Effectiveness of Laser Tissue Ablation in Medically Intractable Epilepsy

By: Kyra Perham

Photo Credit: www.depositphotos.com

Introduction

Patients diagnosed with medically intractable epilepsy are predisposed to higher mortality rates than patients with controlled epilepsy. Approximately one-third of individuals diagnosed with epilepsy are considered to have medically intractable epilepsy, and more than ten percent of these patients die within the first two years of initial diagnosis. Surgical intervention is often the only viable treatment option for intractable cases. The introduction of stereotactic laser tissue ablation for medically intractable epilepsy is currently in development, and the procedure has been in practice since the early 2000s.

History of Laser Ablation

The first developments of stereotactic ablative techniques date back to the 1960s, with significant progress made through the 1990s. Radiofrequency ablation was subsequently developed and integrated into surgical practice (LaRiviere, 2016). Today, the use of Laser Interstitial Thermotherapy (LITT) is an increasingly common procedure for patients with medically intractable epilepsy as this technology is able to eliminate problem areas in the brain for epileptic patients with minimal inconsequential damage to surrounding brain tissue.

Laser ablation technology uses short-wavelength radiation against somatic tissue. Essentially, a laser beam is directed towards a mass of tissue and irradiated, and that tissue is converted into a high-temperature plasma that dissipates. During LITT procedures in epileptic patients, a laser beam ablates the portion of epileptogenic foci that acts as the starting point for epileptic activity in the brain (Shukla et. al., 2017). Once this area of the brain has been removed via thermal energy, the epileptogenic foci that originally initiated seizure activity is gone, and seizure activity will no longer originate.

 How effective is laser tissue ablation in treating medically intractable epilepsy, and what are the associated risks and benefits of the procedure?

Epilepsy is the result of recurrent abnormal electrical activity in the brain. During a seizure, there exists an unbalance between excitation and inhibition in a specific region of neurons in the brain. The mechanisms that facilitate neuron firing are disrupted, and electrical activity in the brain becomes disorganized (Scharfman, 2007). Neurons are in a state of uncontrolled firing and result in symptomatic manifestations expressed as a seizure. Seizures can be triggered by various factors, including genetic mutations, trauma to the brain, disease, medications, and more (Shorvon et. al., 2016).  However, epileptic individuals experience recurrent seizures that are often not due to external factors and are unprovoked. Instead, the brain has a low seizure threshold, which indicates that the brain has an increased level of neuron excitability.

Most cases of epilepsy can be treated through pharmaceutical medications called antiepileptic drugs that work by reducing the excitability of neurons in the brain. When seizures continue despite the introduction of antiepileptic drugs, epilepsy is considered medically intractable. There are multiple causes of such unresponsiveness, including permanent changes in neuronal functioning and connectivity, decreased synaptic plasticity, and abnormal neural circuits (Scharfman, 2007). The misfiring of neurons and incongruent excitation and inhibition cannot be altered with pharmaceutical medications, and the only treatment option is through the removal of the brain tissue.

The ictal onset zone describes the region of the brain in which the electrical misfiring originates. Surgical resection of this area has been distinguished as an effective treatment for medically intractable epilepsy. This can be done through an open craniotomy surgery, known as a lobectomy. During this, an incision is made in the scalp and part of the skull is removed, exposing large amounts of brain tissue. The ictal onset zone is removed using surgical instruments, and attempts are made to minimize damage to surrounding brain tissue. An open craniotomy is a major procedure that carries significant risk. The most common complications include intracranial bleeding, cognitive dysfunction, and neurological damage (Wood, 2021). Although an effective treatment method for intractable epilepsy, open craniotomy surgery is much more invasive than surgeries that operate using laser tissue ablation methods.

LITT is a newer treatment option that offers a less invasive procedure in removing the tissual seizure foci. During the procedure, laser energy is converted into thermal energy and targeted towards the specific region of the brain being ablated. This thermal energy causes a series of enzyme induction, protein denaturation, and membrane dissolution. This triggers the death of cells in the brain called coagulative necrosis, and the tissue is ablated (Shukla et. al., 2021). Essentially, brain tissue is dissipated by a high-energy beam of light and thermal heat.

The ablation process begins with the deep penetration of light energy into the target surface tissue. Throughout this process is a transfer of energy which involves the absorption and scattering of light by the tissue being ablated. The neuron and glial cells that make up brain tissue contain chromophores, which absorb the wavelengths of the laser light. Thus, the energy of the laser light is absorbed into the tissue (de Medeiros et. al., 2020). Once the tissue absorbs the high-energy laser light, the temperature of the tissue rises rapidly. This rise in temperature initiates the series of enzyme induction, protein denaturation, and membrane dissolution that leads to the death of the brain cells (Venugopalan, 2003). Finally, the tissue reaches a high enough temperature to vaporize, and the tissue is ablated. Compared to open surgery, studies show that LITT may be a superior resection method used to better treat medically intractable epilepsy. A study performed by Joon Y. Kang evaluates the effectiveness of LITT surgical procedures and compares the data to traditional open surgical procedures. Kang observed 20 patients who underwent LITT surgery for two consecutive years following surgery (Kang et. al., 2015). It was found that patients who underwent LITT surgery experienced minimal postoperative pain, and shorter recovery periods both in the hospital and after discharge. However, rates of seizures after surgery were higher in patients who underwent LITT surgery than those who underwent traditional open surgery (Kang et. al., 2015).

Data collection was performed through an assessment of office visits and medical documentation. Key findings showed that verbal learning and memory performance were only minimally affected, contextual memory was adequately preserved, and LITT surgery in this population showed a fifty-three percent remission rate (Kang et. al., 2015). Risks observed by this study included lower odds of seizure freedom compared to open surgery, a decline in contextual memory tasks, seizure relapse, headache, insomnia, mood symptoms, and scalp numbness. One patient experienced an adverse side effect of brain edema with hemorrhage in close proximity to the ablation site (Kang et. al., 2015).  Limitations of this study include poor longitudinal data and limited population size.

This study supports the idea of LITT acting as a safe treatment option for patients with medically intractable epilepsy. Although long-term data is not yet available to accurately determine the longitudinal effectiveness of LITT, this treatment option may be favorable in terms of post-surgical morbidity and rehabilitation ease. Reduced postoperative complications and improved recovery were found to be the key benefits of LITT within this study. In another study conducted by Scheherazade Le, a systematic review was performed that compares the efficacy of LITT procedures by tracking seizure outcomes of reported cases of surgical treatment of medically intractable epilepsy at Stanford from 2014-2017 (Scheherazade, 2018). Postoperative seizure frequency and post-ablation complications were monitored through a total of 30 patients.

Out of 30 patients, 77% who underwent LITT surgery experienced deep tissue scarring, 76% of patients had less than a 90% reduction in seizure frequency, and 31% of patients experienced complete seizure freedom. 10% of patients experienced neurological deficits, and 34% of patients experienced perioperative seizures (Scheherazade, 2018).  There were no significant complications either preoperatively or postoperatively, except for one visual field complication. Overall, the study describes the LITT procedure to stand well tolerated and the majority of patients experienced significant seizure frequency reduction (Scheherazade, 2018).

Based upon the literature analyzed, LITT surgery has shown promising results with a vast potential for future research. LITT is an effective surgical approach in the treatment of medically intractable epilepsy as evidenced by significantly reduced postoperative complications and improved recovery times, along with reduced postoperative seizure frequency. Although compared to open craniotomy surgery, LITT resulted in higher chances of postoperative seizure relapse but had significantly reduced rates of postoperative pain, hospital stay length, and recovery length. The most common risks and compilations of the procedure include minor neurological deficits, visual field abnormalities, and deep tissue scarring.

Conclusion

Laser tissue ablation is a significantly less invasive surgical approach to treating patients with medically intractable epilepsy. Approximately one-third of epilepsy patients are considered to have medically intractable epilepsy, and ten percent of patients will experience mortality within two years of their diagnosis, yielding a much higher mortality rate than seen in patients with controlled epilepsy. As such, surgical intervention is often the only viable treatment option. LITT is a minimally invasive procedure that may deter mortality in patients with medically intractable epilepsy, and research has shown the procedure to be associated with less perioperative and postoperative complications, shorter recovery periods, and minimal postoperative pain. While LITT is a relatively new procedure, longitudinal data is not available for long-term analysis. Thus, it is important to weigh the risks and benefits of LITT surgery on a case-by-case basis.

Resources:

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Kang, J. Y., Wu, C., Tracy, J., & Lorenzo, M. (2015, December 24). Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy. Wiley Online Library 57(2) 325-334

Scharfman, H. E. (n.d.). (2007, July 24) The Neurobiology of Epilepsy – PMC. NCBI Library

Scheherazade, L. (n.d.). ( 2018, October 26) Laser interstitial thermal therapy (LITT): Seizure outcomes for refractory mesial temporal lobe epilepsy. Pubmed National Library of Medicine 6;10(1), 1942

Shorvon, S. D., Perucca, E., & Engel, J. (2016). The treatment of epilepsy. John Wiley & Sons Inc.

Shukla, N. D., Ho, A. L., Pendharkar, A. V., Sussman, E. S., & Halpern, C. H. (2017, September 26). Laser interstitial thermal therapy for the treatment of epilepsy: Evidence to date. Neuropsychiatric disease and treatment. National Library of Medicine 13(1), 2469-2475

Venugopalan, V. A. (2003, February). Mechanisms of pulsed laser ablation of biological tissues. National Library of Medicine 103(2), 577-644

Wood, M. (2021, January 25). “Laser surgery becoming go-to option for epilepsy.” UChicago Medicine.

https://www.uchicagomedicine.org/forefront/neurosciences-articles/image-guided-laser-surgery becoming-go-to-option-for-epilepsy