Resective Surgery For Intractable Epilepsy Research Articles

The localization and lateralization of fear aura and its surgical prognostic value in patients with focal epilepsy.

ObjectiveFear aura has traditionally been considered relevant to epileptic discharges from mesial temporal areas, and few studies have investigated its effect on surgical outcome in drug‐resistant epilepsy. We aim to assess the localizing and lateralizing value as well as prognostic significance of fear aura in patients with focal epilepsy.MethodsThe occurrence of fear aura in relation to epileptogenic origin and its association with postoperative outcome were analyzed in 146 consecutive patients undergoing resective surgery for intractable epilepsy.ResultsNinety‐four (64.4%) patients reported auras, and 31 (21.2%) reported fear aura in their seizures. One hundred ten (75.3%) patients had an Engel class I outcome until last follow‐up, of whom 24 experienced fear aura preoperatively. Fear aura appeared more frequently during temporal and frontal lobe seizures, but did not lateralize the seizure onset zone. There were no significant baseline differences between patients with and without fear aura. No correlation was found between postoperative outcome and the presence of auras. Occurrence of fear aura failed to show predictive value in surgical outcome whether in pooled or subgroup analysis.InterpretationThis study advances our understanding of the origin of fear aura, and is helpful for presurgical evaluation and outcome prediction. Without lateralizing value, fear aura is more commonly seen with temporal or frontal origin. When taken as a whole, auras do not have a significant impact on seizure outcome in focal epilepsy. Patients with fear aura are no more likely to become seizure‐free than those without fear aura.

Additional resective surgery after the failure of initial surgery in patients with intractable epilepsy

ObjectivesThere are three conceivable reasons for the failure of resective surgery for intractable epilepsy: incomplete resection of the epileptogenic zone including or overlapping with eloquent area (group A); incorrect determination of the epileptogenic zone prior to the first surgery (group B); and the development of a new epileptic focus after the first surgery (group C). We examined the relationship between the reason for failure of initial surgery and patient outcomes after repeated surgical resection.MethodsThe study included 18 patients (5.1%) underwent additional surgery after failure of the initial operation. Post-operative outcomes, complications and other clinical data were collected by retrospective chart review.ResultsFour patients (22.2%) were assigned to group A, 13 (72.2%) were assigned to group B, and 1 patient was assigned to group C (5.6%). Six patients (40.0%) were seizure-free for 2 or more years after additional surgery. In group B, 11 patients underwent additional resection of the cortex adjacent to the previously resected area and 2 underwent re-operation involving a site distant from the previously resected area; notably, the latter 2 patients did not achieve seizure-free status post-surgery. After the first operation, only one patient (group A) experienced transient paresis; after additional surgery, 10 of 18 patients (56%; 3 group A, 6 group B, and 1 group C) experienced various complications.DiscussionAlthough additional resective surgery provided freedom from seizures in about 40% of the patients, it is important to weigh a high risk of complications against possible benefits when considering additional surgery.

Long-term seizure and psychosocial outcomes after resective surgery for intractable epilepsy

Resective surgery is considered an effective treatment for refractory localization-related epilepsy. Most studies have reported seizure and psychosocial outcomes of 2–5years postsurgery and a few up to 10years. Our study aimed to assess long-term (up to 15years) postsurgical seizure and psychosocial outcomes at our epilepsy center. The Henry Ford Health System Corporate Data Store was accessed to identify patients who had undergone surgical resection for localization-related epilepsy from 1993 to 2011. Demographics including age at epilepsy onset and surgery, seizure frequency before surgery, and pathology were gathered from electronic medical records. Phone surveys were conducted from May 2012 to January 2013 to determine patients' current seizure frequency and psychosocial metrics including driving and employment status and use of antidepressants. Surgical outcomes were based on Engel's classification (classes I and II=favorable outcomes). McNemar's tests, chi-square tests, two sample t-tests, and Wilcoxon two sample tests were used to analyze the relationships of psychosocial and surgical outcomes with demographic and surgical characteristics. A total of 470 patients had resective epilepsy surgery, and of those, 50 (11%) had died since surgery. Of the remaining, 253 (60%) were contacted with mean follow-up of 10.6±5.0years (27% of patients had follow-up of 15years or longer). Of the patients surveyed, 32% were seizure-free and 75% had a favorable outcome (classes I and II). Favorable outcomes had significant associations with temporal resection (78% temporal vs 58% extratemporal, p=0.01) and when surgery was performed after scalp EEG only (85% vs 65%, p<0.001). Most importantly, favorable and seizure-free outcome rates remained stable after surgery over long-term follow-up [i.e., <5years (77%, 41%), 5–10years (67%, 29%), 10–15years (78%, 38%), and >15years (78%, 26%)]. Compared to before surgery, patients at the time of the survey were more likely to be driving (51% vs 35%, p<0.001) and using antidepressants (30% vs 22%, p=0.013) but less likely to be working full-time (23% vs 42%, p<0.001). A large majority of patients (92%) considered epilepsy surgery worthwhile regardless of the resection site, and this was associated with favorable outcomes (favorable=98% vs unfavorable=74%, p<0.001). The findings suggest that resective epilepsy surgery yields favorable long-term postoperative seizure and psychosocial outcomes.

Effectiveness of levetiracetam use following resective surgery in patients with refractory epilepsy: A prospective observational study

This study aimed to evaluate the effectiveness of levetiracetam (LEV) use for seizure control in patients who had undergone resective surgery for intractable epilepsy in routine clinical practice. This was a prospective, observational study. Refractory epilepsy patients who underwent epilepsy surgery from January 2008 to December 2011 in the Department of Neurosurgery, West China Hospital were prospectively analyzed. Patients were divided into two groups according to antiepileptic drug (AED) treatment used immediately after epilepsy surgery (group A: therapy with LEV; group B: therapy without LEV). AED regimens were compared with regard to seizure-outcome for a period of more than 2 years. The International League Against Epilepsy (ILAE) classification was used to categorize seizure outcome. A total of 319 patients (184 male and 135 female patients; mean age 28.2±13.4 years) were studied. The mean postoperative follow-up period was 3.9±1.2 years. The two groups showed was no significant difference in preoperative baseline data. At the 6-month follow-up, the proportion of patients with seizure freedom was significantly higher in group A than in group B (78.8% vs. 67.5%, p=0.03). Seizure outcomes after 2 years were assessed using the ILAE classification. The proportion of patients under ILAE seizure-outcome classification I (seizure freedom) was significantly higher in group A than in group B (74.3% vs. 60.7%, p=0.01). Seizure recurrence rates at the final assessment, after planned reduction or withdrawal, were 26.3% for group A and 40.6% for group B (p=0.04). AED strategy after resective surgery may be a potentially modifiable prognostic indicator influencing seizure outcome in patients with intractable epilepsy. Compared to other AEDs, LEV appears to be more effective in controlling postoperative seizures in our long-term follow-up, and the advantage can be seen in early stage after surgery.

Seizure Control Following Palliative Resective Surgery for Intractable Epilepsy—A Pilot Study

BackgroundPatients with intractable epilepsy who have bilateral epileptic foci may not qualify for curative epilepsy surgery. In some cases palliative resection may be undertaken with a goal to decrease seizure frequency and improve quality of life. Here we present data on the outcome of palliative epilepsy surgery in children. MethodsWe reviewed medical charts of children who underwent palliative resection for intractable epilepsy during the years 1999-2013 at Children's Hospital of Michigan. The palliative intent of resection was declared preoperatively. Outcome was assessed in terms of seizure reduction. ResultsThere were 18 patients (11 males, median age of surgery was 3.5 years [range 0.5-16 years]). The median duration of follow-up after surgery was 12.5 months (range 6-60 months). Hemispherectomy was the most commonly performed palliative resection (nine patients), followed by lobectomy (six patients), multilobar resection (one patient), and tuberectomy (two patients). Reduction in seizure frequency was observed in 11 patients, with eight patients achieving seizure freedom on antiepileptic drugs and three with >50% reduction in seizure frequency. Transient improvement in seizure frequency occurred in two patients, whereas there was no benefit in five patients. ConclusionsBeneficial effects of epilepsy surgery may be realized in carefully selected situations wherein the most epileptogenic focus is resected to reduce seizure burden and improve quality of life.

Predictors of seizure freedom after incomplete resection in children

Incomplete resection of the epileptogenic zone (EZ) is the most important predictor of poor outcome after resective surgery for intractable epilepsy. We analyzed the contribution of preoperative and perioperative variables including MRI and EEG data as predictors of seizure-free (SF) outcome after incomplete resection. We retrospectively reviewed patients <18 years of age with incomplete resection for epilepsy with 2 years of follow-up. Fourteen preoperative and perioperative variables were compared in SF and non-SF (NSF) patients. We compared lesional patients, categorized by reason for incompleteness, to lesional patients with complete resection. We analyzed for effect of complete EEG resection on SF outcome in patients with incompletely resected MRI lesions and vice versa. Eighty-three patients with incomplete resection were included with 41% becoming SF. Forty-eight lesional patients with complete resection were included. Thirty-eight percent (57/151) of patients with incomplete resection and 34% (47/138) with complete resection were excluded secondary to lack of follow-up or incomplete records. Contiguous MRI lesions were predictive of seizure freedom after incomplete resection. Fifty-seven percent of patients incomplete by MRI alone, 52% incomplete by EEG alone, and 24% incomplete by both became SF compared to 77% of patients with complete resection (p = 0.0005). Complete resection of the MRI- and EEG-defined EZ is the best predictor of seizure freedom, though patients incomplete by EEG or MRI alone have better outcome compared to patients incomplete by both. More than one-third of patients with incomplete resection become SF, with contiguous MRI lesions a predictor of SF outcome.

Oligoastrocytoma presenting with intractable epilepsy

Oligoastrocytomas (OA) are mixed gliomas with distinct oligodendroglial and astrocytic neoplastic components. Very little about OA has been reported in the intractable epilepsy population. We undertook a retrospective review of 923 patients who underwent resective surgery for intractable epilepsy between 1996 and 2004. 6/923 (0.7%) patients were diagnosed with OA. Five patients were female, one was male. Median age at diagnosis was 25 years (range 19-44 years). Tumors arose from the left side in all patients and from the temporal lobe in five patients. Three patients had complex partial seizures. Median length of refractory epilepsy prior to surgery was 10.5 years (range 1-28 years), and the median number of antiepileptic drugs used was 2 (range 1-10). Preoperative WADA testing for language and memory localization was done for three patients; preoperative stereotactical localization was done for three patients. Surgical pathology revealed low-grade OA (WHO II) in five patients, and anaplastic OA in one. There were no surgical complications, clinical or radiographic tumor recurrence at a mean follow up period of 3.2 years (range 2-8). Excellent seizure freedom was achieved in 5/6 patients. As a result of our small sample size, general conclusions may be imprecise, but this review suggests that OA behave similar to other tumors related to intractable epilepsy: they usually have a preoperative seizure course of many years, an excellent rate of seizure-freedom following surgery, and are in general, low-grade tumors with an indolent course for which serial imaging is sufficient follow-up.

Advances in the Radiosurgical Treatment of Epilepsy

Radiosurgery is the precise application of focused radiation to a targeted volume area within the brain, which has been identified on MRI. With recent advances, radiosurgical treatment is now being evaluated as an alternative treatment to open resective surgery for intractable epilepsy. Recent prospective trials suggest that radiosurgery may be an effective and safe treatment for medically intractable epilepsy associated with mesial temporal sclerosis, cavernous malformations, and hypothalamic hamartomas.

Heterogeneous GABAA receptor subunit expression in pediatric epilepsy patients

The gamma-amino-butyric acid type A receptors (GABAAR) are a heteropentameric receptor complex, composed of 16 possible subunits in various combinations, forming a ligand-gated ion channel. Subunit composition is the primary determinant of GABAAR physiology and pharmacology. Here we have measured mRNA levels for 16 GABAAR subunits in isolated dentate granule neurons (DGN) from eight pediatric patients undergoing resective surgery for intractable epilepsy. We found tightly correlated expression of a subset of GABAAR subunit mRNAs within a single DGN (alpha1, gamma1, and gamma2; alpha4, alpha5, and beta2; alpha4 and beta3). Analysis of inter-patient variability (ANOVA) of eleven highly expressed GABAAR subunit mRNAs found seven of the subunits varied between patients, as did whole cell GABAAR currents. Due to inter-patient differences, there is heterogeneity in DGN GABAAR subunit mRNA and physiology within pediatric epilepsy patients. Patient-specific GABAAR expression might contribute to variability in anti-epileptic drug efficacy, side-effect profiles, and seizure susceptibility.

Long-term seizure outcome in patients initially seizure-free after resective epilepsy surgery.

To evaluate the likelihood of and risk factors for seizure recurrence in patients initially seizure-free after resective surgery for intractable epilepsy. One hundred seventy-five patients who underwent lobectomy between 1972 and 1992 and were seizure-free during the first postoperative year were retrospectively studied. Outcome was measured by relapse risk, presence of auras in otherwise seizure-free patients, and seizure frequency among relapsers. Factors significant in bivariate or Kaplan-Meier analysis or considered potentially predictive a priori were included in multivariate models. Of the 175 patients (mean follow-up 8.4 years), 63% never relapsed. The likelihood of being seizure-free was 83 +/- 6% 3 years after surgery, 72 +/- 7% after 5 years, and 56 +/- 9% after 10 years. After adjusting for age at surgery, duration of preoperative epilepsy, and resection site, normal pathology was associated with increased risk of relapse compared to mesial temporal sclerosis or other pathology (p = 0.036; hazard ratio [HR] 2.38; 95% CI 1.06 to 5.34). Among patients otherwise seizure-free, preoperative illness of > or =20 years was associated with increased risk of postoperative auras (p = 0.040; HR 3.55; 95% CI 1.06 to 11.90). Among relapsers, 51% experienced one or fewer seizures per year. Normal pathology and earlier relapse were associated with higher postoperative seizure frequency. In patients seizure-free during the first year after resective epilepsy surgery, the likelihood of remaining seizure-free declined to 56% over 10 years, but half of patients who relapsed had at most one seizure per year. Longer preoperative illness and normal pathology predicted poorer outcome.

Natural History of Recurrent Seizures After Resective Surgery for Epilepsy

Seizures persist or recur in 20-60% of patients after resective surgery for intractable partial epilepsy. Further information about the natural course of these seizures is lacking in the literature. During one decade of epilepsy surgery at a single institution, we identified 72 patients with recurrent postoperative seizures after resective procedures for epilepsy. Prospectively compiled seizure diaries, hospital records, and outpatient office records were reviewed and supplemented by telephone communications to assess subsequent seizure frequency. Follow-up data was available ranging from 6 months to 7 years 5 months (mean 3 years 5 months). The likelihood of persistent seizures and recurrent intractability was examined with life-tables. Seizures recurred within the first postoperative year in 86% of patients and were similar to preoperative events in 74% of patients. After the first seizure recurrence, there was 80% likelihood of persistent seizures in the next 6 years and 40% likelihood of intractability (more than one seizure a month despite optimal medical therapy). The interval until recurrence within the first postoperative year did not affect the likelihood of subsequent seizures or intractability. Late seizure recurrence (after the first year) was not associated with any instances of subsequent intractability. Recurrent seizures after extratemporal resections were more likely to become persistent and intractable than seizures recurring after temporal resections. This information provides rational prognostication and assists in counseling patients with recurrent seizures after resective surgery for intractable epilepsy.

Predictive value of intraoperative electrocorticograms in resective epilepsy surgery

The preresection and postresection intraoperative electrocorticograms of 76 consecutive patients undergoing resective surgery for intractable epilepsy were analyzed to see if location, configuration, and discharge rate of epileptiform activity correlated with type and location of pathology of the resected specimens and outcome in regard to seizure control. The location of the predominant spike focus did not correlate with either type of location of pathology or with seizure outcome from temporal lobe surgery (n = 58). The presence of spontaneous or activated spikes outside the resected area did not correlate with outcome from any surgery type. Positive spikes recorded from the amygdala and anterior hippocampus (n = 37) were not associated with type or location of pathology, but bursts of fast repetitive spikes on these needle recordings tended to associate with mesiotemporal pathology (p = less than 0.02) and with mesial temporal sclerosis (p = less than 0.04). A preresection spike discharge rate of 1 per 4 minutes or less was associated with a poor outcome in 5 of 6 patients (p = 0.03), whereas a rate of 18 or more per minute was associated with a good outcome in 15 of 18 patients (p less than 0.06). Persistence of 50% or more of the preresection epileptiform activity in the postresection electrocorticogram after temporal lobectomy correlated with poor outcome in 80% (p = less than 0.03), although the absolute amount of epileptiform activity remaining in the postresection electrocorticogram did not correlate with outcome. Further studies are needed to define the role of intraoperative electrocorticograms in resective epilepsy surgery.

Selection of patients with chronic drug-resistant epilepsy for resective surgery: 5 years' experience.

Selection criteria are the key to success in resective surgery for intractable epilepsy. Using such criteria about 50% of patients admitted for assessment are considered unsuitable, half of these for neurophysiological reasons or because there is evidence of more than one area of structural abnormality. Selection for a good result from temporal lobectomy can be judged, both on the proportion of positive pathological lesions in the resected temporal lobes and on a high degree of seizure relief together with a low incidence of side effects. The same holds for other resections. The relationship between these factors is reviewed.