By Viorica Hrincu, Patrick J. McDonald, and Judy Illes



This post is part of a series featuring authors who have received the Neuroethics R01 (Research Project Grants) supported by the NIH BRAIN Initiative. These research projects specifically address prominent ethical issues arising from emerging technologies and advancements in human brain research.

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Over 500,000 children in the USA and Canada suffer from epilepsy today (1,2). Thirty percent of children with epilepsy continue to have seizures while on anti-seizure medication, a condition known as drug resistant epilepsy (DRE). Unmanaged, epilepsy can result in cognitive decline, social isolation and poor quality of life, and has substantial economic impact on families and society. Novel neurotechnologies, including minimally invasive and neuromodulatory options for seizure control, represent a new frontier for improving the subjective and objective quality of life for pediatric DRE patients. Best practices do not currently exist for most neurotechnologies as interventions for pediatric DRE. This highlights a need for a better understanding of caregiver and clinician decision-making and communication for optimal treatment. By engaging affected stakeholders and using a pragmatic neuroethics framework, it will be possible to identify critical features for choice of treatment and provide practical solutions to facilitate decision-making.

Neurotechnological interventions & conventional surgery in children with DRE 

Given proper selection, conventional epilepsy surgery is an effective treatment for a portion of the pediatric DRE population. Up to 70% of properly selected children with DRE become seizure free after a surgical intervention (3). Successful surgery encourages long-term improvements in behaviour, emotion and psychosocial interactions (4) as well as health-related quality of life (5). Not all children are good candidates for conventional neurosurgical procedures such as temporal lobectomy or cortical resection.

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However, conventional epilepsy surgery is invasive and comes with significant risk. It often involves a large scalp incision, temporary removal of the skull and removal of the epileptic region of the brain. In extreme cases, removal or disconnection of the entire affected hemisphere may be necessary. Post-surgery risks include: infection, injury to adjacent areas of the brain, memory impairment, stroke, hemorrhage and death. Recovery can be lengthy with a relatively prolonged stay in the hospital and a post-hospital transition phase. Due to these caveats, parents and the medical community are seeking less invasive treatment options for pediatric DRE.

Recent technological advances over the past several decades have resulted in less invasive therapies for epilepsy in pediatric neurosurgery. These technologies include: MRI-guided laser interstitial thermal therapy (LITT), robot assisted stereo EEG (rSEEG), stereotactic radiosurgery (SRS), vagal nerve stimulation (VNS), and responsive neurostimulation (RNS). Some serve to replace more invasive surgical treatments such as neuroendoscopy. Others provide an innovative surgical treatment for conditions with limited options.

Critical barriers in the treatment of pediatric DRE 

Complexity of neurotechnology ethics landscape

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The rapid emergence of different technologies with varied attributes adds complexity to decision-making and counseling, especially for patients whose brains are still developing. Few innovative neurosurgical interventions are put through the rigors of a randomized controlled trial, as almost all novel pharmaceuticals are. Many of these therapies are tested on adult patients first, with unclear evidence as to whether the treatment results are generalizable to children. Contextual factors also influence the ethical magnitude of benefit weighed against associated risks perceived by stakeholders. These factors include: personal demands for technology, professional costs to surgeons in learning and administering new procedures, and commercial pressures imposed by aggressive promotion of technologies by manufacturers (6).

Inadequate information and communication 

Decision-making about novel neurotechnologies by health care providers and parents is often made in the context of incomplete evidence regarding the efficacy, safety and long-term side effects (7). The 2012 Priorities in Pediatric Epilepsy Workshop (October 23-24, 2012, Chicago, IL) uncovered a suite of stakeholder priorities in pediatric epilepsy research and treatment interventions. These priorities inform thinking about the medical and ethical effects of new, less invasive interventions on DRE. Unsurprisingly, seizure control was the chief concern of parents of children with epilepsy. Also of concern was the possibility of irreversible and deleterious health outcomes due to early childhood seizures and subsequent lifelong disability and dependency. A lack of adequate information and communication about how to make the best epilepsy treatment decisions for a child were seen as significant and critical barriers to these challenges (8).

A focus on decision-making 

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Using a pragmatic neuroethics framework, the ethical imperative is to identify and characterize key factors in decision-making among carers (parents, guardians) of children with epilepsy and their physicians (pediatric neurosurgeons and pediatric neurologists) when evaluating whether to utilize a novel neurotechnology. Pragmatic neuroethics emphasizes the importance of empirical analyses over a priori moral principles, proactive, solution-oriented inquiry, and the understanding of ethical behaviour in practical, real world contexts (9).

This NIH/NIMH BRAIN-funded study “Informing Choice for Neurotechnological Innovation in Pediatric Epilepsy Surgery” (1RF1 MH117805), led by Professor Judy Illes (Neurology) and Dr. Patrick McDonald (Neurosurgery) at Neuroethics Canada at UBC is designed to recruit stakeholders in Canada and the USA and invite them to share their experiences, priorities, and expertise when navigating the treatment landscape. What do physicians consider when recommending treatment? How do parents choose one treatment over another? These discussions will inform the discrete choice experiment (DCE) methodology to determine key attributes of decisions surrounding conventional and novel DRE interventions. The final step of the study is to integrate the findings from the above to create and deliver patient-directed, informational resources and clinician resources on familial decision-making.

Summary

The aim of this study is to engage affected families and clinicians to address the knowledge gap and ethical considerations related to novel, minimally invasive and neuromodulatory interventions in the treatment of pediatric DRE. The information obtained from two different health care systems (single payer and blended public/private) will be used to provide practical support and solutions to reduce the burden of related choices and challenges. Understanding and incorporating the values of families and the expertise of clinicians promotes the decision-making capacities of families and hopefully reduces the potential impact of untreated pediatric DRE.

1.  Joshi, S. M., Singh, R. K., & Shellhaas, R. A. (2013). Advanced Treatments for Childhood Epilepsy: Beyond Antiseizure Medications. JAMA Pediatrics, 167(1), 76-83. https://doi.org/10.1001/jamapediatrics.2013.424 
2. Prasad, A. N., Sang, X., Corbett, B. A., & Burneo, J. G. (2011). Prevalence of Childhood Epilepsy in Canada. Canadian Journal of Neurological Sciences, 38(5), 719-722. https://doi.org/10.1017/S0317167100054081 
3. Muh, C. R. (2016). Current and Emerging Surgical Therapies for Severe Pediatric Epilepsies. Seminars in Pediatric Neurology, 23(2), 143-150. https://doi.org/10.1016/j.spen.2016.05.005 
4. Hannan, S., Cross, J. H., Scott, R. C., Harkness, W., & Heyman, I. (2009). The effects of epilepsy surgery on emotions, behavior, and psychosocial impairment in children and adolescents with drug-resistant epilepsy: A prospective study. Epilepsy & Behavior, 15(3), 318-324. https://doi.org/10.1016/j.yebeh.2009.04.007 
5. Titus, J. B., Lee, A., Kasasbeh, A., Thio, L. L., Stephenson, J., Steger-May, K., … Smyth, M. D. (2013). Health-related quality of life before and after pediatric epilepsy surgery: The influence of seizure outcome on changes in physical functioning and social functioning. Epilepsy & Behavior, 27(3), 477-483. https://doi.org/10.1016/j.yebeh.2013.03.003 
6. Wilson, C. B. (2006). Adoption of new surgical technology. BMJ, 332(7533), 112-114. https://doi.org/10.1136/bmj.332.7533.112 
7. Eaton, M. L., & Illes, J. (2007). Commercializing cognitive neurotechnology—The ethical terrain. Nature Biotechnology, 25(4), 393-397. https://doi.org/10.1038/nbt0407-393 
8. Berg, A. T., Baca, C. B., Loddenkemper, T., Vickrey, B. G., & Dlugos, D. (2013). Priorities in pediatric epilepsy research. Neurology, 81(13), 1166. https://doi.org/10.1212/WNL.0b013e3182a55fb9 
9. Racine, E. (2010). Pragmatic Neuroethics: Improving Treatment and Understanding of the Mind-brain. MIT Press.