Advertisement

Combined Neuromodulation (Vagus Nerve Stimulation and Deep Brain Stimulation) in Patients With Refractory Generalized Epilepsy: An Observational Study

Published:September 12, 2022DOI:https://doi.org/10.1016/j.neurom.2022.08.449

      Abstract

      Introduction

      This article describes our findings while treating patients with refractory generalized epilepsy with combined vagus nerve stimulation (VNS) and centro-median deep brain stimulation (CMDBS).

      Materials and Methods

      A total of 11 consecutive patients with refractory generalized epilepsy (ten with Lennox-Gastaut syndrome) previously submitted to VNS and who subsequently underwent CMDBS were retrospectively studied. The VNS final parameters were 2 to 2.5 mA, 30 Hz, and 500 μs, cycling mode, 30 seconds “on” and 5 minutes “off” for all patients. The CMDBS final parameters were 4 to 5 V, 130 Hz, and 300 μs, bipolar, continuous stimulation in all patients.

      Results

      There were eight male participants, ranging in age from eight to 49 years (mean 19 years). Follow-up time after VNS ranged from 18 to 132 months (mean 52 months) and from an additional 18 to 164 months (mean 42 months) during combined VNS-CMDBS. All patients had daily seizures. Atypical absences were noted in eight patients, tonic seizures in seven, bilateral tonic-clonic seizures in four, atonic seizures in three, and myoclonic seizures in two patients. Four patients were initially considered responders to VNS. All these patients also had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Seven patients were not responders to VNS, and of those, four had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Eight patients had an additional >50% reduction in seizure frequency when moved from VNS alone to VNS-CMDBS therapy. There were two nonresponders during combined VNS-CMDBS therapy, and both were nonresponders to VNS alone. Nine patients were considered responders during VNS-CMDBS combined therapy compared with baseline.

      Discussion

      This study showed that combined VNS-CMDBS therapy was able to double the number of responders compared with VNS alone in a cohort of patients with refractory generalized epilepsy. We believe these data represent the first evidence that combined neuromodulation may be useful in this quite homogeneous patient population.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Toffa D.H.
        • Touma L.
        • El Meskine T.
        • Bouthillier A.
        • Nguyen D.K.
        Learnings from 30 years of reported efficacy and safety of vagus nerve stimulation (VNS) for epilepsy treatment: a critical review.
        Seizure. 2020; 83: 104-123
        • Cukiert A.
        • Cukiert C.M.
        • Burattini J.A.
        • et al.
        A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy.
        Neuromodulation. 2013; 16 ([discussion: 556]): 551-556
        • Geller E.B.
        • Skarpaas T.L.
        • Gross R.E.
        • et al.
        Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.
        Epilepsia. 2017; 58: 994-1004
        • Salanova V.
        • Witt T.
        • Worth R.
        • et al.
        Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy.
        Neurology. 2015; 84: 1017-1025
        • Velasco F.
        • Velasco M.
        • Velasco A.L.
        • Jimenez F.
        • Marquez I.
        • Rise M.
        Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies.
        Epilepsia. 1995; 36: 63-71
        • Cukiert A.
        • Cukiert C.M.
        • Burattini J.A.
        • Mariani P.P.
        Seizure outcome during bilateral, continuous, thalamic centromedian nuclei deep brain stimulation in patients with generalized epilepsy: a prospective, open-label study.
        Seizure. 2020; 81: 304-309
        • Vonck K.
        • Boon P.
        • Claeys P.
        • Dedeurwaerdere S.
        • Achten R.
        • Van Roost D.
        Long-term deep brain stimulation for refractory temporal lobe epilepsy.
        Epilepsia. 2005; 46: 98-99
        • Cukiert A.
        • Cukiert C.M.
        • Burattini J.A.
        • Mariani P.P.
        Long-term seizure outcome during continuous bipolar hippocampal deep brain stimulation in patients with temporal lobe epilepsy with or without mesial temporal sclerosis: an observational, open-label study.
        Epilepsia. 2021; 62: 190-197
        • Velasco A.L.
        • Velasco F.
        • Velasco M.
        • Jiménez F.
        • Carrillo-Ruiz J.D.
        • Castro G.
        The role of neuromodulation of the hippocampus in the treatment of intractable complex partial seizures of the temporal lobe.
        Acta Neurochir Suppl. 2007; 97: 329-332
        • Fisher R.
        • Salanova V.
        • Witt T.
        • et al.
        Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.
        Epilepsia. 2010; 51: 899-908
        • Morrell M.J.
        • RNS System in Epilepsy Study Group
        Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.
        Neurology. 2011; 77: 1295-1304
        • Cukiert A.
        • Cukiert C.M.
        • Burattini J.A.
        • Mariani P.P.
        • Bezerra D.F.
        Seizure outcome after hippocampal deep brain stimulation in patients with refractory temporal lobe epilepsy: a prospective, controlled, randomized, double-blind study.
        Epilepsia. 2017; 58: 1728-1733
        • Cukiert A.
        • Lehtimäki K.
        Deep brain stimulation targeting in refractory epilepsy.
        Epilepsia. 2017; 58: 80-84
        • Parisi V.
        • Lundstrom B.N.
        • Kerezoudis P.
        • Alcala Zermeno J.L.
        • Worrell G.A.
        • Van Gompel J.J.
        Anterior nucleus of the thalamus deep brain stimulation with concomitant vagus nerve stimulation for drug-resistant epilepsy.
        Neurosurgery. 2021; 89: 686-694
        • Park H.R.
        • Choi S.J.
        • Joo E.Y.
        • et al.
        The role of anterior thalamic deep brain stimulation as an alternative therapy in patients with previously failed vagus nerve stimulation for refractory epilepsy.
        Stereotact Funct Neurosurg. 2019; 97: 176-182
        • Zhu J.
        • Wang X.
        • Xu C.
        • et al.
        Comparison of efficiency between VNS and ANT-DBS therapy in drug-resistant epilepsy: a one year follow up study.
        J Clin Neurosci. 2021; 90: 112-117
        • Kulju T.
        • Haapasalo J.
        • Lehtimäki K.
        • Rainesalo S.
        • Peltola J.
        Similarities between the responses to ANT-DBS and prior VNS in refractory epilepsy.
        Brain Behav. 2018; 8e00983
        • Martin R.A.
        • Cukiert A.
        • Blumenfeld H.
        Short-term changes in cortical physiological arousal measured by electroencephalography during thalamic centromedian deep brain stimulation.
        Epilepsia. 2021; 62: 2604-2614

      Comments