Multi-thalamic Neuromodulation Improves Seizure Outcome in SCN1A-Dravet Syndrome: Insights from Ambulatory Electrothalamogram
Chetan Nayak1, Vladmir Vashin1, Yash Vakilna1, Samden Lhatoo1, Sandipan Pati1
1Neurology, University of Texas Health Science Center at Houston
Objective:

We present a case of Dravet Syndrome (DS) with drug-resistant multifocal epilepsy who we successfully treated using FDA-approved sensing-enabled Percept DBS. Our therapeutic approach involved precise targeting of multiple thalami (centromedian and pulvinar) for DBS to engage and modulate putative epileptogenic circuits.

Background:
DS is a rare genetic epileptic encephalopathy caused by loss-of function SCN1A gene mutation encoding for voltage-gated sodium channel Nav 1.1. These patients are usually poor candidates for resective epilepsy surgery due to the complexity of their epileptogenic networks involving widespread cortical and subcortical nodes. Thalamic DBS neuromodulation can be a useful treatment alternative for these patients.
Design/Methods:
Our approach to selecting the thalamic neuromodulatory target in DS was driven by mapping the patient's epileptogenic circuit, which could be effectively engaged by thalamic stimulation to reduce excitability. We utilized thalamic recordings as ambulatory electronic seizure diaries to understand seizure cycles. Additionally, we tried to the explore potential mechanisms by which high-frequency continuous stimulation may intricately modulate thalamic nodal excitability.
Results:

Patient underwent DBS placement targeting the left centro-median and left pulvinar nuclei and stimulation parameters were gradually advanced during monthly follow-up. Patient experienced gradual reduction in seizure frequency and improvement in quality of life. Analysis of thalamic recordings derived from the device showed that both CM and Pulvinar presented significant circadian as well as multi-day cyclicity. We were also able to show that high-frequency stimulation of CM and Pulvinar modulates thalamic neural activity.

Conclusions:

This pioneering case study unveils a groundbreaking exploration of DS by delving into the intricacies of SCN1A channelopathy. It marks the first-ever documentation of seizure cycles, seizure clusters, and thalamic recordings in this context and underscores the immense potential of thalamic neuromodulation in alleviating the formidable seizure burden associated with DS. This case signifies progress in circuit-based therapeutics and automated seizure burden monitoring for severe channelopathies.

10.1212/WNL.0000000000204799