Neuromodulation beyond neurostimulation for epilepsy: scope for focused ultrasound

ABSTRACT

Introduction: Epilepsy is one of the most common neurological disorders and is often difficult to control with medication. Intractable epilepsy often results in compromised quality of life (QOL), neurologic morbidity and even mortality. In carefully selected cases, resective surgery offers the best potential for cure or seizure control. However, a large proportion of patients are not suitable for resective epilepsy surgery. Neuromodulation techniques are increasingly being used to treat such refractory cases. Recently, the FDA approved Magnetic Resonance-guided Focused Ultrasound (MRgFUS) for essential tremor and this novel technology is also being explored in several other neuropsychiatric conditions and neurological disorders, including epilepsy.

Area covered: While the literature is scant and scattered, the pertinent literature of the MRgFUS is reviewed with an emphasis on research relevant to its application for epilepsy.

Expert opinion: Limited preliminary clinical experiences and research studies with MRgFUS ablation or neuromodulation for epilepsy have shown promising results; however, this procedure remains experimental requiring further investigations. Safe and reversible opening of the blood-brain barrier (BBB) with MRgFUS adds an additional therapeutic avenue by allowing targeted delivery of neurotherapeutics in neurological disorders, potentially including epilepsy. Ongoing clinical trials and research coupled with technological advancements contribute to strengthening the MRgFUS epilepsy field. MRgFUS could be the future technology of choice for ‘ablation’ or ‘sononeuromodulation’, and/or a ‘targeted therapeutics’ for epilepsy.

KEYWORDS:

• Intractable epilepsy
• epilepsy surgery
• neuromodulation
• focused ultrasound
• MRgFUS

Article highlights

• Epilepsy surgery, neuromodulation, and ablation are effective in seizure control/freedom in properly selected cases of intractable epilepsy.

• MRgFUS has emerged as the non-invasive transcranial procedure for brain lesioning/ablation and has been approved for tremor in ET/PD.

• Non-ablative MRgFUS neuromodulation and targeted therapies are being explored in many neurological disorders as well as its potential to reversibly and spatially precisely open the blood-brain barrier (BBB).

• Epilepsy is at the forefront of the neurological disorders being explored for MRgFUS, as epileptic zones and networks are well delineated and potentially amenable for focal ablation, disconnections, or pathway modulations.

• Various clinical trials and ongoing research studies will further validate and potentiate the role of MRgFUS in epilepsy.

• MRgFUS holds promise to become a preferred surgical intervention for epilepsy, by using its non-invasive neuroablative and neuromodulation functions.

Acknowledgments

The authors wish to dedicate this paper in the fond memory and pioneering work of MRgFUS in epilepsy by Dr. Sanjiv Bhatia, MD, Division of Pediatric Neurological Surgery, Nicklaus Children’s Hospital Brain Institute, University of Miami, FL, USA. His sudden demise during the manuscript preparation was a painful loss not only to the co-authors but to the neuroscience and the medicine community as such. We are grateful to his ideas about this paper, his expertise and his continued effort to explore better and minimally invasive treatment options for epilepsy.

Authors wish to thank Mr. Mor Dayan and Mr. David Tilden, Insightec Inc. for their valuable support for the figures used in the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.