Turning Up the Heat on Temporal Lobe Epilepsy: LAANTERN Helps Illuminate the Role of Laser Ablation

Commentary

Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of drug-resistant epilepsy (DRE). Decades of clinical research—spanning case series, metaanalyses, and randomized controlled trials—have definitively proven that resective surgery is dramatically more likely to stop a person with DRE's seizures than continued medication.^1–3 In fact, the touchstone pivotal trial by Wiebe and colleagues, now 25 years old, is one of the select neurosurgical trials where mortality was exclusive to the nonsurgical group, due to sudden unexpected death in epilepsy. ¹

Despite this overwhelming evidence, surgical intervention for epilepsy remains remarkably underutilized. ⁴ While the reasons for this treatment gap are varied, a major contributing factor is the understandable fear of open brain surgery. People with epilepsy often prefer a safer, less invasive option, even if that option carries a slightly lower probability of absolute seizure freedom. ⁵ Consider a parallel in movement disorders: focused ultrasound is a newer, incisionless alternative to deep brain stimulation (DBS) for tremor, offering comparable efficacy but more frequent minor side effects. ⁶ Yet, patients overwhelmingly prefer focused ultrasound. ⁷ Any advancement that decreases surgical invasiveness while maintaining effectiveness will make more patients willing to consider a potentially curative, life-saving intervention.

Laser interstitial thermal therapy (LITT) might be one such therapy. It is minimally invasive, requiring only small stab incisions to place thin probes into the brain—markedly less invasive than a traditional craniotomy. Numerous studies have demonstrated that this translates to shorter hospital stays and lower morbidity compared to open surgery. ⁸

Once positioned, the laser probes heat and ablate the putative epileptic focus, most commonly the mesial temporal structures. These ablations are conceptually comparable to a selective amygdalohippocampectomy, but the volume of tissue ablated is constrained by thermal conductivity, nearby heat sinks (ventricles and blood vessels), and linear surgical trajectories. Because the hippocampus and amygdala are not linear, complete ablation is rarely accomplished. Typical ablation volumes are ∼30 mL, a little smaller than a ping pong ball. This raises a critical question: by reducing the volume of epileptogenic tissue removed, how much seizure freedom is sacrificed?

Until recently, existing data supporting LITT has been retrospective. Multicenter retrospective series have reported Engel 1 rates of 58% at 2 years. ⁹ This is comparable to the Wiebe randomized controlled trial (RCT), which demonstrated 58% seizure freedom at one year—but retrospective cohorts often outpace controlled trials, raising concerns that LITT outcomes might look less favorable under rigorous scrutiny.

The LAANTERN registry was designed to bridge this gap, providing prospectively collected outcomes data for laser ablation in MTLE. ¹⁰ Prospective trials reduce reporting and selection biases, standardize outcome measures, and better characterize patient attrition. While prospective registries still fall short of the evidentiary weight of an RCT, they remain superior to retrospective chart reviews.

The LAANTERN study enrolled 145 patients with MTLE who underwent laser ablation across 15 US centers. Roughly half (52.5%) had mesial temporal sclerosis, and the majority (72.1%) had failed four or more antiseizure medications.

Consistent with prior retrospective reports, hospital stays were notably short, and overall morbidity was low. The median length of stay was just one day, in contrast to the multiday stays typical of open resection. Adverse events were reported in 24 of the 145 patients (16.5%). Most of these were mild and transient, such as temporary increases in seizure frequency (4% of cases) or urinary tract infections. However, there were three severe adverse events, all related to venous thromboembolism (VTE), resulting in one patient death and another suffering permanent neurologic disability. The study authors attribute this to reduced patient mobilization, but the MRI environment may be equally contributory: MRI-compatible sequential compression devices are scarce, and many centers rely solely on static compression stockings during ablation. The dramatically shortened length of stay further compounds the risk, as patients are often discharged before postoperative chemical prophylaxis can be initiated. Unpacking the precise causes of and solutions for this rare but severe complication will be highly consequential for patient safety.

As anticipated, the prospective seizure freedom rates at 2 years were 58.4%, nearly identical to the 58.0% reported in retrospective studies ⁹ and the 56.0% seen in the unpublished SLATE trial (results reported on ClinicalTrials.gov, NCT02844465). Throughout the article, Landazuri et al frequently benchmark their 58.4% success rate against the 58% rate from the older Wiebe RCT. While this comparison is rhetorically attractive, it may not be the most scientifically representative point of reference. For instance, the more recent ERSET trial for open MTLE surgery reported a seizure freedom rate of 73% at 2 years. ² Furthermore, modern prospective (non-randomized) studies of temporal lobectomy routinely report outcomes in the 70% range or higher, aligning closer to the ERSET data than to Wiebe. ³ Surgical outcomes have naturally improved in the decades since the Wiebe RCT finished enrollment in 2000: neuronavigation is now ubiquitous, neuroimaging has advanced considerably, and preoperative seizure localization is superior; notably, only 15% (six of 40) of surgical patients in the Wiebe trial underwent intracranial monitoring, compared to 76% (110 of 145) in the LAANTERN cohort.

Despite these caveats, LAANTERN definitively confirms that laser ablation is highly effective compared to continued medical management for suitable patients with DRE. In light of modern trials reporting temporal lobectomy seizure freedom rates of 72%, ³ LITT likely trails open surgery by 10% to 15%. While a head-to-head randomized trial would be ideal, such a trial is practically infeasible. The available data imply a number-needed-to-treat of seven to 10—the number of temporal lobectomies that would need to be performed in lieu of LITT to yield one additional seizure-free patient. Importantly, just as open resections have evolved, LITT techniques will also improve, potentially narrowing this gap. Whether the reduced morbidity of LITT is worth this reduction in absolute effectiveness is a highly individualized decision to be made between patients and their physicians.

Beyond absolute seizure freedom, the LAANTERN registry provides critical longitudinal data on quality of life. Landazuri et al report improvements in QOLIE-31 scores at nearly all assessed time points, particularly in seizure worry, medication effects, and social functioning. Unsurprisingly, these improvements were most pronounced in patients who achieved an Engel 1 or ILAE 1/2 outcome, affirming that LITT's minimally invasive nature translates to tangible, patient-reported benefits.

Ultimately, having a safe, effective, minimally invasive alternative to open resection is a tremendous boon to people with epilepsy, particularly those who might otherwise decline surgery due to fear of a craniotomy. The LAANTERN registry provides reassuring prospective evidence that LITT delivers clinically meaningful seizure control alongside significant improvements in quality of life. While anterior temporal lobectomy remains the gold standard for absolute efficacy, LITT expands our armamentarium. By lowering the barrier to entry, laser ablation has the potential to narrow the surgical treatment gap, offering a tolerable and life-altering option to a broader population of patients with drug-resistant epilepsy.