Succop Benjamin Sterling, Seas Andreas, Woo Joshua, Bode Padron Kevin Jesus, Bartlett Alyssa M, Shah Bhavya, Agashe Shruti, Harward Ii Stephen
Department of Neurosurgery, Duke University, Durham, North Carolina, USA.
School of Medicine, Duke University, Durham, North Carolina, USA.
Stereotact Funct Neurosurg. 2025;103(3):166-188. doi: 10.1159/000545716. Epub 2025 Apr 23.
Epilepsy is the fourth most common neurological disorder, affecting nearly 1% of the global population. Despite recent advancements in medical therapies, approximately one-third of patients remain refractory to treatment, necessitating consideration of surgical intervention. Historically, epilepsy surgery has been invasive and maximalist in nature, involving extensive brain resections with significant risk for morbidity. However, emerging approaches offer promising, less-invasive alternatives. One such technique is focused ultrasound (FUS), a rapidly evolving, incisionless, image-guided therapy that allows physicians to precisely target specific brain regions with ultrasonic energy to achieve a range of therapeutic effects.
Systematic methods were implemented to define the scope of preclinical and clinical applications of FUS to treat epilepsy. Inclusion criteria included preclinical experiment, case study, case series, cohort studies, and clinical trials involving therapeutic application of FUS for treatment of epilepsy of any etiology. The primary exclusion criterion was FUS for indications other than treatment of epilepsy.
Forty-six published articles and 9 ongoing clinical trials were included for a total of 55 studies. For ablative therapies, 10 studies were identified, of which 2 were preclinical studies, 1 was a clinical proof-of-concept study, 3 were clinical case reports, 1 was a completed clinical pilot study, and 3 were ongoing Phase I-Phase II clinical trials. For neuromodulatory FUS, 30 studies were identified, of which 19 were preclinical studies, 1 was a clinical case report, 4 were clinical pilot studies, and 6 were ongoing Phase I-Phase II clinical trials. Lastly, with respect to FUS-mediated blood-brain barrier (BBB) opening studies, 15 were identified, all of which were preclinical studies.
Currently, FUS has been clinically applied for targeted brain ablation (high intensity [HIFU]) and neuromodulation (low intensity [LIFU]), with recent basic science applications of sonogenetics and targeted drug delivery through the BBB (Precise Intracerebral Noninvasive Guided, or PING, Surgery) offering new opportunities for clinical translation. This review summarizes preclinical and clinical applications of FUS for epilepsy treatment, addresses challenges to implementation, and explores key areas for future research.
癫痫是第四常见的神经系统疾病，影响着全球近1%的人口。尽管近年来医学治疗取得了进展，但仍有大约三分之一的患者对治疗无效，因此需要考虑手术干预。从历史上看，癫痫手术具有侵入性且较为激进，涉及广泛的脑切除，存在较高的发病风险。然而，新出现的方法提供了有前景的、侵入性较小的替代方案。其中一种技术是聚焦超声（FUS），这是一种快速发展的、无需切口的、图像引导的治疗方法，它使医生能够利用超声能量精确靶向特定脑区，以实现一系列治疗效果。
采用系统方法来确定FUS治疗癫痫的临床前和临床应用范围。纳入标准包括临床前实验、病例研究、病例系列、队列研究以及涉及将FUS用于治疗任何病因癫痫的临床试验。主要排除标准是FUS用于治疗癫痫以外的适应症。
共纳入46篇已发表文章和9项正在进行的临床试验，总计55项研究。对于消融治疗，确定了10项研究，其中2项为临床前研究，1项为临床概念验证研究，3项为临床病例报告，1项为已完成的临床试点研究，3项为正在进行的I期-II期临床试验。对于神经调节性FUS，确定了30项研究，其中19项为临床前研究，1项为临床病例报告，4项为临床试点研究，6项为正在进行的I期-II期临床试验。最后，关于FUS介导的血脑屏障（BBB）开放研究，确定了15项，均为临床前研究。
目前，FUS已在临床上应用于靶向脑消融（高强度[HIFU]）和神经调节（低强度[LIFU]），最近的基础科学应用如声遗传学和通过血脑屏障的靶向药物递送（精确脑内无创引导，或PING，手术）为临床转化提供了新机会。本综述总结了FUS在癫痫治疗中的临床前和临床应用，探讨了实施过程中的挑战，并探索了未来研究的关键领域。
