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.     

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.     

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.     

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.     

Long‐term seizure outcome after resective surgery in patients evaluated with intracranial electrodes

Purpose: Despite advances in “noninvasive” localization techniques, many patients with medically intractable epilepsy require the placement of subdural (subdural grid electrode, SDE) and/or depth electrodes for the identification and definition of extent of the epileptic region. This study investigates the trends in longitudinal seizure outcome and its predictors in this group. Methods: We reviewed the medical records, and electroencephalography (EEG) data of 414 consecutive patients who underwent intracranial electrode placement (SDE and/or depth electrodes) at Cleveland Clinic Epilepsy Center between 1998 and 2008. A favorable outcome was defined as complete seizure freedom, discounting any auras or seizures that occurred within the first postoperative week. Survival curves were constructed, and Cox proportional hazard modeling was used to identify outcome predictors. Key Findings: The estimated probability of complete seizure freedom was 61% (95% confidence interval [CI] 58–64%) at one postoperative year, 47% (95% CI 44–50%) at 3 years, 42% (95% CI 39–45%) at 5 years, and 33% (95% CI 28–38%) at 10 years. Half of all seizure recurrences occurred within the first two postoperative months. Subsequently, the rate of seizure freedom declined by 4–5% every 2–3 years. After multivariate analysis, two independent predictors of seizure recurrence were identified: (1) prior resective surgery (p ≤ 0.002), mostly in patients with temporal lobe resections, and (2) sublobar or multilobar resection (p ≤ 0.02), mostly in patients following frontal lobe resections. Significance: Favorable seizure outcomes are possible in the complex epilepsy population requiring invasive EEG studies. We propose that mislocalization of the epileptogenic zone or its incomplete resection account for early postoperative recurrences, whereas epileptogenesis may lead to later relapses.     

Surgery for drug‐resistant tuberous sclerosis complex‐associated epilepsy: who,when, and what

Objective: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder associated with refractory early‐onset epilepsy. Current evidence supports surgery as the intervention most likely to achieve long‐term seizure freedom, but no specific guidelines are available on TSC pre‐surgical workup. This critical review assesses which TSC patients are suitable for surgical treatment, when pre‐surgical evaluation should start, and what degree of surgical resection is optimal for postsurgical outcome. Methods: We searched for publications from 2000 to 2020 in Pubmed and Embase using the terms “tuberous sclerosis,” “epilepsy,” and “epilepsy surgery”. To evaluate postsurgical seizure outcome, we selected only studies with at least one year of follow‐up. Results: Overall, we collected data on 1,026 patients from 34 studies. Age at surgery ranged from one month to 54 years. Mean age at surgery was 8.41 years. Of the diagnostic non‐invasive pre‐surgical tools, MRI and video‐EEG were considered most appropriate. Promising data for epileptogenic tuber detection is provided from invasive SEEG studies. Data on surgery and related outcome were available for 769 patients. Seizure freedom was seen in 64.4% of patients who underwent tuberectomy, 68.9% treated with lobectomy and 65.1% with multilobar resection. The most effective surgical approach was lobectomy, even though more recently tuberectomy associated with the resection of the perituberal area seems to be the best approach to reach seizure freedom. Published postsurgical seizure freedom rates in patients with TSC were between 65% and 75%, but reduced to 48%‐57% over longer follow‐up periods. Early surgery might positively affect neurodevelopmental trajectory in some patients, even though data on cognitive outcome are still to be confirmed with longitudinal studies. Significance: Considering the strong correlation between epilepsy duration and neurocognitive outcome, all patients with TSC ought to be referred early to a dedicated epilepsy centre for individually tailored pre‐surgical evaluation by a multi‐disciplinary epilepsy surgery team.     

Seizure worsening and its predictors after epilepsy surgery

Purpose: This study aims to investigate seizure worsening and its predictors after epilepsy surgery. Methods: A retrospective chart review of patients who underwent unilobar epilepsy surgery between 1990 and 2007 and had recurrence of at least one seizure was performed. Seizure worsening was defined as an increase in total average monthly seizure frequency, average monthly generalized tonic–clonic seizures (GTCS), new‐onset GTCS, or new‐onset status epilepticus. The occurrence of sudden unexpected death in epilepsy (SUDEP) was captured. Multivariate logistic regression analysis was used to identify predictors of worsening. Key Findings: A total of 276 patients with postoperative seizure recurrence were identified. Monthly average seizure frequency worsening occurred in 9.8%, GTC worsening in 8.0%, new‐onset GTCs in 1.4%, new‐onset status epilepticus in 2.2%, and death from SUDEP in 1.4%. A higher risk of worsening was seen with extratemporal resections as compared to temporal lobe surgeries (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.21–7.95; p = 0.018), and in patients with low preoperative seizure frequency <30 seizures/month (OR 14.82, 95% CI 2.81–275.41; p = 0.0003). Predictors of increased GTCs included an incomplete resection (OR 3.98, 95% CI 1.39–12.59; p = 0.010) and multiple recorded ictal patterns (OR 5.91, 95% CI 1.20–26.96; p = 0.030). Multiple seizure semiologies correlated with worsening after temporal lobe resections. Significance: The most vulnerable patients for seizure worsening following epilepsy surgery include those with extratemporal resections, incomplete resections, and multiple recorded ictal patterns.     

胶质瘤相关性癫痫术后疗效及影响因素分析

目的探讨胶质瘤相关性癫痫患者术后恢复情况,以及痫性再次发作的危险因素。方法收集89例胶质瘤相关性癫痫患者的一般资料。所有患者行肿瘤及致痫灶切除术,记录患者术后1周,术后1个月,术后3个月,术后6个月的Engle分级评分,其差别行组内重复测量资料的方差分析,应用Kaplan—Meier法制作痫性再发风险曲线,并对癫痫再次发作相关因素行Cox回归模型分析。结果术后癫痫再发率为26.97%(24/89),术后1周Engle分级评分为2.966±0.081,术后1月为2.202±0.080,术后3月为1.730±0.093,术后6月为1.313±0.042,差异存在统计学意义(F_(时间)=96.076,P0.01);Cox回归模型显示,肿瘤累及部位(RR=2.908,CI:1.083~7.806),术后水肿形成(RR=4.769,CI:1.737~13.096)以及肿瘤复发(RR=8.309,CI:3.379~20.432)是癫痫再次发作的重要危险因素(均P0.05)。结论术后患者的癫痫发作减少甚至消除,长期疗效优于短期疗效,对癫痫再次发作相关因素应尽早处理,有利于提高患者预后的生存质量。     

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.     

Remission of Seizures and Predictors of Intractability in Long-Term Follow-Up

In an incidence cohort, remission and relapse rates and determinants were studied in 178 patients followed long-term. A comparative study of predictive factors was performed in 40 patients with histories of antiepileptic (AED)-drug-refractory epileptic seizures in the last 10 years of follow-up and compared with the other 138 cohort subjects. The two groups were cross-tabulated with 353 variables of family history, obstetric, developmental and seizure histories, and current medical and social status. Multivariate analyses were applied for control of confounding. Defined or probable remote symptomatic etiology of seizures, abnormal neurologic development/ status, high initial seizure frequency, occurrence of status epilepticus, and poor short-term effects of AED therapy were significantly associated with long-term AED refractoriness. On logistic regression analyses, poor short-term outcome of AED therapy [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.2–10.4], occurrence of status epilepticus (OR 11.4; 95% CI 3.2–41.0), high initial seizure frequency (OR 4.6; 95% CI 1.1–19.3), and remote symptomatic seizure etiology (OR 2.9; 95% CI 1.1–8.2) remained the only independent predictors of seizure intractability. These factors enable early assessment of need for 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.     

Prognosis after temporal lobe epilepsy surgery: the value of combining predictors

Purpose: Although several independent predictors of seizure freedom after temporal lobe epilepsy surgery have been identified, their combined predictive value is largely unknown. Using a large database of operated patients, we assessed the combined predictive value of previously reported predictors included in a single multivariable model.
Methods: The database comprised a cohort of 484 patients who underwent temporal lobe surgery for drug-resistant epilepsy. Good outcome was defined as Engel class 1, one year after surgery. Previously reported independent predictors were tested in this cohort. To be included in our final prediction model, predictors had to show a multivariable p-value of <0.20.
Results: The final multivariable model included predictors obtained from the patient's history (absence of tonic–clonic seizures, absence of status epilepticus), magnetic resonance imaging [MRI; ipsilateral mesial temporal sclerosis (MTS), space occupying lesion], video electroencephalography (EEG; absence of ictal dystonic posturing, concordance between MRI and ictal EEG), and fluorodeoxyglucose positron emission tomography (FDG-PET; unilateral temporal abnormalities), that were related to seizure freedom in our data. The model showed an expected receiver-operating characteristic curve (ROC) area of 0.63 [95% confidence interval (CI) 0.57–0.68] for new patient populations. Intracranial monitoring and surgery-related parameters (including histology) were not important predictors of seizure freedom. Among patients with a high probability of seizure freedom, 85% were seizure-free one year after surgery; however, among patients with a high risk of not becoming seizure-free, still 40% were seizure-free one year after surgery.
Conclusion: We could only moderately predict seizure freedom after temporal lobe epilepsy surgery. It is particularly difficult to predict who will not become seizure-free after surgery.     

Discontinuation of anticonvulsant medication after epilepsy surgery in children

PURPOSE: To evaluate the long-term outcome of medication-reduction/discontinuation trials after epilepsy surgery in pediatric patients. METHODS: Of the total Bonn pediatric surgical sample (1988-2001; n=251), we were able to obtain postsurgical follow-up data for 232 patients. We surveyed 140 of these patients by using a standardized telephone interview that addressed medication-reduction/discontinuation trials. RESULTS: Of the 140 surveyed patients, 102 completely discontinued medication. Seven of these patients had recurring seizures that were controlled again after restarting the medication. Of 102 patients, 101 were completely seizure free during the 3 months before the survey. Postsurgical epileptic events before the trial significantly increased the risk for recurring epileptic events after the trial. Two surveyed patients lost postsurgical seizure freedom after medication reduction. We were also able to identify from the records another nine patients with complete medication discontinuation and seven patients with medication reduction. Two of these latter patients lost postsurgical seizure freedom despite restarting their medication. The total rate of patients with medication-reduction/discontinuation trials was 55%. The seizure recurrence rate in these patients was 10%. Recurring seizures could not be controlled by restarted medication in 3% of the trials. Currently, 90% of patients with discontinuation trials were seizure free without medication. CONCLUSIONS: The reduction/withdrawal of anticonvulsant medication after successful epilepsy surgery has a low risk of seizure recurrence for pediatric patients in long-term follow-up, particularly in cases of complete postsurgical seizure freedom before the trial.     

A longitudinal study of surgical outcome and its determinants following posterior cortex epilepsy surgery

Purpose:   To investigate the longitudinal seizure outcome and identify potential prognostic indicators following posterior cortex epilepsy (PCE) surgery.
Methods:   We reviewed patients who underwent a parietal, occipital, or parietooccipital resections between 1994 and 2006, using survival analysis and multivariate regression with Cox proportional hazard modeling. A favorable outcome was defined as Engel Class I at last follow-up.
Results:   Fifty-seven patients were identified with a mean follow-up of 3.3 years (range 1–12 years). The estimated chance of seizure freedom (SF) was 73.1% at 6 postoperative months, 68.5% at 1 year, 65.8% at between 2 and 5 years, and 54.8% at 6 years and beyond. Most recurrences (75%) occurred within the first 6 postoperative months. Parietal resections had a worse outcome than occipital or parietooccipital resections (52% SF vs. 89% and 93%, respectively, at 5 years). Independent predictors of recurrence included an epilepsy etiology other than tumor or dysplasia [risk ratio (RR) 2.29], limiting resection to a lesionectomy (RR 2.10), having ipsilateral temporal spiking on preoperative scalp electroencephalography (EEG) (RR 2.06), or any ipsilateral spiking on postoperative EEG (RR 2.70) (Log likelihood-ratio test p < 0.0001). Only 40–50% of patients with a poor outcome predictor were SF at 5 postoperative years as opposed to about 80% otherwise. In surgical failures, recurrent seizure frequency was related directly to baseline seizure frequency and to the presence of ipsilateral spiking on postoperative EEG.
Discussion:   These data highlight favorable long-term outcomes following PCE surgery. Limited surgical resection and diffuse baseline epileptogenicity may be important predictors of seizure recurrence.