Expedited epilepsy surgery prior to drug resistance in children: a frontier worth crossing?

Abstract

Epilepsy surgery is an established safe and effective treatment for selected candidates with drug-resistant epilepsy. In this opinion piece, we outline the clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance. Our rationale for expedited surgery is based on the observations that, 1) a high proportion of patients with lesional epilepsies (e.g. focal cortical dysplasia, epilepsy associated tumours) will progress to drug-resistance, 2) surgical treatment of these lesions, especially in non-eloquent areas of brain, is safe, and 3) earlier surgery may be associated with better seizure outcomes. Potential benefits beyond seizure reduction or elimination include less exposure to anti-seizure medications (ASM), which may lead to improved developmental trajectories in children and optimize long-term neurocognitive outcomes and quality of life. Further, there exists emerging experimental evidence that brain network dysfunction exists at the onset of epilepsy, where continuing dysfunctional activity could exacerbate network perturbations. This in turn could lead to expanded seizure foci and contribution to the comorbidities associated with epilepsy. Taken together, we rationalize that epilepsy surgery, in carefully selected cases, may be considered prior to drug resistance. Lastly, we outline the path forward, including the challenges associated with developing the evidence base and implementing this paradigm into clinical care.

Early suppression of excitability in subcortical band heterotopia modifies epileptogenesis in rats

“…These hypotheses are in agreement with neuroimaging studies suggesting that the strength of the abnormal circuitry increases over time, as epilepsy progresses, in patients with gray matter heterotopia. 27 Therefore, the present work supports the notion that early corrective interventions, including surgical removal prior to drug-resistance, as recently proposed, 29 may reduce morbidity, and improve neurocognitive outcomes.…”

Pediatric epilepsy surgery from 2000 to 2018: Changes in referral and surgical volumes, patient characteristics, genetic testing, and postsurgical outcomes

“…One possible explanation could be referral hesitancy, driven either by the physician's reluctance to refer patients for presurgical evaluation, or by the patient or family declining the recommendation for presurgical evaluation 23‐25 . There is thus a need to increase awareness in families, as well as local health professionals, on the safety and benefits of epilepsy surgery, so this is viewed as an early intervention rather than a last resort 21,26 …”

Focal cortical dysplasia: a practical guide for neurologists

“…Laser interstitial thermal therapy, a minimally invasive ablation procedure of epileptogenic foci, is increasingly used in drug-resistant structural epilepsy due to the advantages of a decreased length of procedure time, shorter hospital stay and lower rates of complications when compared with open surgery 61. There is also increasing clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance in children, especially in non-eloquent brain areas, leading to better seizure, developmental and cognitive outcomes 62 63…”

“…(61) There is also increasing clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance in children, especially in non-eloquent brain areas, leading to better seizure, developmental, and cognitive outcomes. (62,63) • What to expect? Prognostic aspects Up to 70% of patients with FCD and drug-resistant epilepsy, including children with severe epileptic encephalopathies, achieve a favourable seizure outcome after surgery.…”