Connectome biomarkers of drug‐resistant epilepsy

Drug‐resistant epilepsy (DRE) considerably affects patient health, cognition, and well‐being, and disproportionally contributes to the overall burden of epilepsy. The most common DRE syndromes are temporal lobe epilepsy related to mesiotemporal sclerosis and extratemporal epilepsy related to cortical malformations. Both syndromes have been traditionally considered as "focal," and most patients benefit from brain surgery for long‐term seizure control. However, increasing evidence indicates that many DRE patients also present with widespread structural and functional network disruptions. These anomalies have been suggested to relate to cognitive impairment and prognosis, highlighting their importance for patient management. The advent of multimodal neuroimaging and formal methods to quantify complex systems has offered unprecedented ability to profile structural and functional brain networks in DRE patients. Here, we performed a systematic review on existing DRE network biomarker candidates and their contribution to three key application areas: (1) modeling of cognitive impairments, (2) localization of the surgical target, and (3) prediction of clinical and cognitive outcomes after surgery. Although network biomarkers hold promise for a range of clinical applications, translation of neuroimaging biomarkers to the patient's bedside has been challenged by a lack of clinical and prospective studies. We therefore close by highlighting conceptual and methodological strategies to improve the evaluation and accessibility of network biomarkers, and ultimately guide clinically actionable decisions.     

Drug-resistant epilepsy in children with partial onset epilepsy treated with carbamazepine

Objective: To evaluate the outcome, including drug-resistant epilepsy (DRE) in children with newly diagnosed partial onset epilepsy treated with carbamazepine (CBZ). Methods: A retrospective medical records review and telephone questionnaire were undertaken on a total of 100 subjects. Results: Long-term follow-up was obtained on 79 children with a mean duration of 7.1 years from CBZ initiation. A total of 66 (83.5%) subjects achieved 2-year seizure remission, 48 (72.7%) subjects did so with CBZ monotherapy. Seven (10.6%) had seizure recurrence after 2-year seizure remission. DRE was diagnosed in seven (8.9%) subjects and five subjects had epilepsy surgery. The mean duration from seizure onset to epilepsy surgery was 5.3 (±2.1) years. Contributing factors for the prolonged duration from seizure onset to epilepsy surgery were identified including: relapsing–remitting course of seizure, family reluctance for epilepsy surgery and uncontrolled psychological problems. Conclusions: Over 80% of children with newly diagnosed partial onset epilepsy who were initially treated with CBZ achieved 2-year seizure remission, and more than 70% of this group did so with CBZ monotherapy. The majority of these patients maintained seizure remission overtime. However, 8.9% of this population met the criteria for DRE and most of them had epilepsy surgery. The duration from seizure onset to epilepsy surgery is an important potential area for improvement in DRE patient care.     

Cross-national disparities contribute to heterogeneity in patient outcomes following invasive monitoring: A hierarchical mixed-effects analysis

There is substantial variability in outcomes following invasive monitoring and surgical treatment of drug-resistant epilepsy (DRE). Patients with DRE are uniquely vulnerable to cross-national health care disparities, as their epilepsy is difficult to treat and requires extensive resources. In a large cross-national database of patients undergoing invasive monitoring for epilepsy surgery, we sought to evaluate the association between social, economic, and educational indicators of the country of treatment and patient outcomes following invasive monitoring. We performed a mixed-effects analysis of an individual patient database of 595 subjects enrolled in 33 studies encompassing 25 neurosurgical centers in 10 countries of invasive monitoring for epilepsy from 1996 to 2019. Upon preliminary univariate analysis, significant nation-level predictors of seizure outcome following either stereoelectroencephalography or subdural electrodes were hospital beds per 100,000 population, physician density, gross domestic product (GDP) growth, male and female educational attainment, and unemployment rate. On multivariate mixed-effects logistic regression, physician density (β = −0.5112, P<.00697) and GDP growth (β = 0.53822, P<.00404) were the only nation-level covariates of significance associated with seizure outcome. A higher physician density was associated with lesser seizure freedom rates, whereas higher GDP growth was associated with greater seizure freedom rates. Although patient-specific variables were the primary determinant of seizure outcomes, cross-national disparities also contribute to heterogeneities. Our findings highlight the importance of a systems-level dialogue to improve surgical outcomes for DRE patients.     

Research progress of vagus nerve stimulation in the treatment of epilepsy

The International League Against Epilepsy (ILAE) defined drug‐resistant epilepsy (DRE) that epilepsy seizure symptoms cannot be controlled with two well‐tolerated and appropriately chosen antiepileptic drugs, whether they are given as monotherapy or in combination. According to the WHO reports, there is about 30%‐40% of epilepsy patients belong to DRE. These patients need some treatments other than drugs, such as epilepsy surgery, and neuromodulation treatment. Traditional surgical approaches may be limited by the patient's clinical status, pathological tissue location, or overall prognosis. Thus, neuromodulation is an alternative choice to control their symptoms. Vagus nerve stimulation (VNS) is one of the neuromodulation methods clinically, which have been approved by the Food and Drug Administration (FDA). In this review, we systematically describe the clinical application, clinical effects, possible antiepileptic mechanisms, and future research directions of VNS for epilepsy.     

Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A “real-world” retrospective study

Objective

Recent clinical trials have shown that cenobamate substantially improves seizure control in focal-onset drug-resistant epilepsy (DRE). However, little is known about cenobamate's performance in highly active ( ≥ 20 seizures/month) and ultra-refractory focal epilepsy ( ≥ 6 failed epilepsy treatments, including antiseizure medications [ASMs], epilepsy surgery, and vagus nerve stimulation). Here, we studied cenobamate's efficacy and tolerability in a “real-world” severe DRE cohort.

Methods

We conducted a single-center retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment-emergent adverse events, and adjustments to concomitant ASMs were analyzed.

Results

Fifty-seven patients received cenobamate for at least 3 months (median duration, 11 months). The median cenobamate dose was 250 mg/day (range 75–350 mg). Baseline demographics were consistent with highly active (median seizure frequency, 60/month) and ultra-refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75%–99% reduction in seizures (42.1% of cohort), and 16 had a 50%–74% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic–clonic seizures in 55.6% (20/36) of patients. Among treatment responders, 67.4% (29/43) were treated with cenobamate doses of ≥ 250 mg/day. Three-fourths of patients reported at least one side-effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of ≥ 250 mg/day. Side-effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine, and perampanel.

Significance

Patients with highly active and ultra-refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250 mg/day may limit the potential for further improvements in seizure control at higher cenobamate doses.     

Outcome and long term follow-up after corpus callosotomy in childhood onset intractable epilepsy

Introduction Epilepsy surgery is a standard of care in the treatment of medically intractable epilepsy. Twenty five percent of patients with intractable epilepsy in childhood can be candidates for epilepsy surgery. Corpus callosotomy is a surgical treatment option for patients with potentially injurious drop attacks and disabling generalized seizures. Postoperative improvement of cognition and speech are important gains after epilepsy surgery particularly during childhood. The aim of this study is to evaluate the outcome of corpus callosotomy for the treatment of childhood onset medically intractable epilepsy in a developing pediatric epilepsy surgery center.Method We report 16 patients who underwent two thirds anterior corpus callosotomy for treatment of refractory seizures in childhood.Results All patients had drop attacks or multiple types of seizures, yet some showed focal onset with secondary generalization on electroencephalogram (EEG). One patient was seizure free (class 1 outcome), five had class 2A outcome, five had class 2B outcome, and five had class 3 outcome. Overall 11/16 (69%) of our patients improved significantly after anterior callosotomy.Conclusion Corpus callosotomy remains to be a fairly good choice of surgical treatment for childhood onset medically intractable epilepsy in selected patients.     

Use of intravenous immunoglobulins in drug-resistant epilepsy

Among the 257 pediatric patients examined, 104 were classified as having drug-resistant epilepsy (DRE). In all of them genetic, metabolic, chromosomal and infectious causes were investigated, and brain imaging with computed tomography scans and nuclear magnetic resonance were obtained. Since treatment with gammaglobulins (GGs) has been reported to be useful in pediatric cases of epilepsy, informed consent for GGs treatment was obtained in 43 patients with DRE. The etiology or evidence of brain lesions was identified in 16 of them. In 31 of these patients, neither conventional drug treatment, nor a trial with adrenocorticotropic hormone was successful. Intact monomeric GGs, 400 mg/kg, were given intravenously. A second dose was given after 15 days and, thereafter, every 21 days for a maximum of ten injections (protocol A), or every 2nd day for a maximum of five doses (protocol B). In every patient, the type of epilepsy was identified according to the classification of the International League Against Epilepsy. The frequency of seizures was recorded for a period beginning at least 6 months before the administration of GGs. Immunological evaluation was also performed before and after the treatment with GGs. A transient decrease of the seizure frequency was noted in 12 subjects. In another patient with infantile idiopathic myoclonic epilepsy, seizures disappeared for 30 months. In 1 case a persistent 80% reduction in the number of seizures was observed. A persistent disappearance of seizures was noted in a subject with complex partial seizures (CPS) that followed an idiopathic infantile spasm syndrome. In 2 more patients, 1 with grand mal status and another with idiopathic generalized tonic-clonic seizures (GTCS), seizures also disappeared, but the relationship to treatment with GGs was not straightforward. Treatment with GGs can be tried in cases of drug-resistant idiopathic GTCS, myoclonic or CPS when other treatments have failed.     

Patient attitudes about treatments for intractable epilepsy

OBJECTIVE: The goals of this study were to understand patient attitudes about the treatment of medically intractable epilepsy and to document potential barriers limiting patient access to the surgical treatment of epilepsy, highlighting the attitudes of adolescents and minorities. METHODS: Focus groups of adults with intractable epilepsy (n=10), adolescents with intractable epilepsy (n=4), parents of adolescents with intractable epilepsy (n=4), and African-Americans with intractable epilepsy (n=6) were conducted at UCLA, Los Angeles, California. RESULTS: Patients with intractable epilepsy communicated frustration with their continued disability despite trials of new medications. Their perceptions of the risks of the surgical treatment of epilepsy were exaggerated. Patients felt that their health care providers did not provide adequate information about epilepsy and portrayed epilepsy surgery negatively. CONCLUSIONS: This study illuminated several factors that could change patient attitudes and help improve patient access to the surgical treatment of epilepsy, especially among minorities and adolescents.     

Investigation of bias in an epilepsy machine learning algorithm trained on physician notes

Racial disparities in the utilization of epilepsy surgery are well documented, but it is unknown whether a natural language processing (NLP) algorithm trained on physician notes would produce biased recommendations for epilepsy presurgical evaluations. To assess this, an NLP algorithm was trained to identify potential surgical candidates using 1097 notes from 175 epilepsy patients with a history of resective epilepsy surgery and 268 patients who achieved seizure freedom without surgery (total N = 443 patients). The model was tested on 8340 notes from 3776 patients with epilepsy whose surgical candidacy status was unknown (2029 male, 1747 female, median age = 9 years; age range = 0‐60 years). Multiple linear regression using demographic variables as covariates was used to test for correlations between patient race and surgical candidacy scores. After accounting for other demographic and socioeconomic variables, patient race, gender, and primary language did not influence surgical candidacy scores (P > .35 for all). Higher scores were given to patients >18 years old who traveled farther to receive care, and those who had a higher family income and public insurance (P < .001, .001, .001, and .01, respectively). Demographic effects on surgical candidacy scores appeared to reflect patterns in patient referrals.     

The role of epilepsy surgery in southern Africa

Epilepsy surgery plays an important role in the management of patients with medically refractory temporal lobe epilepsy and lesional epilepsies. When performed early in the course of the illness, surgery can render many patients seizure-free and greatly improve their quality of life. In southern Africa, as in many developing nations, thousands of patients could benefit from epilepsy surgery, but inequalities in healthcare provision mean that ready access to surgical facilities is largely restricted to those with private healthcare insurance. Over the past 5 years, more than 250 patients have had epilepsy surgery in Cape Town; the cause of epilepsy in six of these individuals was neurocysticercosis resulting from central nervous system infection by the larval stage of the pork tapeworm ( Taenia solium ), which is a common cause of epilepsy in the tropics. In all cases, surgery was successful, with patients becoming seizure-free and reporting a much improved quality of life.     

Impact of epilepsy surgery on quality of life: Systematic review and meta-analysis

Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug-resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes. We conducted a systematic review and meta-analysis using Medline, Embase, and Cochrane Central Register of Controlled Trials. All studies reporting pre- and post-epilepsy surgery QoL scores in adults with DRE via validated instruments were included. Meta-analysis assessed the postsurgery change in QoL. Meta-regression assessed the effect of postoperative seizure outcomes on postoperative QoL as well as change in pre- and postoperative QoL scores. A total of 3774 titles and abstracts were reviewed, and ultimately 16 studies, comprising 1182 unique patients, were included. Quality of Life in Epilepsy Inventory–31 item (QOLIE-31) meta-analysis included six studies, and QOLIE-89 meta-analysis included four studies. Postoperative change in raw score was 20.5 for QOLIE-31 (95% confidence interval [CI] = 10.9–30.1, I² = 95.5) and 12.1 for QOLIE-89 (95% CI = 8.0–16.1, I² = 55.0%). This corresponds to clinically meaningful QOL improvements. Meta-regression demonstrated a higher postoperative QOLIE-31 score as well as change in pre- and postoperative QOLIE-31 score among studies of cohorts with higher proportions of patients with favorable seizure outcomes. At an individual study level, preoperative absence of mood disorders, better preoperative cognition, fewer trials of antiseizure medications before surgery, high levels of conscientiousness and openness to experience at the baseline, engagement in paid employment before and after surgery, and not being on antidepressants following surgery were associated with improved postoperative QoL. This study demonstrates the potential for epilepsy surgery to provide clinically meaningful improvements in QoL, as well as identifies clinicodemographic factors associated with this outcome. Limitations include substantial heterogeneity between individual studies and high risk of bias.     

Barriers toward epilepsy surgery. A survey among practicing neurologists

Purpose: Guidelines for refractory epilepsy recommend timely referral of potential surgical candidates to an epilepsy center for evaluation. However, this approach is seldom a priority for treating neurologists, possibly because of inertia of previous practice and personal attitudes, leading to a buildup of psychosocial disabilities and increased risk of morbidity and mortality. The aim of this study was to assess knowledge and attitudes toward epilepsy surgery among practicing neurologists and identify the barriers that delay the treatment. Methods: We surveyed 183 Italian adult and child neurologists with an ad hoc questionnaire exploring physicians’ willingness to refer patients for epilepsy surgery when such treatment may be indicated. Thirteen of 14 questions had graded answers ranging from 1 (unfavorable to surgery) to 10 (favorable). We compared the overall scores and per‐question scores of the neurologists versus a group of academic and clinical leaders in the field. Key Findings: The neurologists gave responses characterized by extreme variability (i.e., wide response interquartile range) around intermediate scores. Experts had higher and less variable scores favoring surgery. The two groups differed significantly on issues such as how long to pursue pharmacologic treatment and information about indications and outcome of surgery. Multivariate analysis indicated that neurologists’ attitudes correlated with the number of patients referred for surgery (p < 0.01) and the geographical region where specialty was attained (p < 0.01). Other variables such as years in practice, number of patients treated for epilepsy, or type of specialty had no predictive value on physicians’ behavior. Significance: The majority of Italian neurologists have highly variable attitudes toward epilepsy surgery, reflecting ambivalence and uncertainty toward this type of treatment. About two thirds of responders are nonaligned with the opinion leaders, mainly due to differences in handling pharmacologic treatment and information regarding epilepsy surgery, which affect their attitudes and ultimately patient management. Strategies that may solve the lack of agreement include reinforcing the concept of pharmacoresistance and associated risks, as opposed to the safety and potential benefits of surgery, the use of epilepsy quality measures during follow‐up, and the adoption of structured referral sheets and greater involvement of patients in decision making. These measures should facilitate the referral of potential candidates for surgical evaluation and improve overall quality of care.     

病灶性癫痫的手术治疗及影响其预后的因素分析

目的 探讨病灶性癫痫的手术方法，并分析影响手术预后的一些因素。方法 回顾性地分析自2001年4月～2003年4月之间在我研究所接受手术治疗的所有病灶性癫痫患者的临床资料。33例患者手术后随访时间皆在1年或1年以上。按照Engel疗效分级标准，将其分为效果满意组与不满意组，对术前临床特点、电生理情况、手术方法等因素进行分析比较。结果 手术后效果满意率为73％。下列因素与手术效果有相关性：癫痫患病时间、发作频率以及脑电图发作间期痫性放电是否局限在病灶的脑叶上。另一方面，比较发病时年龄、是否有既发全面强直阵挛性发作以及是否完全切除术中皮层脑电监测(ECoG)为阳性的皮层三个因素，两组间无显著差异。不满意组中，皮质发育不全的患者占多数。结论 对于病灶性癫痫，手术采用病灶与周围致痫灶同时切除的方法，可获得满意的效果。癫痫患病时间、发作频率以及脑电图发作间期痫性放电是否局限在病灶的脑叶上与手术的效果有一定的相关性。     

The multicenter study of epilepsy surgery: recruitment and selection for surgery

PURPOSE: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single-center series with limited sample size. Little information is available about the selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries. METHODS: An observational cohort of 565 surgical candidates was prospectively recruited from June 1996 through January 2001 at six Northeastern and one Midwestern surgical centers. Standardized eligibility criteria and protocol for presurgical evaluations were used at all seven sites. RESULTS: Three hundred ninety-six (70%) study subjects had resective surgery. Clinical factors such as a well-localized magnetic resonance imaging (MRI) abnormality and consistently localized EEG findings were most strongly associated with having surgery. Of those who underwent intracranial monitoring (189, 34%), 85% went on to have surgery. Race/ethnicity and marital status were marginally associated with having surgery. Age, education, and employment status were not. Demographic factors had little influence over the surgical decision. More than half of the patients had intractable epilepsy for >/=10 years and five or more drugs had failed by the time they initiated their surgical evaluation. During the recruitment period, eight new antiepileptic drugs were approved by the Food and Drug Administration for use in the United States and came into increasing use in this study's surgical candidates. Despite the increased availability of new therapeutic options, the proportion that had surgery each year did not fluctuate significantly from year to year. This suggests that, in this group of patients, the new drugs did not provide a substantial therapeutic benefit. CONCLUSIONS: Up to 30% of patients who undergo presurgical evaluations for resective epilepsy surgery ultimately do not have this form of surgery. This is a group whose needs are not currently met by available therapies and procedures. Lack of clear localizing evidence appears to be the main reason for not having surgery. To the extent that these data can address the question, they suggest that repeated attempts to control intractable epilepsy with new drugs will not result in sustained seizure control, and eligible patients will proceed to surgery eventually. This is consistent with recent arguments to consider surgery earlier rather than later in the course of epilepsy. Postsurgical follow-up of this group will permit a detailed analysis of presurgical factors that predict the best and worst seizure outcomes.     

Surgery for epilepsy: a review

This year marks the centennial of the first surgical resection for epilepsy performed by Horsley. While epilepsy is generally considered a disease best treated with anticonvulsant medications, surgical therapy is of significant benefit to some patients in whom medical therapy has proved ineffective. Anterior temporal lobectomy has been the single most successful operation commonly performed today. In this paper we review current techniques of preoperative evaluation, the role of scalp and intracranial electrophysiologic monitoring, as well as the contribution of PET and MRI scanning to improving the selection of patients for surgical therapy. The role of focal cortical excisions, hemispherectomy, and corpus callosotomy in the surgical armamentarium is also outlined. A plea is made for establishment of additional regionalized centers for epilepsy surgery in which close collaboration among neurologists, neuropsychologists, neurosurgeons and neurophysiologists can enhance patient care and advance our knowledge of the partial epilepsies and human cerebral function.     

Cost-effectiveness analysis of epilepsy surgery in children and adolescents with drug resistant focal epilepsy at three years in a tertiary care epilepsy center in Thailand

Epilepsy surgery is proven as a cost-effective treatment in developed countries, especially in adults with drug resistant epilepsy (DRE). This study is aimed to demonstrate the cost-effectiveness of epilepsy surgery in children and adolescents with DRE at three years compared with those who were eligible for surgery but received medical treatment. This study was conducted from January 2014 to December 2018. Clinical data were obtained from a retrospective chart review. Direct medical costs, including epilepsy surgery, inpatient and outpatient treatment were retrieved from the finance department. Direct non-medical costs were collected from the family interview. The effectiveness was determined by percent seizure reduction and quality of life assessed by EQ-5D scores. Decision tree analysis using TreeAge Pro® 2018 was deployed to determine the cost-effectiveness. Seventeen patients had epilepsy surgery and 19 were in the medical group. Seizure freedom was noted in 52% and 16% in the surgical and medical groups, respectively. Incremental cost-effectiveness ratio (ICER) was 743,040 THB (22,793 USD) per 1 QALY and 3302 THB (101 USD) per 1% seizure reduction. The study did not demonstrate cost-effectiveness of epilepsy surgery in the short term compared with Thailand’s threshold (160,000 THB (4908 USD) per 1 QALY). Epilepsy surgery may be cost-effective if evaluated beyond three years.     

Outcome of epilepsy surgery correlates with sympathetic modulation and neuroimaging of the heart

Temporal lobe epilepsy (TLE) is frequently associated with sympathetic over-activity. Single photon emission computed tomography (SPECT) with 123iodine-meta-iodobenzylguanidine (MIBG), a norepinephrine analogue, showed reduced tracer uptake in cardiac sympathetic nerve endings, indicating myocardial catecholamine disturbance. We investigated whether outcome of epilepsy surgery correlates with cardiac autonomic function in TLE patients.We studied 16 TLE patients before and after epilepsy surgery. We recorded heart rate (HR) and determined sympathetic and parasympathetic cardiac modulation as powers of low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) heart rate oscillations. The LF/HF-ratio was calculated as index of sympathovagal balance. Cardiac MIBG uptake was assessed with MIBG-SPECT and compared to control data.After surgery, eight patients were seizure-free and eight had persistent seizures. Sympathetic LF-power and LF/HF-ratio were higher in patients who had persistent seizures than in patients who became seizure-free. After surgery, both parameters decreased in seizure-free patients but increased in patients with persistent seizures. MIBG uptake was lower in patients than controls and even lower in the patient subgroup who had persistent seizures. In this subgroup, MIBG uptake further decreased after surgery (P<0.05).Sympathetic cardiac modulation decreased in TLE patients after successful surgery, but further increased if seizures persisted. Reduction of cardiac MIBG uptake progressed after surgery in patients with persistent seizures. Interference of epileptogenic discharges with autonomic neuronal transmission might account for sympathetic cardiac over-stimulation and reduced MIBG uptake. Both findings are possible risk factors for sudden unexplained death and might be relevant for risk stratification in epilepsy patients.     

Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia

OBJECTIVES: To determine the surgical outcome and prognostic factors in adult patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS AND METHODS: We retrospectively studied the operative outcome in 21 consecutive adult patients with FCD who underwent surgical treatment for intractable partial epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years). The median post-operative follow-up was 2.5 years. The FCD was extratemporal in 11 patients, involved the temporal lobe in 10 patients, and was multilobar in eight patients. Eleven patients (52%) were rendered seizure-free, four patients (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94% reduction in seizures. A seizure-free outcome was associated with shorter duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be candidates for surgical treatment of intractable partial epilepsy. Most individuals have neocortical, extrahippocampal seizures and approximately 50% of patients are rendered seizure-free.     

Epilepsy surgery,antiepileptic drug trials,and the role of evidence

Objective: We assessed whether recent randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) are informed by evidence about surgical effectiveness. We explored whether RCTs of AEDs consider the patients’ candidacy for surgery in their eligibility criteria, and whether the necessary investigations are requested in participating patients to determine their potential eligibility for surgery. Methods: We systematically analyzed RCTs published in the last 2 years investigating the efficacy of new AEDs in localization‐related epilepsy. Results from a surgical RCT and recommendations from an epilepsy surgery practice parameter were used to assess the degree to which surgical evidence informed the drug study design. Results: Eleven RCTs were analyzed. All were conducted in countries with access to epilepsy surgery. None of the studies required magnetic resonance imaging (MRI) with an epilepsy protocol or explicit statement of the epilepsy syndrome, which could lead to the identification of surgical candidates. Having temporal lobe epilepsy or being a potential surgical candidate were not exclusion criteria in any of the trials. The primary efficacy end point was the reduction in seizure frequency or responder rate. Seizure freedom was never the primary outcome, and it was reported in only seven studies. The pooled data analysis of these trials revealed that 1.9% of patients became seizure‐free on placebo and 4.4% on the study drug (p < 0.01). Conclusions: Important aspects of patient selection for new AED trials are not informed by the evidence about surgical effectiveness. Investigations that could lead to identification of patients for presurgical evaluation were not required in any of the studies.     

Multiple subpial transections: the Yale experience

PURPOSE: Although resection of an epileptogenic region is the mainstay of epilepsy surgery, epileptogenic areas in functionally critical cortex cannot be approached in that manner. Multiple subpial transection (MST) was developed to treat those refractory seizures without causing unacceptable neurologic deficit. We review our experience with this technique. METHODS: Twelve patients who underwent MST with or without resection between 1990 and 1998 were retrospectively reviewed with regard to seizure and neurologic outcome, and predictive factors. RESULTS: Five (42%) of 12 patients obtained a significant improvement in seizure frequency, and two other patients had a marked decrease in the severity of their seizures. Resection with MST reduced seizure frequency more, but this was not a significant difference. No predictive factors for outcome were identified. Only one patient sustained any persistent neurologic deficit. CONCLUSIONS: In selected patients, MST may be a viable alternative when the epileptogenic focus lies in unresectable cortex. A multicenter study with appreciable patient numbers will be necessary to define predictive factors for success.