Epilepsy surgery is no longer considered a last resort for patients with drug-resistant seizures; however, there remain significant and systemic barriers to prompt referral to epilepsy surgery evaluation. This deprives the patient of potential treatments that may be their only hope for seizure freedom or reduction in seizure burden.
One massive barrier is the lack of surgical outcomes knowledge - especially functional outcomes in the pediatric population. This is due, in part, to a paucity of research that addresses outcomes beyond seizure control. The clinician who cannot answer the question What will happen after surgery? is less likely to make a referral for a surgical evaluation and cannot counsel a patient or parent in a meaningful way.
Epilepsy surgeries (excluding neuromodulation) are irreversible treatments. Because of this fundamental reason, they differ from medical management. Epilepsy surgeries disrupt neural circuits, sometimes causing new functional disabilities if resection of eloquent cortex is necessary. In infants and children, they change the trajectory of developing neural networks in ways we do not fully understand. (See PCORI's Interactive Meeting Summary: Functional Outcomes After Large Pediatric Epilepsy Surgeries.)
Functional compensatory neuroplasticity is our hope for a positive developmental trajectory post-operatively in children, but it can also be maladaptive. And there is a deep lack of research investigating functional, behavioral, and educational interventions to help children reach their full potential post-operatively after extensive cortical resections.
This lack of research is because epilepsy surgery is disproportionately underfunded as compared to the development of new therapeutics. Earlier this year, E. Solli and colleagues in their paper Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): A literature review pulled data from the National Institutes of Health's RePORT database of categorical funding, which showed that "of all grants in 2017 awarded for epilepsy research, 5 projects investigating surgical treatment received $1,930,150, whereas a disproportionate 10 AED-related studies were assigned $8,831,321." Given that all basic and clinical epilepsy research is grossly underfunded overall, this leaves epilepsy surgery receiving less than a quarter on the dollar of NIH epilepsy treatment funding in comparison.
This statistic piqued my interest when considering this comment, and while not necessarily comparing apples to oranges in terms of Solli's investigation above, I reviewed the 2019 RePORT database to understand recent spending on any type of epilepsy surgery research. There, I found a total of thirteen studies that mentioned "surgery" ($7,827,408), including neuromodulation, out of 503 funded studies ($187,662,561).
That is 4.2% of total epilepsy research funding awarded for any type of epilepsy surgery research last year.
When neurostimulation studies are removed from the mix, only seven studies ($6,795,002) mention epilepsy surgery.
Now, when we break it down even further, none of the "epilepsy surgery" studies investigate surgery (any type) v. medical management, or long-term cost benefits of surgery v. medical management, or efficacy of any surgical technique (e.g. laser ablation v. resection; peri-insular hemispherotomy v. endoscopic hemispherotomy). Even worse, when we consider patient-centered research, only four studies are identified: one investigates a way to predict seizure control with $176,240 awarded (answering the question "Will my child be seizure free after surgery?"); another with $406,485 awarded investigates functional outcomes vis-a-vis visual processing after posterior cortical resections (attempting to answer the very important question for parents "What will my child see after surgery?"); and a third study at $197,204 investigates MEG connectivity of functional language sites pre-operatively (attempting to answer the question "Will my child's speech be affected by surgery?") for a grand total of $779,929.
We cannot expect to make substantial progress for the 30-40% of drug-resistant patients for whom epilepsy surgery may be a successful treatment when less than 5% of the annual funding for epilepsy research is on any research which mentions epilepsy surgery, less than 4% is spent on any research which mentions resection (mostly pre-operative candidacy research), and almost 0% of spending is on patient-centered research.
To remedy this deep inequity, we propose a specific benchmark for epilepsy surgery as follows:
Identify, develop, and improve surgical interventions to terminate seizures while minimizing adverse effects, and understanding and limiting their impact on non-seizure outcomes including neurodevelopment, mental health, cognition, health-related quality of life, and other functions.
We further implore the NINDS to turn its attention to patient-centered research investigating the medical and functional impacts of various epilepsy surgeries, especially large resections in childhood. This would include:
Prevention research addressing adverse medical outcomes of large resections, notably post-operative hydrocephalus and endocrinopathies;
Treatment research addressing long-term medical follow-up, physical rehabilitation interventions, and intensive therapies to promote literacy and numeracy acquisition post-operatively.
Barriers to prompt surgical evaluation, and ultimately to surgery, are numerous. One powerful barrier is the clinician who cannot answer the question What will happen after surgery? It is time to turn our attention to funding research that answers this question. This will not happen if surgery is buried in the other benchmarks.