Exploring Surgical Advances for Drug-Resistant Epilepsy in Children After Neonatal Stroke

Siddharth Jain, MD, MBBS

Neonatal and perinatal arterial strokes (PAIS) are cerebrovascular events that occur in the neonatal period or during the perinatal period. They are caused by disrupted blood flow to the brain, often because of clots or arterial occlusion, leading to ischemia and potential brain injury. Notably, they are one of the most frequent causes of seizures in neonates and are the leading cause of hemiplegic cerebral palsy in children.

At the 2024 American Epilepsy Society (AES) Annual Meeting, held December 6-10 in Los Angeles, California, investigators presented a poster study examining factors influencing seizure freedom in patients with PAIS. Using data from the Pediatric Research Consortium Database, age at seizure onset was considered a significant factor, as patients with onset after 7 years had higher seizure freedom rates (76.5%) than those under 7 years (48.4%; P = .039). EEG localization also mattered; 85% with single-focus EEG findings had favorable outcomes compared with lower rates in multifocal (50%), generalized (66.7%) or mixed generalized/focal findings (25%; P = .013).

The study, which featured 78 patients who completed surgeries, showed that hemispherectomy (n = 36), callosotomy (n = 3), lesionectomies (n = 18), thermal ablation (n = 7) had higher seizure freedom rates (69%, 66%, 61% and 61%, respectively) than neuromodulation (n = 15; 6.7%; P = 0.001). Favorable outcomes ( >90% seizure reduction) occurred in 83% of hemispherectomy (n = 36), 77% of lesionectomy/lobectomy (n=18), and 100% of thermal ablation cases (n = 7; P < 0.001), while neuromodulation patients were less likely to have single ictal electrographic focus (18.2% vs. 65.6%, P = 0.002), congruent MEG (66.7% vs. 100%, P = 0.032), isolated encephalomalacia (28.6% vs. 68.3%, P = 0.004), and more likely to have PAIS-plus etiologies (33.3% vs. 4.7%, P = 0.001) compared with other procedures.

Cemal Karakas, MD

To better understand the context of these findings, NeurologyLive® sat down with study authors Siddharth Jain, MD, MBBS, and Cemal Karakas, MD. The duo, which work as pediatric epileptologists at Norton Children’s Neuroscience Institute, provided comment on the reasons behind the study, the importance of EEG localization in the pre-planning surgical process, and the variability in surgical procedure outcomes. Furthermore, the two also touched on areas for future research, including long-term impacts on cognition and motor development, the role of biomarkers, and the potential of minimally invasive techniques to improve care.

NeurologyLive: Talk a little bit about the conduct of the study as well as some of the main findings. What should neurologists and epileptologists take away from this study?

Siddharth Jain, MD, MBBS: So this study focuses on children with drug-resistant epilepsy secondary to perinatal arterial ischemic stroke, exploring surgical outcomes and the factors that influence success. One of the most striking findings is the potential of surgical interventions to significantly improve outcomes in these patients. For example, procedures like hemispherectomy and laser ablation showed high rates of seizure freedom and substantial seizure reduction. Hemispherectomy, in particular, was very effective in patients with extensive unilateral brain damage, achieving seizure freedom in nearly 70% of cases. Laser ablation, while newer and less invasive, also demonstrated great promise in well-localized cases.

Another important takeaway is the critical role of the pre-surgical workup, particularly EEG localization and neuroimaging. Patients with a single focus tended to do better compared to others, highlighting the need for a thorough and precise perioperative assessment for these patients.

What is the significance of EEG localization? Talk about how important this pre-step is.

Siddharth Jain, MD, MBBS: The findings on EEG localization are incredibly significant because they essentially serve as a roadmap for surgical planning. In our study, patients with single-focus EEG findings achieved much higher rates of seizure freedom compared to those with multifocal or generalized patterns. This tells us that when we can precisely identify the epileptic zone, we can target it with procedures like lesionectomy, lobectomy, or even laser ablation—avoiding the need for more invasive surgeries like hemispherectomy in a subset of these patients.

What this means for clinical practice is that neurologists and epileptologists need to emphasize detailed pre-surgical workups, including video EEG and complementary imaging techniques like MRI or PET. The synergy between EEG findings and imaging deepens our understanding of where seizures originate, enabling us to tailor surgical interventions to individual patients. The key takeaway here is that better localization directly translates into better outcomes. So investment in advanced diagnostic tools is critical.

Regarding the success of certain surgical procedures, do you feel as though that speaks more about the procedure itself or the patients? Or both?

Cemal Karakas, MD: I think it’s a combination of both. The success of surgical procedures like hemispherectomy or laser ablation reflects not only the efficacy of these interventions but also the characteristics of the patients selected for them. For example, hemispherectomy is typically performed on patients with extensive unilateral damage, which is often easier to localize and treat. Similarly, laser ablation is highly effective in cases with a well-defined epileptogenic zone, making it an excellent option for patients with focal cortical dysplasia or similar localized issues.

That said, the patient’s profile—such as the timing of their stroke, the presence of additional etiologies, and their overall brain plasticity—plays a critical role in determining outcomes. For instance, younger patients may have more neuroplasticity, allowing their brains to adapt better after surgery, but this same group might have more diffuse epileptogenic zones, complicating the surgical approach. So while the procedure is a key factor, the pre-surgical evaluation process that matches the right patient to the right intervention is equally important. This interplay is what makes these outcomes possible and underscores the importance of personalized medicine.

How can we expand on this type of research?

Cemal Karakas, MD: There’s so much room for further research in this field. First, I’d like to see more long-term studies that evaluate not just seizure outcomes but also cognitive, motor, and developmental trajectories in children after surgical interventions. Understanding how these surgeries affect quality of life and functionality over years, not just months, would be incredibly valuable.

Another area of interest is advancing our understanding of the pathophysiology of epilepsy following neonatal strokes. For instance, why do some children develop drug-resistant epilepsy while others don’t? What role do factors like cortical dysplasia type 3 or other structural brain changes play? If we can identify biomarkers or imaging patterns that predict outcomes, we could intervene earlier and more effectively.

I’m also very excited about the potential for minimally invasive techniques like laser ablation to become a mainstay in treating these patients. Research comparing its efficacy and safety to more invasive procedures would be particularly helpful. Lastly, exploring non-surgical options like neuromodulation or emerging pharmacological therapies in combination with surgery could provide a more holistic approach to treatment. And, of course, larger multi-center studies with standardized protocols are crucial to ensure that the findings we’re seeing can be broadly applied to improve care for children with neonatal strokes everywhere.

Siddharth Jain, MD, MBBS: I think we’re just scratching the surface with this complicated population. This study mainly tells us about the current scenario—what approaches we have and what kind of outcomes we’re seeing. But it’s opened up more questions than answers at this point.

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REFERENCE
1. Jain S, Perry S, Caraway A, et al. Factors Associated with Favorable Surgical Outcomes in Children with Drug-resistant Epilepsy Secondary to Neonatal/perinatal Arterial Stroke: Insights from Pediatric Epilepsy Research Consortium. Presented at: 2024 AES Annual Meeting; December 6-10; Los Angeles, CA. ABSTRACT 2.455