Shifts in epilepsy treatment: a 12-year review of surgical approaches and outcomes in lesional and nonlesional epilepsy

J Neurosurg 144:259–272, 2026

This study analyzes national inpatient trends from 2009–2020 comparing lesional and nonlesional epilepsy patients who underwent surgical or neuromodulation treatments. Using NIS data with propensity score matching, it reports demographic differences, socioeconomic disparities, and shifting utilization patterns across VNS, RNS, DBS, resection, radiosurgery, and LITT.

The findings reveal increasing adoption of RNS and LITT, declining VNS and radiosurgery, higher costs for most interventions, and shorter length of stay with LITT. Persistent racial and income-based inequities in access and differing outcomes by lesion status prompt calls for tailored care and further cost-effectiveness and long-term outcome studies.

Distinct Patient Profiles: Lesional epilepsy patients are older, more likely male, have higher comorbidity burdens, and higher income/Medicare coverage compared to nonlesional epilepsy patients, who are more prevalent in lower income quartiles and rely more on Medicaid or private insurance.

Surgical Treatment Trends: Use of responsive neurostimulation (RNS) and laser interstitial thermal therapy (LITT) increased significantly for both lesional and nonlesional epilepsy from 2009–2020, while vagus nerve stimulation (VNS) declined for nonlesional epilepsy; deep brain stimulation (DBS) and radiosurgery declined for both groups.

Resective Surgery Patterns: Resective surgery utilization increased significantly for nonlesional epilepsy, but not for lesional epilepsy, indicating a growing acceptance of surgery in nonlesional cases despite the absence of overt lesions.

Healthcare Disparities: White patients, and those in higher income quartiles, have higher probabilities of receiving advanced treatments (VNS, RNS, DBS, resective surgery, radiosurgery); Black patients have persistently lower access regardless of income, and Hispanic patients show variable, income-dependent access.

Outcomes by Modality: RNS and LITT are associated with shorter or unchanged length of stay (LOS) and higher likelihood of routine discharge, while DBS and resective surgery increase LOS and costs; all surgical interventions increase hospital charges.

LITT Advantages: LITT is linked to decreased LOS and improved routine discharge rates, especially for lesional epilepsy, but incurs higher total charges compared to other modalities.

Mortality Impact: None of the interventions (VNS, RNS, DBS, resective surgery, radiosurgery, LITT) significantly affected mortality in either lesional or nonlesional epilepsy groups.

Need for Tailored Approaches: Persistent demographic, socioeconomic, and clinical differences between lesional and nonlesional epilepsy patients highlight the importance of individualized treatment strategies and further research on long-term and cost-effectiveness outcomes.

Laser interstitial thermal therapy for high-grade glioma: a systematic review, meta-analysis, and meta-regression

Neurosurg Focus 59(2):E10, 2025

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for high-grade glioma (HGG) showing mean overall survival of 11.7 months and progression-free survival of 5.3 months. LITT offers acceptable safety, especially for deep or unresectable tumors, but further randomized studies are needed to confirm long-term efficacy.

• Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for high-grade glioma (HGG), especially in deep-seated or unresectable tumors.

• A systematic review and meta-analysis of 21 studies including 602 patients found mean overall survival (OS) after LITT was 11.74 months and mean progression-free survival (PFS) was 5.3 months.

• 6-, 12-, and 24-month OS rates were 77.0%, 48.9%, and 16.1%; PFS rates were 37.1%, 12.8%, and 4.3%, respectively.

• Permanent postoperative deficits occurred in 5.7% of patients, with higher rates in newly diagnosed HGG than recurrent cases (4.15% vs 0.02%).

• Tumor progression after LITT was observed in about 80% of patients, and overall mortality was 67.7%.

• Deep/unresectable tumors and IDH-wildtype mutations were associated with worse outcomes; smaller tumor size and higher baseline KPS predicted better survival.

• LITT showed acceptable safety and feasibility, but randomized prospective studies are needed to confirm long-term efficacy.

• Common complications included hemiparesis, weakness, and temporary neurological deficits.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines Update for the Role of Emerging Therapies in the Management of Patients With Metastatic Brain Tumors

Neurosurgery 96:1172–1177, 2025

This 2025 CNS guideline update reviews evidence for emerging therapies in adult brain metastases, providing new recommendations on targeted therapies, immunotherapy, radiosensitizers, and laser interstitial thermal therapy, while noting insufficient evidence for some modalities. Recommendations aim to guide multidisciplinary management beyond standard surgical and radiation treatments.

• This guideline is an updated systematic review on emerging therapies for adult patients with metastatic brain tumors (MBTs), focusing on evidence-based recommendations.

• Targeted therapies and immunotherapies have the strongest new evidence, especially for NSCLC, melanoma, and breast cancer brain metastases.

• Level I recommendations include the use of specific agents such as icotinib with WBRT for EGFR-mutant NSCLC, alectinib for ALK-positive NSCLC, and dabrafenib plus trametinib for BRAFV600E-positive melanoma.

• Immune checkpoint inhibitors (e.g., ipilimumab plus nivolumab for melanoma, ICIs for NSCLC) are recommended to improve survival and intracranial control in selected patients.

• Laser interstitial thermal therapy (LITT) may be considered equivalent to craniotomy or medical management in certain cases of tumor progression or radiation necrosis after SRS.

• There is insufficient evidence to recommend interstitial modalities or high-intensity focused ultrasound (HIFU) for brain metastases.

• Future research should prioritize prospective, comparative studies for modalities like LITT and HIFU, and the guideline will be updated as new evidence emerges.

• Clinical decisions should be individualized, and participation in clinical trials is encouraged to refine treatment strategies for MBTs.

Risk of Tract Seeding Following Laser Interstitial Thermal Therapy for Brain Tumors

Neurosurgery 93:198–205, 2023

The management of intracranial oncological disease remains a significant challenge despite advances in systemic cancer therapy. Laser interstitial thermal therapy (LITT) represents a novel treatment for local control of brain tumors through photocoagulation with a stereotactically implanted laser fiber. Because the use of laser interstitial thermal therapy continues to increase within neurosurgery, characterization of LITT is necessary to improve outcomes.

OBJECTIVE: To quantify the risk of tumor seeding along the laser fiber tract in patients receiving LITT for primary or metastatic brain tumors at a high-volume treatment center.

METHODS: We retrospectively reviewed all patients receiving LITT from 2015 to 2021 at our medical center. Patients with biopsy-confirmed tumors were included in this study. Tract seeding was identified as discontinuous, newly enhancing tumor along the LITT tract.

RESULTS: Fifty-six patients received LITT for biopsy-confirmed tumors from 2015 to 2021, with tract seeding identified in 3 (5.4%). Twenty-nine (51.8%) patients had gliomas, while the remainder had metastases, of which lung was the most common histology (20 patients, 74%). Tract seeding was associated with ablation proceeding inward from superficial tumor margin closest to the cranial entry point (P = .03). Patients with tract seeding had a shorter median time to progression of 1.1 (0.1-1.3) months vs 4.2 (2.2-8.6) months (P = .03).

CONCLUSION: Although the risk of tract seeding after LITT is reassuringly low, it is associated with decreased progression-free survival. This risk may be related to surgical technique or experience. Follow-up radiosurgery to the LITT tract has the potential to prevent this complication.

Laser interstitial thermal therapy using the Leksell Stereotactic System and a diagnostic MRI suite

Acta Neurochirurgica (2023) 165:549–554

Laser interstitial thermal therapy (LITT) is a stereotactic neurosurgical procedure used to treat neoplastic and epileptogenic lesions in the brain. A variety of advanced technological instruments such as frameless navigation systems, robotics, and intraoperative MRI are often described in this context, although the surgical procedure can also be performed using a standard stereotactic setup and a diagnostic MRI suite.

Methods We report on our experience and a surgical technique using a Leksell stereotactic frame and a diagnostic MRI suite to perform LITT.

Conclusion LITT can be safely performed using the Leksell frame and a diagnostic MRI suite, making the technique available even to neuro-oncology centers without advanced technological setup.

Acute Postoperative Seizures and Engel Class Outcome at 1 Year Postselective Laser Amygdalohippocampal Ablation for Mesial Temporal Lobe Epilepsy

Neurosurgery 91:347–354, 2022

MRI-guided laser interstitial thermal therapy (MRgLITT) for mesial temporal lobe epilepsy is a safe, minimally invasive alternative to traditional surgical approaches. Prognostic factors associated with efficacy are debated; preoperative epilepsy duration and semiology seem to be important variables.

OBJECTIVE: To determine whether acute postoperative seizure (APOS) after MRgLITT for mesial temporal lobe epilepsy is associated with seizure freedom/Engel class outcome at 1 year.

METHODS: A single-institution retrospective study including adults undergoing first time MRgLITT for mesial temporal lobe epilepsy (2010-2019) with ≥1-year follow-up. Preoperative data included sex, epilepsy duration, number of antiepileptics attempted, weekly seizure frequency, seizure semiology, and radiographically verified anatomic lesion at seizure focus. Postoperative data included clinical detection of APOS within 7 days postoperatively, and immediate amygdala, hippocampal, entorhinal, and parahippocampal residual volumes determined using quantitative imaging postprocessing. Primary outcome was seizure freedom/Engel classification 1 year postoperatively.

RESULTS: Of 116 patients, 53%(n = 61) were female, with an average epilepsy duration of 21 (±14) years, average 6 failed antiepileptics (±3), and weekly seizure frequency of 5. APOS was associated with worse Engel class (P = .010), conferring 6.3 times greater odds of having no improvement vs achieving seizure freedom at 1 year. Residual amygdala, hippocampal, entorhinal, and parahippocampal volumes were not statistically significant prognostic factors.

CONCLUSION: APOS was associated with a lower chance of seizure freedom at 1 year post-MRgLITT for mesial temporal lobe epilepsy. Amygdala, hippocampal, entorhinal, and parahippocampal residual volumes after ablation were not significant prognostic factors.

 

Risk of tract recurrence with stereotactic biopsy of brain metastases

J Neurosurg 136:1045–1051, 2022

Stereotactic biopsy is increasingly performed on brain metastases (BrMs) as improving cancer outcomes drive aggressive multimodality treatment, including laser interstitial thermal therapy (LITT). However, the tract recurrence (TR) risk is poorly defined in an era defined by focused-irradiation paradigms. As such, the authors aimed to define indications and adjuvant therapies for this procedure and evaluate the BrM-biopsy TR rate.

METHODS In a single-center retrospective review, the authors identified stereotactic BrM biopsies performed from 2002 to 2020. Surgical indications, radiographic characteristics, stereotactic planning, dosimetry, pre- and postoperative CNS-directed and systemic treatments, and clinical courses were collected. Recurrence was evaluated using RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria.

RESULTS In total, 499 patients underwent stereotactic intracranial biopsy for any diagnosis, of whom 25 patients (5.0%) underwent biopsy for pathologically confirmed viable BrM, a proportion that increased over the time period studied. Twelve of the 25 BrM patients had ≥ 3 months of radiographic follow-up, of whom 6 patients (50%) developed new metastatic growth along the tract at a median of 5.0 months post-biopsy (range 2.3–17.1 months). All of the TR cases had undergone pre- or early post-biopsy stereotactic radiosurgery (SRS), and 3 had also undergone LITT at the time of initial biopsy. TRs were treated with resection, reirradiation, or observation/systemic therapy.

CONCLUSIONS In this study the authors identified a nontrivial, higher than previously described rate of BrM-biopsy tract recurrence, which often required additional surgery or radiation and justified close radiographic surveillance. As BrMs are commonly treated with SRS limited to enhancing tumor margins, consideration should be made, in cases lacking CNS-active systemic treatments, to include biopsy tracts in adjuvant radiation plans where feasible.

Extent of parahippocampal ablation is associated with seizure freedom after laser amygdalohippocampotomy

J Neurosurg 135:1742–1751, 2021

The authors aimed to examine the relationship between mesial temporal subregion ablation volume and seizure outcome in a diverse cohort of patients who underwent stereotactic laser amygdalohippocampotomy (SLAH) for mesial temporal lobe epilepsy (MTLE).

METHODS Seizure outcomes and pre- and postoperative images were retrospectively reviewed in patients with MTLE who underwent SLAH at a single institution. Mesial temporal subregions and the contrast-enhancing ablation volume were manually segmented. Pre- and postoperative MR images were coregistered to assess anatomical ablation. Postoperative MRI and ablation volumes were also spatially normalized, enabling the assessment of seizure outcome with heat maps.

RESULTS Twenty-eight patients with MTLE underwent SLAH, 15 of whom had mesial temporal sclerosis (MTS). The rate of Engel class I outcome at 1 year after SLAH was 39% overall: 47% in patients with MTS and 31% in patients without MTS. The percentage of parahippocampal gyrus (PHG) ablated was higher in patients with an Engel class I outcome (40% vs 25%, p = 0.04). Subregion analysis revealed that extent of ablation in the parahippocampal cortex (35% vs 19%, p = 0.03) and angular bundle (64% vs 43%, p = 0.02) was positively associated with Engel class I outcome. The degree of amygdalohippocampal complex (AHC) ablated was not associated with seizure outcome (p = 0.30).

CONCLUSIONS Although the AHC was the described target of SLAH, seizure outcome in this cohort was associated with degree of ablation for the PHG, not the AHC. Complete coverage of both the AHC and PHG is technically challenging, and more work is needed to optimize seizure outcome after SLAH.

Magnetic Resonance Imaging-Guided Stereotactic Laser Ablation of Deep Cerebral Cavernous Malformations

Neurosurgery 89:635–644, 2021

Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRgLITT) has been used successfully to treat epileptogenic cortical cerebral cavernous malformations (CCM). It is unclear whether MRgLITT would be as feasible or safe for deep CCMs

OBJECTIVE: To describe our experience with MRgLITT for symptomatic deep CCMs

METHODS: Patients’records were reviewed retrospectively. MRgLITT was carried out using a commercially available system in an interventional MRI suite with efforts to protect adjacent brain structures. Immediate postoperative imaging was used to judge ablation adequacy. Delayed postoperative MRI was used to measure lesion volume changes during follow-up.

RESULTS: Four patients with CCM in the thalamus, putamen, midbrain, or subthalamus presented with persistent and disabling neurological symptoms. A total of 2 patients presented with disabling headaches and sensory disturbances and 2 with recurrent symptomatic hemorrhages, of which 1 had familial CCM. Patients were considered by vascular neurosurgeons to be poor candidates for open surgery or had refused it. Multiple trajectories were used in most cases. Adverse events included device malfunction with leakage of saline causing transient mass effect in one patient, and asymptomatic tract hemorrhage in another. One patient suffered an expected mild but persistent exacerbation of baseline deficits. All patients showed improvement from a previously aggressive clinical course with lesion volume decreased by 20% to 73% in follow-up.

CONCLUSION: MRgLITT is feasible in the treatment of symptomatic deep CCM but may carry a high risk of complications without the benefit of definitive resection. We recommend cautious patient selection, low laser power settings, and conservative temper- ature monitoring in surrounding brain parenchyma.

MRI-guided stereotactic laser corpus callosotomy for epilepsy

J Neurosurg 135:770–782, 2021

Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames.

METHODS The authors retrospectively reviewed sequential adult epilepsy surgery patients who underwent SLCC procedures at a single institution. They describe workflows, stereotactic errors, percentage disconnection, hospitalization durations, adverse events, and seizure outcomes after performing anterior, posterior, and complete SLCC procedures using a frameless stereotactic surgical robot versus direct MRI guidance platforms.

RESULTS Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20–49 years), the median duration of epilepsy was 21 years (range 9–48 years), and median postablation follow-up was 20 months (range 4–44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%–80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm (range 0.2–2.0 mm) versus 2.4 mm (range 0.6–6.1 mm; p = 0.0011). The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique.

CONCLUSIONS This is the largest reported series of SLCC for epilepsy to date. SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC. Methodological advancements and larger studies are needed.

Corpus callosotomy performed with laser interstitial thermal therapy

J Neurosurg 134:314–322, 2021

Corpus callosotomy is a palliative procedure that is effective at reducing seizure burden in patients with medically refractory epilepsy. The procedure is traditionally performed via open craniotomy with interhemispheric microdissection to divide the corpus callosum. Concerns for morbidity associated with craniotomy can be a deterrent to patients, families, and referring physicians for surgical treatment of epilepsy. Laser interstitial thermal therapy (LITT) is a less invasive procedure that has been widely adopted in neurosurgery for the treatment of tumors. In this study, the authors investigated LITT as a less invasive approach for corpus callosotomy.

METHODS The authors retrospectively reviewed all patients treated for medically refractory epilepsy by corpus callosotomy, either partial or completion, with LITT. Chart records were analyzed to summarize procedural metrics, length of stay, adverse events, seizure outcomes, and time to follow-up. In select cases, resting-state functional MRI was performed to qualitatively support effective functional disconnection of the cerebral hemispheres.

RESULTS Ten patients underwent 11 LITT procedures. Five patients received an anterior two-thirds LITT callosotomy as their first procedure. One patient returned after LITT partial callosotomy for completion of callosotomy by LITT. The median hospital stay was 2 days (IQR 1.5–3 days), and the mean follow-up time was 1.0 year (range 1 month to 2.86 years). Functional outcomes are similar to those of open callosotomy, with the greatest effect in patients with a significant component of drop attacks in their seizure semiology. One patient achieved an Engel class II outcome after anterior two-thirds callosotomy resulting in only rare seizures at the 18-month follow-up. Four others were in Engel class III and 5 were Engel class IV. Hemorrhage occurred in 1 patient at the time of removal of the laser fiber, which was placed through the bone flap of a prior open partial callosotomy.

CONCLUSIONS LITT appears to be a safe and effective means for performing corpus callosotomy. Additional data are needed to confirm equipoise between open craniotomy and LITT for corpus callosotomy.

Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma

 

NeuroBlate

J Neurosurg 118:1202–1219, 2013

Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose–escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).

Methods. Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, sidefiring laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation.

Results. Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals–Case Medical Center). Their average age was 55 years (range 34–69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70–90). The mean tumor volume was 6.8 ± 5 cm3 (range 2.6–19 cm3), the percentage of tumor treated was 78% ± 12% (range 57%–90%), and the conformality index was 1.21 ± 0.33 (range 1.00–2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62–767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose.

Conclusions. NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. Clinical trial registration no.: NCT00747253 (ClinicalTrials. gov).