Neuromodulation Techniques in Children with Super-Refractory Status Epilepticus

Abstract

Status epilepticus (SE) is a life-threatening condition and medical emergency which can have lifelong consequences, including neuronal death and alteration of neuronal networks, resulting in long-term neurologic and cognitive deficits in children. When standard pharmacological treatment for SE is not successful in controlling seizures, the condition evolves to refractory SE (rSE) and finally to super-refractory SE (srSE) if it exceeds 24 h despite using anaesthetics. In this systematic review, we present literature data on the potential uses of clinical neuromodulation techniques for the management of srSE in children, including electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation. The evaluation of these techniques is limited by the small number of published paediatric cases (n = 25, one with two techniques) in peer-reviewed articles (n = 18). Although neuromodulation strategies have not been tested through randomised, prospective controlled clinical trials, this review presents the existing data and the potential benefits of neuromodulation therapy, suggesting that these techniques, when available, could be considered at earlier stages within the course of srSE intending to prevent long-term neurologic complications. Clinical trials aiming to establish whether early intervention can prevent long-term sequelae are necessary in order to establish the potential clinical value of neuromodulation techniques for the treatment of srSE in children.

Keywords: children epilepsy; deep brain stimulation; electroconvulsive therapy; neuromodulation; super-refractory status epilepticus; vagus nerve stimulation.

Figure 1

Invasive and non-invasive neuromodulation techniques tried in children with srSE. (A) Electrodes and typical positions for non-invasive electroconvulsive therapy (ECT); (B) X-ray showing vagus nerve stimulation (VNS) in a 14 y/o child. The white arrow indicates the position of the stimulating contacts in the vagus nerve; (C) X-ray showing deep brain stimulation (DBS) in a 12 y/o child. The white arrow indicates the DBS position in the centromedian thalamic nucleus in the brain.

Figure 2

PRISMA 2020 flow diagram for new systematic reviews. * 6 studies reported epilepsia partialis continua, 1 study reported asleep electrographic status epilepticus, 1 study reported Rasmussen’s encephalitis, and 3 studies where neuromodulation did not directly treat the status epilepticus.

Figure 3

Timeline of srSE patients treated with ECT. (? = the time period is estimated but not clearly stated) [53,59,60,61,62].

Figure 4

Timeline of srSE patients treated with VNS (* about 30 days but not clearly stated; ? = the time period is estimated but not clearly stated) [52,54,55,56,57,58,63,64,65].

Figure 5

Timeline of srSE patients treated with DBS [52,66,67,68,69].