Clinically indicated electrical stimulation strategies to treat patients with medically refractory epilepsy

Abstract

SummaryFocal epilepsies represent approximately half of all diagnoses, and more than one‐third of these patients are refractory to pharmacologic treatment. Although resection can result in seizure freedom, many patients do not meet surgical criteria, as seizures may be multifocal in origin or have a focus in an eloquent region of the brain. For these individuals, several U.S. Food and Drug Administration (FDA)–approved electrical stimulation paradigms serve as alternative options, including vagus nerve stimulation, responsive neurostimulation, and stimulation of the anterior nucleus of the thalamus. All of these are safe, flexible, and lead to progressive seizure control over time when used as an adjunctive therapy to antiepileptic drugs. Focal epilepsies frequently involve significant comorbidities such as cognitive decline. Similar to antiepilepsy medications and surgical resection, current stimulation targets and parameters have yet to address cognitive impairments directly, with patients reporting persistent comorbidities associated with focal epilepsy despite a significant reduction in the number of their seizures. Although low‐frequency theta oscillations of the septohippocampal network are critical for modulating cellular activity and, in turn, cognitive processing, the coordination of neural excitability is also imperative for preventing seizures. In this review, we summarize current FDA‐approved electrical stimulation paradigms and propose that theta oscillations of the medial septal nucleus represent a novel neuromodulation target for concurrent seizure reduction and cognitive improvement in epilepsy. Ultimately, further advancements in clinical neurostimulation strategies will allow for the efficient treatment of both seizures and comorbidities, thereby improving overall quality of life for patients with epilepsy.

Closed-loop stimulation of the medial septum terminates epileptic seizures

“…Medial septum E-stim has been suggested for clinical studies after the finding that theta rhythm medial septum stimulation reduces seizure susceptibility (Fisher, 2015;Izadi et al, 2018). Together with the previous findings on open-loop stimulation of the medial septum (Miller et al, 1994;Izadi et al, 2019), our results indicate that a single electrode in the medial septum can be used for dual purposes: seizure termination via closedloop seizure rhythm-driven stimulation during ictal periods, and seizure prevention via open-loop theta rhythm stimulation during pre-ictal seizure-initiation periods.…”

Seizure detection devices for use in antiseizure medication clinical trials: A systematic review

“…SDDs can also improve endpoint reporting in anti-seizure device (ASD) clinical trials. The most common ASDs employ targeted brain stimulation to reduce the occurrence and severity of seizures, often in refractory epilepsy patient populations [80,81]. Prominent ASDs include a responsive neurostimulation system (RNS), vagus nerve stimulation (VNS) devices, and deep brain stimulation (DBS) devices [80].…”

“…The most common ASDs employ targeted brain stimulation to reduce the occurrence and severity of seizures, often in refractory epilepsy patient populations [80,81]. Prominent ASDs include a responsive neurostimulation system (RNS), vagus nerve stimulation (VNS) devices, and deep brain stimulation (DBS) devices [80]. Similarly to ASM efficacy, ASD effectiveness is currently evaluated by utilizing PROMs to assess changes in seizure frequency [76].…”

Bifurcation Analysis of a Two-Dimensional Neuron Model under Electrical Stimulation

“…For example, external stimulating currents or external electric fields can affect the excitability of nervous system and the generation and conduction of nervous system information [25][26][27]. On the other hand, electrical stimulation has become an emerging means of treating neuropsychiatric diseases [28,29]. More and more bodies of evidence show that regulation and improvement of brain function can be achieved by changing the amplitude, frequency, and other parameters of stimulation [30,31].…”