) 9.48; 95% confidence interval (CI) 2.26–39.66], and with gross‐total resection over subtotal lesionectomy (OR 5.34; 95% CI 3.61–7.89). In addition, the presence of secondarily generalized seizures preoperatively predicted a lower rate of seizure‐freedom after surgery (OR 0.40; 95% CI 0.24–0.66). Outcomes did not differ significantly between adults and children, patients with temporal lobe versus extratemporal tumors, pathologic diagnosis of GG versus DNET, medically controlled versus refractory seizures, or with the use of electrocorticography (ECoG). Extended resection of temporal lobe tumors, with hippocampectomy and/or corticectomy, conferred additional benefit. Significance: These results suggest that early operative intervention and gross‐total resection are critically important factors in achieving seizure‐freedom, and thus improving quality‐of‐life, in patients with glioneuronal tumors causing epilepsy.     

Long-term seizure outcome of surgery versus no surgery for drug-resistant partial epilepsy: A review of controlled studies

A majority of patients with formerly drug-resistant temporal lobe epilepsy become seizure-free after surgery. However, apart from one 12-month randomized trial, it is unclear how many become seizure-free because of surgery. To determine the net benefit of surgery, we performed a systematic review and meta-analysis of the published evidence of how many patients in similar studies become seizure-free without surgery. Of 155 potentially eligible articles reviewed in full text, 29 (19%) fulfilled eligibility criteria. After excluding 9 publications, 20 studies form the base of evidence. Overall, 719 of 1,621 (44%) of patients with mostly temporal lobe surgery were seizure-free compared to 139 of 1113 (12%) of nonoperated controls [pooled random effects relative risk (RR) 4.26, 95% confidence interval (CI) 3.03–5.98]. The pooled risk difference in favor of surgery was 42% (95% CI 32–51%). We found no comparative outcome data in patients with extratemporal lobe epilepsy only. The available evidence from mostly nonrandomized observational studies indicates that in appropriately selected patients with drug-resistant temporal lobe epilepsy, the combination of surgery with medical treatment is 4 times as likely as medical treatment alone to achieve freedom from seizures.     

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.     

Seizure clusters in drug‐resistant focal epilepsy

We investigated clinical factors associated with seizure clustering in patients with drug‐resistant focal epilepsy and any association between seizure clustering and outcome after surgery. We performed a retrospective study including patients with a diagnosis of drug‐resistant focal epilepsy who underwent epilepsy surgery. Patients were prospectively registered in a database from 1986 until 2015. Seizure cluster was defined as two or more seizures occurring within 2 days. Potential risk factors for seizure clustering were assessed. To investigate any potential association between seizure clusters and seizure outcome after surgery, time to event analysis was used to produce a Kaplan‐Meier estimate of seizure recurrence. We studied 764 patients. Seizure clusters were reported in 23.6% of patients with temporal lobe epilepsy (TLE) and 16.9% of extratemporal patients (p = 0.2). We could not identify any significant clinical factors associated with seizure clustering. Among patients with TLE, those who had history of seizure clusters fared better after surgery (p < 0.01). We found that seizure clusters relate to prognosis after temporal lobe surgery in drug‐resistant TLE. These data may provide added value for surgical prognostication when combined with other data types. A better understanding of the neurobiology underlying seizure clusters is needed.