Key Points
Question
What are the outcomes of laser interstitial thermal therapy (LITT) for patients with mesial temporal lobe epilepsy (MTLE)?
Findings
In this cohort study of 145 patients with MTLE undergoing LITT, a majority of patients reached Engel 1 and International League Against Epilepsy 1/2 outcomes at 24 months, with improved quality of life at nearly all time points.
Meaning
The findings suggest that LITT may provide patients with MTLE with a minimally invasive and safe option for durable seizure control and quality of life improvements.
This cohort study evaluates the use of laser interstitial thermal therapy in patients with mesial temporal lobe epilepsy.
Abstract
Importance
Laser interstitial thermal therapy (LITT) is a surgical tool used to ablate epileptic foci and brain tumors. Understanding clinical and procedural outcomes of LITT for mesial temporal lobe epilepsy (MTLE) is relevant to clinicians and patients.
Objective
To describe seizure outcomes, procedural outcomes, and safety data of MTLE LITT.
Design, Setting, and Participants
Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN) is a prospective multicenter registry with up to 5 years of follow-up lasting from October 2015 to March 2023 at LAANTERN epilepsy sites, which are all level IV National Association of Epilepsy Centers in the US. Adult and pediatric LAANTERN enrollees undergoing LITT for drug-resistant MTLE with at least 6 months of follow-up were included. Those with epilepsy related to a malignant lesion were excluded.
Intervention
LITT for drug-resistant MTLE.
Main Outcomes and Measures
Demographic, epilepsy, and seizure characteristics; procedural data; postsurgical seizure outcomes; safety data; and quality of life (QOL) scores were prospectively collected.
Results
Fifteen centers enrolled 145 patients (73 [50.3%] female) with MTLE undergoing LITT, with 77 reaching 2-year follow-up. The mean (SD) age was 39.2 (15.4) years at time of LITT with 14 of 145 in the pediatric range (younger than 22 years). The 2 most common etiologies were mesial temporal sclerosis (n = 74) and unknown etiology or magnetic resonance imaging normal (n = 31). Mean (SD) ablation volume was 28.2 (29.8) mL. Mean (SD) surgery duration was 4.3 (2.1) hours, and mean (SD) blood loss was 22 (17.6) mL. Median (IQR) length of stay was 1 (1-3) day, and 33 patients (23%) had no intensive care unit stay postprocedure. Median (IQR) intensive care unit time was 22 (19.2-28.8) hours. Mean (SD) discharge head pain score was 2.1 (2.6) on a 0-10 scale. Most patients (n = 140 [96.6%]) were discharged home. Two-year seizure outcomes were 45 of 77 (58.4%) and 44 of 77 (57.2%) for Engel 1 and International League Against Epilepsy 1/2, respectively. No clinical characteristics were associated with seizure outcome. Adverse events were seen in 24 patients (16.5%), most being mild and transient. Pediatric seizure outcomes were similar to adult outcomes. One-third of patients stopped or decreased their antiseizure medicines. Improvements in QOL scores were seen at almost all time points assessed.
Conclusions
In the largest prospective multicenter MTLE LITT cohort, LITT was found to be well tolerated with clinically meaningful seizure outcomes and QOL improvements. These findings indicate that LITT may be considered as a treatment option for drug-resistant MTLE.
Introduction
The use of laser interstitial thermal therapy (LITT) for surgical treatment of drug-resistant epilepsy (DRE) is increasingly standard at epilepsy centers.1 Possible reasons for adoption include general preference for a minimally invasive option, low complication rates relative to anterior temporal lobectomy (ATL),2,3 low patient-reported pain, and decreased hospitalization lengths.4,5,6 This use follows demonstrated effectiveness from mainly retrospective single-center and fewer multicenter studies, particularly for mesial temporal lobe epilepsy (MTLE).4,7,8,9,10,11,12,13,14,15 Wu et al7 suggested that the targeting of specific mesial temporal regions was associated with improved outcomes, a finding that has been reproduced by others.16,17 Thus, the majority of retrospective research has demonstrated LITT to be an accepted epilepsy surgical tool.
With LITT’s adoption at epilepsy centers, there remains interest in effects on quality of life (QOL). A meta-analysis18 demonstrated improved QOL following epilepsy surgery, particularly with favorable seizure outcomes. Pertinently, that study of 1182 patients included only 10 patients undergoing LITT, so additional data are needed to assess post-LITT QOL outcomes. Separately, 296 of 406 patients with DRE (73%) stated a surgical option should be considered vs continuing antiseizure medication (ASM) alone. A strong preference for minimally invasive procedures (321 of 406 [79%]) over open brain surgery (85 of 406 [21%]) was also noted. Respondents were willing to accept a lower treatment benefit in exchange for reduced mortality or neurological deficit risk,6 which LITT has been shown to have.5
Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN) is a multicenter prospective registry of patients undergoing LITT with up to 5-year follow-up. We discuss final outcomes of patients with MTLE in LAANTERN. Neuropsychological outcomes for patients with epilepsy in LAANTERN were assessed in a later companion study (Patient Neuropsychological Outcomes After Laser Ablation [PENSAR]; NCT05075850).
Methods
Patient Enrollment
LAANTERN is an institutional review board–approved, prospective registry across 28 institutions in the US allowing 5-year follow-up data post-LITT. Fifteen institutions enrolled participants for this analysis. Further LAANTERN details were previously described.4,19,20,21,22 Data monitoring and management with source verification were used to ensure deidentified data accuracy. Written informed consent was obtained for all participants. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
For this analysis, patients with MTLE in LAANTERN who had 6 or more months of follow-up were included. Patients with epilepsy related to a malignant lesion were excluded, although epilepsy-specific lesions were included. All patients in LAANTERN were consecutively enrolled at each institution between October 2015 and March 2023. Pediatric patient classification used the US Food and Drug Administration (FDA) definition of younger than 22 years at the time of LITT procedure.23
Surgical Management
All centers used the FDA-510(k)–cleared NeuroBlate System (Monteris Medical) as previously described.24 Surgical preplanning and technique varied per standard of care at each institution.
Variables Collected
Demographic characteristics, health history information, and disease-specific outcome measures were collected. The following variables were assessed: demographic characteristics, epilepsy localization, epilepsy etiology, seizure types, presurgical testing, ASMs, ablation size, surgical skin-to-skin time, total ablation time, total energy applied to the lesion, adverse events (AEs), hospitalization data, seizure outcomes, and 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) scores.25
An independent safety committee composed of neurosurgeons with laser ablation expertise reviewed AEs. The committee adjudicated AEs into neurological vs nonneurological and mild, moderate, or severe categories. Neurological deficits were specified as temporary or permanent. Relatedness to the NeuroBlate system, LITT procedure, and surgical procedure itself were also adjudicated.
Statistical Analysis
Categorical variables were summarized at the individual level using relative frequencies and percentages. Continuous variables were summarized using means with SDs, medians with IQRs, and minimum vs maximum. If a participant had multiple lesions ablated, the largest lesion volume and percent ablated were reported.
For QOLIE-31 and pain scores, paired t tests were used to compare scores from each follow-up time point to baseline. Multivariable logistic regression was used to model odds of an Engel score of 1 or International League Against Epilepsy (ILAE) score of 1 or 2 at 12 and 24 months. Covariates included in the model were focal aware seizures (auras); race (Black, White, and other) and ethnicity (Hispanic and non-Hispanic), collected via patient self-report and reported because we sought to understand if there were racial or ethnic differences in MTLE LITT outcomes; mesial temporal sclerosis (MTS); focal to bilateral tonic clonic (FBTC) semiology; and drug resistance for 6 or more years (compared to 0-5 years of drug resistance).
For historical control analysis, an independent t test was used to test for significant difference in the mean age of LAANTERN individuals with Wiebe et al.26 Fisher exact test was used to test for significant differences among the remaining variables.
All reported P values were 2-sided, and a P value less than .05 was considered statistically significant. All statistical analyses were performed using Stata version 18.0 (StataCorp).
Results
Demographic Characteristics
There were 145 patients (73 [50.3%] female and 72 [49.7%] male; 13 [9.0%] Black, 119 [82.1%] White, and 13 [9.0%] other [including Asian, multiple races, and unknown, consolidated for patient privacy]; 18 of 144 reported [12.5%] Hispanic and 126 [87.5%] non-Hispanic ethnicity) with MTLE in this cohort, 14 of whom were pediatric. Demographic and seizure characteristics are shown in Table 1. The mean (SD) epilepsy onset age was 20.4 (13.6) years, and the mean (SD) age at time of LITT was 39.2 (15.4) years with 14 of 145 in the pediatric range. The 2 most common epilepsy etiologies were MTS and magnetic resonance imaging normal, most had more than 3 ASMs fail, 67 (47.5%) had auras, and 79 (56%) had FBTC semiology. Ancillary evaluation is shown in eTable 1 in Supplement 1.
Table 1. Patient Characteristics.
| Variable | Participants, No. (%) (N = 145) |
|---|---|
| Age at time of LITT, mean (SD), y | 39.2 (15.4) |
| Sex | |
| Female | 73 (50.3) |
| Male | 72 (49.7) |
| Racea | |
| Black | 13 (9.0) |
| White | 119 (82.1) |
| Otherb | 13 (9.0) |
| Ethnicity, No./total No. (%)a | |
| Hispanic | 18/144 (12.5) |
| Non-Hispanic | 126/144 (87.5) |
| Seizure presentation and history, No. | 142 |
| Age at seizure onset, mean (SD), y | 20.4 (13.6) |
| Type of seizures | 141 |
| Aura or focal aware | 67 (47.5) |
| Motor aware | 10 (7.1) |
| Motor unaware | 55 (39.0) |
| Dyscognitive or focal impaired awareness | 40 (28.4) |
| Focal to bilateral tonic clonic or generalized bilateral tonic clonic | 79 (56.0) |
| Other | 8 (5.7) |
| Epilepsy etiology | 141 |
| Mesial temporal sclerosis | 74 (52.5) |
| Unknown | 25 (17.7) |
| Posttraumatic | 13 (9.2) |
| Magnetic resonance imaging normal | 6 (4.3) |
| Genetic | 5 (3.5) |
| Cavernoma | 4 (2.8) |
| Poststroke | 3 (2.1) |
| Focal cortical dysplasia | 3 (2.1) |
| Neoplasia | 2 (1.4) |
| Immune | 2 (1.4) |
| Encephalocele | 1 (0.7) |
| Infections | 1 (0.7) |
| Heterotopia | 1 (0.7) |
| DNET | 1 (0.7) |
| Polymicrogyria, metabolic, tuberous sclerosis, ganglioglioma, other neoplasia | 0 (0) |
| History of previous treatments | 125 |
| Amygdalohippocampectomy/anterior lobectomy/hippocampectomy/lesion resection | 18 (14.4) |
| LITT | 5 (4.0) |
| Corpus callosotomy/multiple subpial transection | 1 (0.8) |
| Vagus nerve stimulation | 15 (12.0) |
| No. of medications failed | 136 |
| 1 | 1 (0.7) |
| 2 | 22 (16.2) |
| 3 | 15 (11.0) |
| >3 | 98 (72.1) |
| Time since drug resistance, y | 106 |
| 0-5 | 61 (57.5) |
| 6-10 | 13 (12.3) |
| ≥10 | 32 (30.2) |
| ≥1 Anticonvulsants at time of LITT, No./total No. (%) | 126/145 (86.9) |
| ≥1 Anticonvulsant stopped after LITT, No./total No. (%) | 35/126 (27.8) |
| Pediatric cohort age <22 y, No./total No. (%) | 14/145 (9.7) |
| No. of ablated areas, median (range) | 1 (1-2) |
| Blood loss, mean (SD), mL | 19.9 (17.6) |
| Length of hospital stay, median (IQR), h | 45.1 (30.5-77.7) |
| Ablation volume, mean (SD), mL | 31.7 (16.8) |
| Length of surgery, mean (SD), h | 4.03 (1.74) |
| ICU | 12 (85.7) |
| ICU time, median (IQR), d | 23.3 (17.8-45.6) |
| Discharged to home | 14 (100) |
| Completed 2-y follow-up visit | 6 (42.9) |
| Engel 1 outcomes, No./total No. (%) | |
| 1 y | 4/11 (36.4) |
| 2 y | 3/6 (50) |
| ILAE 1/2 outcomes, No./total No. (%) | |
| 1 y | 5/11 (45.5) |
| 2 y | 4/6 (66.7) |
| QOLIE total score improvement at 2 y, median (IQR) | 44.1 (7.7-80.2) |
Abbreviations: DNET, dysembryoplastic neuroepithelial tumor; ICU, intensive care unit; ILAE, International League Against Epilepsy; LITT, laser interstitial thermal therapy; QOLIE-31, 31-Item Quality of Life in Epilepsy Inventory.
Race and ethnicity data were collected via patient self-report and reported because we sought to understand if there were racial or ethnic differences in mesial temporal lobe epilepsy LITT outcomes.
Other race included Asian, multiple races, and unknown, consolidated for patient privacy.
Procedural Outcomes
The mean (SD) ablation volume was 28.2 (29.8) mL, the mean (SD) surgery length was 4.33 (2.1) hours. A variety of navigation systems were used, primarily either the ROSA Brain System (n = 50) (Zimmer Biomet) or ClearPoint Navigation (n = 32) (ClearPoint Neuro). Shorter mean (SD) skin-to-skin times were seen with the ROSA Brain System relative to ClearPoint Navigation (215.3 [91.7] minutes vs 352.6 [142.3] minutes, respectively; P = <.001). Mean (SD) blood loss was 22.0 (23.1) mL. The median (IQR) length of stay was 31.2 (28.9-55.5) hours or 1.3 (1.2-2.3) days with further description of outcomes shown in Table 2. A median (IQR) of 0.92 (0.8-1.2) days was spent in the intensive care unit (ICU), with 110 (76.9%) admitted to the ICU following surgery. Nearly all patients (n = 140 [96.6%]) were discharged home. The mean (SD) discharge head pain score on a scale from 0 to 10 was 2.1 (2.6), higher than baseline head pain scores (mean [SD], 1.0 [1.9]) (P < .001). The highest postsurgical head pain score was at 1 month post-LITT (mean [SD], 1.2 [2.1]), not different from baseline. Readmission within 90 days occurred in 11 patients (7.7%), commonly for seizures.
Table 2. Procedural Outcomes.
| Outcome | Participants (N = 145) |
|---|---|
| Engel 1 at 1 y, No./total No. (%) | 63/104 (60.6) |
| Engel 1 at 2 y, No./total No. (%) | 45/77 (58.4) |
| ILAE 1/2 at 1 y, No./total No. (%) | 58/104 (55.8) |
| ILAE 1/2 at 2 y, No./total No. (%) | 44/77 (57.2) |
| No. of lesions/areas ablated during procedure, median (range) | 1 (1-3) |
| Blood loss, mean (SD), mL | 22.0 (23.1) |
| Ablation volume, mean (SD), mL | 28.2 (29.8) |
| Length of surgery, median (IQR; range), h | 3.79 (2.83-5.45; 0.9-11.03) |
| Length of surgery, mean (SD), h | 4.33 (2.1) |
| ICU, No./total No. (%) | 110/143 (76.9) |
| ICU time, median (IQR), d | 0.92 (0.8-1.2) |
| Length of hospital stay, median (IQR), h | 31.2 (28.9-55.5) |
| Discharged to home, No. (%) | 140 (96.6) |
| Discharge head pain score (0-10), mean (SD) | 2.1 (2.6) |
Abbreviations: ICU, intensive care unit; ILAE, International League Against Epilepsy.
Seizure and ASM Outcomes
Median (IQR) follow-up time was 2.33 (1.50-3.46) years. Figure 126 displays longitudinal seizure outcomes by Engel and ILAE outcomes. Pertinently, 77 patients reached 2-year follow-up, 45 (58.4%) and 44 (57.2%) of whom had Engel 1 or ILAE 1/2 outcomes, respectively. Longitudinal LAANTERN outcomes show relative stability for both ILAE and Engel outcomes. LAANTERN outcomes were also compared to a historical control from the 2001 randomized clinical trial for ATL (eTables 2A and 2B in Supplement 1), where 3 of 40 patients (8%) in the medical management arm achieved Engel 1 outcome and 23 of 40 (58%) achieved Engel 1 outcome 1-year follow-up.26 When comparing LAANTERN outcomes at 1-year follow-up (63 of 105 Engel 1 outcome) to the medical management historical control, patients in LAANTERN had an odds ratio (OR) of 18.5 (95% CI, 5.6-59.5) of achieving Engel 1 outcome.26
Figure 1. Post–Laser Interstitial Thermal Therapy Seizure Outcome Data.
ILAE indicates International League Against Epilepsy.
aWiebe et al.26
We examined post hoc whether auras, FBTC semiology, race, ethnicity, MTS, ablation volume, or drug resistance for 6 years or longer were associated with seizure outcomes at 1 and 2 years (eTables 3-5 in Supplement 1). No factor studied in our post hoc review was associated with outcome. More granularly, auras had no association with 2-year outcomes for either Engel 1 or ILAE 1/2, but approached positive predictivity for Engel 1 outcome (OR, 2.37; 95% CI, 0.77-7.28; P = .08) at 1 year. Similarly, MTS was not associated with outcome at 2 years for either Engel 1 or ILAE 1/2, but approached positive predictivity for an ILAE 1/2 outcome (OR, 2.27; 95% CI, 0.86-5.99; P = .10) at 1 year. FBTC approached negative predictivity at 2-year follow-up for both Engel 1 (OR, 0.29; 95% CI, 0.08-1.05; P = .06) and ILAE 1/2 outcomes (OR, 0.31; 95% CI, 0.08-1.16; P = .08).
By 24 months post-LITT, 44 of 126 patients (34.9%) either stopped or reduced their ASM dose. There were similar outcomes between patients who altered or did not alter their ASM dose (eTable 6 in Supplement 1).
There was 1 probable and 1 possible sudden unexpected death in epilepsy (SUDEP) from a total of 365.22 person-years at risk. The estimated SUDEP incidence was 5.48 (95% CI, 1.38-21.8) per 1000 person-years.
AEs
There were 26 AEs in 24 patients. These AEs were adjudicated as 11 mild, 12 moderate, and 3 severe (Table 3). Permanent changes from AEs were seen in 8 patients (5.5%). The most common mild AE was a clinically insignificant intracranial hemorrhage (n = 4) while the most common moderate AE was increased seizure frequency/duration or severity (n = 6).
Table 3. Adverse Events.
| Adverse event | Participants, No. (%) (N = 145) |
|---|---|
| Participants with adverse events, No./total No. (%) | 24/145 (16.5) |
| Total No. of adverse events | 26 |
| Events considered transient/temporary | 18/26 |
| Adverse event defined as a neurological deficit, No./total No. (%) | 3/145 (2.07) |
| Blurry vision/visual disturbance/visual field deficit | 1 (0.7) |
| Loss of touch, pain, or proprioception | 1 (0.7) |
| Speech | 1 (0.7) |
| Seizures: increased frequency/duration/severity | 6 (4.1) |
| Intracranial hemorrhage: clinically insignificant | 4 (2.8) |
| Pulmonary embolism or other air embolism | 2 (1.4) |
| Adverse drug reaction | 1 (0.7) |
| Cerebral infarction | 1 (0.7) |
| Mood changes (eg, depression) | 1 (0.7) |
| Corneal abrasion | 1 (0.7) |
| DVT | 1 (0.7) |
| Cerebral edema: worsening symptomatic | 1 (0.7) |
| Electrolyte imbalance/hyponatremia | 1 (0.7) |
| Hypertension | 1 (0.7) |
| Meningitis | 1 (0.7) |
| Pneumonia | 1 (0.7) |
| Urinary retention | 1 (0.7) |
Abbreviation: DVT, deep vein thrombosis.
The first severe AE was a pulmonary embolism (PE) noted immediately postoperatively. Due to PE severity and medical instability, the patient underwent emergent sternotomy for a successful open pulmonary thrombectomy. However, the patient died 6 days later of multiorgan failure. The second severe AE was a patient with postoperative bilateral middle cerebral artery infarctions and a PE found 24 hours following the LITT procedure, with evaluation later finding a patent foramen ovale. At last follow-up, the patient reported ongoing weakness and aphasia. The third patient had bilateral PEs immediately postoperatively. The patient received intravenous tissue plasminogen activator with PE resolution. However, this caused intraparenchymal, intraventricular, and subarachnoid hemorrhages necessitating extraventricular drain placement. There was prolonged encephalopathy that resolved without focal neurological deficits. At last follow-up, a walker was used for deconditioning, but no other focal neurological deficits were observed. The safety committee ruled these severe AEs were events that can occur during general brain surgery rather than being specifically related to LITT. All severe cases were above the upper quartile of case times and used the same navigation system.
QOL Outcomes
Outcomes for QOLIE-31 are shown in Figure 2. Nearly all time frames noted QOL improvements except year 5 (which only 11 patients reached). Nearly all subdomains showed improvement except for emotional well-being, which neither improved nor worsened. The seizure worry, medication effects, and social functioning subdomains had notable improvements.
Figure 2. Median 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) Scores Post–Laser Interstitial Thermal Therapy.
Patients with Engel 1 or ILAE 1/2 outcomes had improved QOLIE-31 scores at 1- and 2-year follow-up compared to Engel 2-4 and ILAE 3-6, respectively, as well as most subdomains. No QOLIE-31 outcome difference at 1 year was noted when stratifying outcomes by Black vs non-Black race, although Black race trended toward less improved seizure worry (mean [SD], 5.25 [19.45] in Black patients vs 23.27 [29.97] in non-Black patients; P = .10). Differences were limited by having 8 Black patients reach 1-year follow-up. Conversely, Hispanic patients showed QOLIE-31 improvement at 1-year follow-up (26.17 [26.71] for Hispanic patients vs 7.82 [21.64] for non-Hispanic patients; P = .04) compared to non-Hispanic patients, driven by energy/fatigue and social functioning improvements and nonsignificant improvements in emotional well-being and cognitive functioning. When dichotomizing QOLIE-31 outcomes based on DRE length, patients with DRE longer than 6 years had better QOLIE-31 outcomes overall, driven by cognitive functioning and energy/fatigue improvements.
Pediatric Subcohort
Fourteen pediatric patients underwent MTLE LITT. Procedural outcomes are noted in Table 1. Six patients reached 2-year follow-up, 3 of whom (50%) were Engel 1 and 3 (60%) ILAE 1/2, not different from the adult cohort. Those 6 patients did not show QOLIE-31 improvements, but did show numeric improvement in seizure worry, medication effect, and social functioning scores.
Practice Effect and Longitudinal Care Changes
Improved LITT outcomes with increased neurosurgeon LITT familiarity has been previously considered.12,27 To assess, we stratified outcomes of the first 4 years vs the last 4 years of LAANTERN (eTable 7 in Supplement 1). No difference in seizure outcome was seen. For longitudinal care changes, only an 18.5% decrease in postprocedure ICU care in the latter portion of the study was seen (cases from 2020 to 2023) (51 of 58 [87.9%] vs 59 of 85 [69.4%]; P = .01) whereas increased trajectories (mean [SD], 1.2 [0.5] vs 1.4 [0.6]; P = .08) were not significant in the latter portion of the study.
Discussion
Data from this cohort study provide evidence for LITT as an effective and safe option for drug-resistant MTLE. Of 77 patients reaching 2-year follow-up, 45 of 77 (58.4%) and 44 of 77 (57.2%) reached Engel 1 and ILAE 1/2 outcomes, respectively. These outcomes are similar to the 2001 MTLE randomized clinical trial for ATL26 as well as previous retrospective multicenter LITT studies.7,15 LAANTERN outcomes provide evidence of LITT utility for drug-resistant MTLE compared to medical therapy alone.26 The 18.5 OR of Engel 1 outcome compared to medical management historical control is sufficiently large to likely exclude confounding or other biases related to use of historical controls. The SUDEP rate in our study of 5.48 per 1000 person-years is numerically lower than previously reported post-LITT SUDEP rates (8.0 per 1000 person-years),28 but remains higher than resective surgery.29,30 Our longitudinal data revealed that postoperative ICU admissions are decreasing for patients undergoing LITT over time, suggesting improved familiarity and physician comfort for the safety of the postoperative course. Thus, it is reasonable for a physician to postoperatively monitor a patient in the ICU or on the floor depending on each patient’s individual circumstances.
As stated previously, no factor studied in our post hoc was associated with outcome. Still, 3 of these factors bear some discussion. FBTC semiology trended toward a negative association while auras and MTS trended toward association with favorable outcomes. FBTC semiology has previously predicted negative surgical outcomes,31,32,33 so our results provide LITT-specific data in line with, although not confirmatory of, those findings. Our data provide perspective on the association of MTS with surgical outcome. In line with other multicenter studies,7,34 our data indicate MTS is not associated with long-term outcomes. However, our data do suggest that MTS may portend good short-term (ie, 1-year) seizure outcomes. The outcome differences at 1- and 2-year follow-up may explain outcome variability for MTS reported by previous single-center studies.8,9,10,11,12,16,27 Our aura outcome possible association is in line with some research suggesting a lack of predictive value for auras35,36 while other studies indicate predictivity specifically by aura type.37,38,39
LAANTERN adds to the pediatric LITT literature. A recent pediatric LITT review reviewed 179 patients. Only 64 had nonhypothalamic hamartoma LITT, 7 specifically for MTS.40 The inclusion of 14 pediatric patients in our study increases the overall number, specifically for pediatric MTLE LITT outcomes. The 6 pediatric patients with 2-year follow-up had similar outcomes as adults, although the small patient number limits the observation. Similarly, lack of QOLIE-31 score improvements is not reliable, as only 3 patients had 2-year QOLIE-31 data. Still, those 3 patients showed numerical improvements in seizure worry, medication effect, and social functioning scores.
These results continue to support LITT as an expedient surgery with short length of stay, low readmission rates, and minimal head pain scores at discharge, particularly compared to open resection.4 The median length of stay was 1.3 days, favorably comparing to 3 days for resection.1 The 30-day readmission rate of 7.7% compares favorably to the 11% rate for ATL.41 Moreover, LAANTERN’s longitudinal design allowed the observation that post-LITT ICU time has decreased. The overall AE rate in the LAANTERN cohort (16.5%) was comparable to the reported AE rate for patients undergoing ATL as well as MTLE LITT, although LAANTERN permanent deficits (5.5%) are lower than ATL.1,5 As such, patients should be counseled regarding LITT as a neurosurgical procedure with associated risks, even though it is minimally invasive. Notably, the 3 serious AEs as well as 1 moderate AE in this cohort were related to venous thromboembolism. Patients undergoing LITT are manipulated and moved less compared to patients undergoing resection. It is hypothesized that decreased movement could raise the risk of thromboembolism. To minimize risks, regular intraoperative movement of the lower extremities, appropriate patient padding, and sequential compression devices may decrease risk. Surgical time difference between navigation systems with potentially prolonged surgeries could also influence thromboembolism risk.
The proportion of Black and Hispanic patients in our study (9.0% and 12.5%, respectively) was lower than the 2023 US Census data (13.6% and 19.1%, respectively).42 As epilepsy incidence does not differ by race,43 epilepsy incidence rates should reasonably mirror census data. Thus, our data suggest that efforts should continue to expand epilepsy surgery access and epilepsy research involvement to Black and Hispanic communities to provide data that are better generalizable to the population as a whole.
Longitudinal QOL data are an important addition to understanding postoperative LITT outcomes. Adding the 145 patients undergoing LITT for MTLE in this study to the 10 patients undergoing LITT previously reported is sizable and important for establishing MTLE LITT QOL benefits. These data show overall QOLIE-31 improvements and also in nearly all subdomains through almost all follow-up data points, similar to findings of a seminal prospective multicenter study for resective epilepsy surgery QOL outcomes.44 More specifically, LAANTERN’s own QOL improvements are in line with those reported by patients who underwent ATL for DRE, with Engel 1 outcome patients also more likely to also have QOL improvements.18,45,46,47,48 Thus, patients with MTLE undergoing LITT may be reasonably counseled for positive QOL outcomes that are in line with ATL when a seizure-free outcome is realized. The QOLIE-31 differences for Black and Hispanic patients warrant further research, as LAANTERN was not designed to detect causes of QOLIE-31 changes in those groups. Lastly, it was surprising that patients with more than 6 years of DRE had higher QOLIE improvement scores. This could be explained by patients with longer-term DRE having more time for worsened quality of life, patients with shorter-term DRE not having enough time to note chronic QOL concerns, or a combination of both factors.
Strengths and Limitations
The LAANTERN study has strengths and limitations. Strengths include the study’s prospective multicenter design. This is balanced by the lack of a nonsurgical comparator group. Still, LAANTERN’s 18.5 OR of a Engel 1 outcome compared to a medical management historical control minimizes this limitation.26,49 Other strengths include active monitoring and source verification of data input by centers as well as AE adjudication by an independent safety review committee outside of each center. This stringent monitoring allowed for a wider variety of recognized AEs, particularly transient AEs. Lastly, long-term follow-up among these patients for up to 5 years is a study strength, although only 11 patients reached 5-year follow-up. The lack of accompanying neuropsychological data in a MTLE study is a limitation, as cognitive risk is a main concern for any mesial temporal lobe surgery. Additionally, as postoperative cognitive changes, particularly in patients who are not seizure free, can affect QOL,48 accompanying neuropsychological data would have allowed greater exploration of the QOL outcomes in this study. Similarly, visual field data would have been additive to existing literature.50 A companion study (Patient Neuropsychological Outcomes After Laser Ablation [PENSAR]; NCT05075850) was started during LAANTERN to remedy these weaknesses.
Conclusions
We report outcomes for what is, to our knowledge, the largest prospective MTLE LITT cohort. These multicenter data provide evidence for positive seizure outcomes following MTLE LITT, particularly when compared to a medical management historical control in addition to QOL improvements that allow for increased generalizability of MTLE LITT utility. Relative to neuromodulation, MTLE LITT outcomes are measurably improved and better approximate ATL effectiveness.5,51,52 The 14 pediatric patients bolster existing pediatric LITT data. While AEs occurred, most were mild or transient. Low postoperative pain scores, low readmission rates, and shorter length of stays indicate a well-tolerated procedure with decreased ICU admission more common as the study progressed. LAANTERN data support LITT as an effective and safe treatment option for drug-resistant MTLE.
eTable 1. Presurgical Testing in Addition to MRI and EEG
eTable 2. A, Wiebe et al. 2001 Historical Control Comparison. Medical Management Cohort. B, Weibe et al. 2001 Historical Control Comparison. Surgical Cohort
eTable 3. Multivariable Logistic Regression for Engel 1 compared to Engel 2-4 at 1 and 2 Years
eTable 4. Multivariable Logistic Regression for ILAE 1/2 compared to ILAE3-6 at 1 and 2 Years
eTable 5. Variable Prediction of Engel 1 and ILAE 1-2 Classification at 1 Year
eTable 6. Anticonvulsant Use Over Time
eTable 7. Longitudinal Practice Effect
Data sharing statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable 1. Presurgical Testing in Addition to MRI and EEG
eTable 2. A, Wiebe et al. 2001 Historical Control Comparison. Medical Management Cohort. B, Weibe et al. 2001 Historical Control Comparison. Surgical Cohort
eTable 3. Multivariable Logistic Regression for Engel 1 compared to Engel 2-4 at 1 and 2 Years
eTable 4. Multivariable Logistic Regression for ILAE 1/2 compared to ILAE3-6 at 1 and 2 Years
eTable 5. Variable Prediction of Engel 1 and ILAE 1-2 Classification at 1 Year
eTable 6. Anticonvulsant Use Over Time
eTable 7. Longitudinal Practice Effect
Data sharing statement
