Epilepsy is a devastating disease, often refractory to medication and not amenable to resective surgery. For patients whose seizures continue despite the best medical and surgical therapy, 3 stimulation-based therapies have demonstrated positive results in prospective randomized trials: vagus nerve stimulation, deep brain stimulation of the thalamic anterior nucleus, and responsive neurostimulation. All 3 neuromodulatory therapies offer significant reductions in seizure frequency for patients with partial epilepsy. A direct comparison of trial results, however, reveals important differences among outcomes and surgical risk between devices. The authors review published results from these pivotal trials and highlight important differences between the trials and devices and their application in clinical use.
John D. Rolston, Dario J. Englot, Doris D. Wang, Tina Shih and Edward F. Chang
Dario J. Englot, Doris D. Wang, John D. Rolston, Tina T. Shih and Edward F. Chang
Frontal lobe epilepsy (FLE) is the second-most common focal epilepsy syndrome, and seizures are medically refractory in many patients. Although various studies have examined rates and predictors of seizure freedom after resection for FLE, there is significant variability in their results due to patient diversity, and inadequate follow-up may lead to an overestimation of long-term seizure freedom.
In this paper the authors report a systematic review and meta-analysis of long-term seizure outcomes and predictors of response after resection for intractable FLE. Only studies of at least 10 patients examining seizure freedom after FLE surgery with postoperative follow-up duration of at least 48 months were included.
Across 1199 patients in 21 studies, the overall rate of postoperative seizure freedom (Engel Class I outcome) was 45.1%. No trend in seizure outcomes across all studies was observed over time. Significant predictors of long-term seizure freedom included lesional epilepsy origin (relative risk [RR] 1.67, 95% CI 1.36–28.6), abnormal preoperative MRI (RR 1.64, 95% CI 1.32–2.08), and localized frontal resection versus more extensive lobectomy with or without an extrafrontal component (RR 1.71, 95% CI 1.26–2.43). Within lesional FLE cases, gross-total resection led to significantly improved outcome versus subtotal lesionectomy (RR 1.99, 95% CI 1.47–2.84).
These findings suggest that FLE patients with a focal and identifiable lesion are more likely to achieve seizure freedom than those with a more poorly defined epileptic focus. While seizure freedom can be achieved in the surgical treatment of medically refractory FLE, these findings illustrate the compelling need for improved noninvasive and invasive localization techniques in FLE.
A systematic review
Dario J. Englot, John D. Rolston, Doris D. Wang, Peter P. Sun, Edward F. Chang and Kurtis I. Auguste
Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is responsible for 15%–20% of epilepsy cases in children. Class I evidence strongly supports the use of temporal lobectomy for intractable TLE in adults, but fewer studies have examined seizure outcomes and predictors of seizure freedom after temporal lobectomy in pediatric patients. The authors performed a systematic review and meta-analysis of studies including 10 or more pediatric patients (age ≤ 19 years) published over the last 20 years examining seizure outcomes after temporal lobectomy for TLE. Thirty-six studies met their inclusion criteria. These 36 studies included 1318 pediatric patients with a mean age (± SEM) of 10.7 ± 0.3 years. Overall, seizure freedom (Engel Class I outcome) was achieved in 1002 cases (76%); 316 patients (24%) continued to have seizures (Engel Class II–IV outcome). All patients had at least 1 year of follow-up. Statistically significant predictors of seizure freedom after surgery included lesional epilepsy etiology (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.02–1.15), abnormal findings on preoperative MRI (OR 1.27, 95% CI 1.16–1.40), and lack of generalized seizures (OR 1.36, 95% CI 1.20–1.56). Among lesional epilepsy cases, there was a trend toward better outcome with gross-total lesionectomy than with subtotal resection. Approximately three-fourths of pediatric patients with TLE attain seizure freedom after temporal lobectomy. Favorable outcomes may be predicted by lesional epilepsy etiology, abnormal MRI, and lack of generalized seizures. Pediatric patients with medically refractory TLE should be referred to a comprehensive pediatric epilepsy center for surgical evaluation.
Dario J. Englot, John D. Rolston, Doris D. Wang, Kevin H. Hassnain, Charles M. Gordon and Edward F. Chang
In the US, approximately 500,000 individuals are hospitalized yearly for traumatic brain injury (TBI), and posttraumatic epilepsy (PTE) is a common sequela of TBI. Improved treatment strategies for PTE are critically needed, as patients with the disorder are often resistant to antiepileptic medications and are poor candidates for definitive resection. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy that results in a ≥ 50% reduction in seizure frequency in approximately 50% of patients after 1 year of therapy. The role of VNS in PTE has been poorly studied. The aim of this study was to determine whether patients with PTE attain more favorable seizure outcomes than individuals with nontraumatic epilepsy etiologies.
Using a case-control study design, the authors retrospectively compared seizure outcomes after VNS therapy in patients with PTE versus those with nontraumatic epilepsy (non-PTE) who were part of a large prospectively collected patient registry.
After VNS therapy, patients with PTE demonstrated a greater reduction in seizure frequency (50% fewer seizures at the 3-month follow-up; 73% fewer seizures at 24 months) than patients with non-PTE (46% fewer seizures at 3 months; 57% fewer seizures at 24 months). Overall, patients with PTE had a 78% rate of clinical response to VNS therapy at 24 months (that is, ≥ 50% reduction in seizure frequency) as compared with a 61% response rate among patients with non-PTE (OR 1.32, 95% CI 1.07–1.61), leading to improved outcomes according to the Engel classification (p < 0.0001, Cochran-Mantel-Haenszel statistic).
Vagus nerve stimulation should be considered in patients with medically refractory PTE who are not good candidates for resection. A controlled prospective trial is necessary to further examine seizure outcomes as well as neuropsychological outcomes after VNS therapy in patients with intractable PTE.
Dario J. Englot, David Ouyang, Doris D. Wang, John D. Rolston, Paul A. Garcia and Edward F. Chang
Epilepsy surgery remains significantly underutilized. The authors recently reported that the number of lobectomies for localized intractable epilepsy in the US has not changed despite the implementation of clear evidence-based guidelines 10 years ago supporting early referral for surgery. To better understand why epilepsy surgery continues to be underused, the authors' objective was to carefully examine hospital-related factors related to the following: 1) where patients are being admitted for the evaluation of epilepsy, 2) rates of utilization for surgery across hospitals, and 3) perioperative morbidity between hospitals with low versus high volumes of epilepsy surgery.
The authors performed a population-based cohort study of US hospitals between 1990 and 2008 using the Nationwide Inpatient Sample (NIS), stratifying epilepsy surgery rates and trends as well as perioperative morbidity rates by hospital surgical volume.
The number of lobectomies for epilepsy performed at high-volume centers (> 15 lobectomies/year) significantly decreased between 1990 and 2008 (F = 20.4, p < 0.001), while significantly more procedures were performed at middle-volume hospitals (5–15 lobectomies/year) over time (F = 16.1, p < 0.001). No time trend was observed for hospitals performing fewer than 5 procedures per year. However, patients admitted to high-volume centers were significantly more likely to receive lobectomy than those at low-volume hospitals (relative risk 1.05, 95% CI 1.03–1.08, p < 0.001). Also, the incidence of perioperative adverse events was significantly higher at low-volume hospitals (12.9%) than at high-volume centers (6.1%) (relative risk 1.08, 95% CI 1.03–1.07, p < 0.001).
Hospital volume is an important predictor of epilepsy surgery utilization and perioperative morbidity. Patients with medically refractory epilepsy should be referred to a comprehensive epilepsy treatment center for surgical evaluation by an experienced clinical team.