Neuromodulation Shows Early Success in Epilepsy Treatment

Sandipan Pati, MD, assistant professor, department of neurology, UAB

Sandipan Pati, MD

The University of Alabama at Birmingham (UAB) recently created a neuromodulation clinic for patients with epilepsy in an attempt to fill the gaps in bringing these treatments to this patient population—as 15% to 40% still experience seizures despite these intervention advancements.¹

Now, 19 months into operation, Sandipan Pati, MD, assistant professor, department of neurology, UAB, and colleagues have reported that of the 43 patients with drug-resistant epilepsy who have been treated (vagus nerve stimulation [VNS], 27; responsive neurostimulation [RNS], 16) 44% to 69% have experienced a >60% decrease in seizures.²

"There is a significant challenge in integrating these neuromodulation therapies in clinical practice, including appropriate patient selection, education for informed decision-making, availability of trained physicians to implant the device safely, and programming or troubleshooting the device to optimize therapy,” Pati said in a statement.

Of those treated with VNS, 7 had generalized epilepsy while 20 had focal/multifocal, and the patients were an average age of 34.2 years (range, 19—60). At baseline, they were taking a mean of 3.1 (range, 2–6) antiepileptic drugs. Of those treated with RNS, their epilepsy was localized to the bi-mesial temporal lobe in 5 patients, the dominant temporal lobe in 8, and the eloquent cortex (sensory-motor, Broca's) in 3. The mean patient age was 38.8 years (range, 28–58) and at baseline, they were taking a mean 3.28 (range, 2–5) antiepileptic drugs. Within the RNS cohort, 3 patients had prior VNS that was deactivated, and 1 subject had concurrent VNS and RNS therapies.

In total, 40% (n = 17) of patients participated in the research—5 in a state-sponsored cannabidiol oil therapy study, 8 in a company-sponsored observational study, and 4 in a validating seizure warning watch study—while 28% (n = 12) were referred for additional diagnostic examination. The reasons for the diagnostic study included for potential epilepsy surgery (n = 4), diagnostic clarification prior to VNS implantation (n = 3), discrepancy in seizure count (n = 3), and confirmation of atypical spell (n = 2).

“Epilepsy neuromodulation clinic can serve as an optimal solution for patients as well as providers due to rapid access, better continuity of care, higher recruitment for research studies, and training health professionals,” Pati and colleagues wrote. “Physicians can closely monitor the patient's clinical course and recruit appropriate patients for clinical trials to advance science, and use this clinic as a resource to educate and train future specialist related to this field.”

For those in the VNS group, 25% (n = 7) had a new implant while 49% (n = 13) renewed their battery during the study period. All told, 44% (n = 12) self-reported a ≥60% reduction in seizures at follow-ups, 8+ months post-implantation, though none were seizure-free. Of that cohort, 15% (n = 4) were non-responders. The most tolerated stimulation current was between 1.5‐2.25 mA, with this identified within 8 to 13 weeks.

As for safety in the VNS cohort, 41% (n = 11) reported cough and hoarseness, which were transient. A single patient had symptomatic partial vocal cord paralysis that was attributed to chronic VNS stimulation and the device was switched off.

For the RNS group, implantations were bilateral hippocampal (n = 5), unilateral temporal (n = 8), and fronto‐parietal (n = 3), and 69% (n = 11) patients self-reported a >60% reduction in seizures, and 25% (n = 4) achieved seizure-freedom.

With regard to safety, 1 patient reported transient eye and face twitching with ipsilateral hippocampal RNS depth electrode stimulation, though symptoms resolved with current decrease. A single patient in the RNS group with a bilateral hippocampal RNS implant had probable sudden unexpected death in epilepsy (SUDEP). This individual had reported an initial decrease in seizure severity, Pati et al. noted, but later had increased bilateral tonic‐clonic seizures prior to death.

"Here, we have demonstrated the value of organizing a specialized clinic with a focus on rapid accessibility," Pati said in a statement. "Having a specialized neuromodulation clinic allows efficient management of resources, like scheduling field engineers to attend the clinic and avoiding multiple visits within a week. Also, one important aspect of titrating stimulation is patient tolerability, and the clinic provided rapid access within three weeks to manage stimulation-related [adverse] effects."

REFERENCES

1. Bringing neuromodulation therapies to drug-resistant epilepsy patients [press release]. Birmingham, AL: UAB; Published June 25, 2019. eurekalert.org/pub_releases/2019-06/uoaa-bnt062519.php. Accessed July 26, 2019.

2. Jamy R, Kaur M, Pizarro D, Toth E, Pati S. Practice trends and the outcome of neuromodulation therapies in epilepsy: A single‐center study. Epilepsia. Published June 5, 2019. doi: 10.1002/epi4.12345.