Impact of Cardiac‐Based Vagus Nerve Stimulation Closed‐Loop Stimulation on the Seizure Outcome of Patients With Generalized Epilepsy: A Prospective, Individual‐Control Study

Object Vagus nerve stimulation (VNS) is approved by the FDA for the treatment of partial epilepsy in patients older than 12 years. Authors of the current study performed a large retrospective analysis and comparison of VNS outcomes in children with an age ≥ and < 12 years, including those with partial and generalized epilepsy. Methods A retrospective review of the records of pediatric patients (age < 18 years) who had undergone primary VNS system implantation between 2001 and 2010 by a single pediatric neurosurgeon was undertaken. Considered data included demographics, epilepsy type (partial vs generalized), seizure frequency, seizure duration, postictal period duration, and antiepileptic medication use. Results One hundred forty-six patients (49% female) were followed up for a mean of 41 months after VNS implantation. Thirty-two percent of patients had partial epilepsy and 68% had generalized epilepsy. After VNS system implantation, seizure frequency was reduced in 91% of patients, seizure duration in 50%, postictal period in 49%, and antiepileptic medication use in 75%. There was no significant difference in age, sex, or duration of follow-up according to epilepsy type. Neither was there any significant difference in seizure frequency reduction, seizure duration, postictal period, medication use, overall clinical improvement, or improvement in quality of life based on an age ≥ or < 12 years or epilepsy type. Conclusions Vagus nerve stimulation reduced both seizure frequency and antiepileptic medication use in the majority of pediatric patients regardless of sex, age cohort, or epilepsy type. Vagus nerve stimulation also reduced seizure duration and postictal period in approximately half of the pediatric patients. Contrary to expectation, children with partial epilepsy do not benefit from VNS at higher rates than those with generalized epilepsy.

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Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy

Epilepsy & Behavior ◽

10.1016/j.yebeh.2020.107253 ◽

2020 ◽

Vol 111 ◽

pp. 107253

Author(s):

Ana Suller Marti ◽

Seyed Mohammad Mirsattari ◽

Keith MacDougall ◽

David Andrew Steven ◽

Andrew Parrent ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Generalized Epilepsy

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Neuromodulation Therapy with Vagus Nerve Stimulation for Intractable Epilepsy: A 2-Year Efficacy Analysis Study in Patients under 12 Years of Age

Epilepsy Research and Treatment ◽

10.1155/2016/9709056 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 8

Author(s):

Suresh Gurbani ◽

Sirichai Chayasirisobhon ◽

Leslie Cahan ◽

SooHo Choi ◽

Bruce Enos ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Focal Epilepsy ◽

Intractable Epilepsy ◽

Cumulative Effect ◽

Adjunctive Treatment ◽

Seizure Freedom ◽

Primary Generalized Epilepsy ◽

Generalized Epilepsy

To study the efficacy of vagus nerve stimulation (VNS) therapy as an adjunctive treatment for intractable epilepsy in patients under 12 years of age, we analyzed 2-year postimplant data of 35 consecutive patients. Of the 35 patients, 18 (51.4%) at 6 months, 18 (51.4%) at 12 months, and 21 (60.1%) at 24 months showed ≥50% reduction in seizure frequency (responders). Although incremental seizure freedom was noted, no patient remained seizure-free throughout the 3 study periods. Partial response (≥50% seizure reduction in 2 or less study periods) was seen in 8 (22.9%) patients. Twelve patients (34.3%) were nonresponders. Out of 29 patients with primary generalized epilepsy, 20 (68.9%) and, out of 6 patients with focal epilepsy, 3 (50%) had ≥50% seizure control in at least one study period. No major complications or side effects requiring discontinuation of VNS therapy were encountered. We conclude that (1) patients with intractable primary generalized epilepsy respond better to VNS therapy, (2) cumulative effect of neuromodulation with improving responder rate to seizure freedom with continuation of VNS therapy is noted, and (3) VNS therapy is safe and is well tolerated in children receiving implant under 12 years of age.

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Vagus nerve stimulation for generalized epilepsy with febrile seizures plus (GEFS + ) accompanying seizures with impaired consciousness

Epilepsy & Behavior Case Reports ◽

10.1016/j.ebcr.2016.11.001 ◽

2017 ◽

Vol 7 ◽

pp. 16-19 ◽

Cited By ~ 5

Author(s):

Ryosuke Hanaya ◽

Fajar H Niantiarno ◽

Yumi Kashida ◽

Hiroshi Hosoyama ◽

Shinsuke Maruyama ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Febrile Seizures ◽

Impaired Consciousness ◽

Generalized Epilepsy ◽

Febrile Seizures Plus

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A.6 Vagus Nerve Stimulation in patients with therapy resistant generalized epilepsy

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.268 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S15-S15

Author(s):

AS Suller Marti ◽

SM Mirsattari ◽

KW MacDougall ◽

D Steven ◽

A Parrent ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Hospital Admissions ◽

Focal Epilepsy ◽

Limited Information ◽

Best Response ◽

History Of ◽

Generalized Epilepsy

Background: For patients with generalized epilepsy who do not respond to anti-seizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox Gastaut Syndrome(LGS) and genetic generalized epilepsy(GGE). Methods: We identified patients with a diagnosis of Lennox-Gastaut Syndrome or Genetic Generalized Epilepsy, who underwent VNS implantation, between1997 and July 2018. Results: A total of 46 patients were included in this study with a history of therapy resistant generalized epilepsy. The mean age at implantation was 24 years(IQR= 17.8-31 years) and 50%(n=23) were female. The most common etiologies were GGE in 37%(n=17) and LGS in 63%(n=29). Median follow-up since VNS implantation was 63 months(IQR:31-112.8months). 41.7%(n=12) of the LGS group became responders, and 64.7%(n=11) in the GGE group. The best response in seizure reduction was seen in generalized tonic-clonic seizures. There was a reduction of seizure-related hospital admissions from 89.7%(N=26) pre-implantation, to 41.4%(N=12) post-implantation (p<0.0001). The frequency of side effects due to the stimulation was similar in both groups(62.1% in LGS and 61.1% in GGE). Conclusions: VNS is an effective treatment in patients with therapy resistant generalized epilepsy, especially GGE.

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Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation (Preprint)

10.2196/preprints.20488 ◽

2020 ◽

Author(s):

Asim H Gazi ◽

Nil Z Gurel ◽

Kristine L S Richardson ◽

Matthew T Wittbrodt ◽

Amit J Shah ◽

...

Keyword(s):

Heart Rate ◽

Vagus Nerve ◽

State Space ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Closed Loop ◽

Promising Alternative ◽

Wearable Sensing ◽

Space Modeling ◽

Mean Square Errors

BACKGROUND Transcutaneous cervical vagus nerve stimulation (tcVNS) is a promising alternative to implantable stimulation of the vagus nerve. With demonstrated potential in myriad applications, ranging from systemic inflammation reduction to traumatic stress attenuation, closed-loop tcVNS during periods of risk could improve treatment efficacy and reduce ineffective delivery. However, achieving this requires a deeper understanding of biomarker changes over time. OBJECTIVE The aim of the present study was to reveal the dynamics of relevant cardiovascular biomarkers, extracted from wearable sensing modalities, in response to tcVNS. METHODS Twenty-four human subjects were recruited for a randomized double-blind clinical trial, for whom electrocardiography and photoplethysmography were used to measure heart rate and photoplethysmogram amplitude responses to tcVNS, respectively. Modeling these responses in state-space, we (1) compared the biomarkers in terms of their predictability and active vs sham differentiation, (2) studied the latency between stimulation onset and measurable effects, and (3) visualized the true and model-simulated biomarker responses to tcVNS. RESULTS The models accurately predicted future heart rate and photoplethysmogram amplitude values with root mean square errors of approximately one-fifth the standard deviations of the data. Moreover, (1) the photoplethysmogram amplitude showed superior predictability (<i>P</i>=.03) and active vs sham separation compared to heart rate; (2) a consistent delay of greater than 5 seconds was found between tcVNS onset and cardiovascular effects; and (3) dynamic characteristics differentiated responses to tcVNS from the sham stimulation. CONCLUSIONS This work furthers the state of the art by modeling pertinent biomarker responses to tcVNS. Through subsequent analysis, we discovered three key findings with implications related to (1) wearable sensing devices for bioelectronic medicine, (2) the dominant mechanism of action for tcVNS-induced effects on cardiovascular physiology, and (3) the existence of dynamic biomarker signatures that can be leveraged when titrating therapy in closed loop. CLINICALTRIAL ClinicalTrials.gov NCT02992899; https://clinicaltrials.gov/ct2/show/NCT02992899 INTERNATIONAL REGISTERED REPORT RR2-10.1016/j.brs.2019.08.002

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Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation

JMIR mhealth and uhealth ◽

10.2196/20488 ◽

2020 ◽

Vol 8 (9) ◽

pp. e20488 ◽

Cited By ~ 4

Author(s):

Asim H Gazi ◽

Nil Z Gurel ◽

Kristine L S Richardson ◽

Matthew T Wittbrodt ◽

Amit J Shah ◽

...

Keyword(s):

Heart Rate ◽

Vagus Nerve ◽

State Space ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Closed Loop ◽

Promising Alternative ◽

Wearable Sensing ◽

Space Modeling ◽

Mean Square Errors

Background Transcutaneous cervical vagus nerve stimulation (tcVNS) is a promising alternative to implantable stimulation of the vagus nerve. With demonstrated potential in myriad applications, ranging from systemic inflammation reduction to traumatic stress attenuation, closed-loop tcVNS during periods of risk could improve treatment efficacy and reduce ineffective delivery. However, achieving this requires a deeper understanding of biomarker changes over time. Objective The aim of the present study was to reveal the dynamics of relevant cardiovascular biomarkers, extracted from wearable sensing modalities, in response to tcVNS. Methods Twenty-four human subjects were recruited for a randomized double-blind clinical trial, for whom electrocardiography and photoplethysmography were used to measure heart rate and photoplethysmogram amplitude responses to tcVNS, respectively. Modeling these responses in state-space, we (1) compared the biomarkers in terms of their predictability and active vs sham differentiation, (2) studied the latency between stimulation onset and measurable effects, and (3) visualized the true and model-simulated biomarker responses to tcVNS. Results The models accurately predicted future heart rate and photoplethysmogram amplitude values with root mean square errors of approximately one-fifth the standard deviations of the data. Moreover, (1) the photoplethysmogram amplitude showed superior predictability (P=.03) and active vs sham separation compared to heart rate; (2) a consistent delay of greater than 5 seconds was found between tcVNS onset and cardiovascular effects; and (3) dynamic characteristics differentiated responses to tcVNS from the sham stimulation. Conclusions This work furthers the state of the art by modeling pertinent biomarker responses to tcVNS. Through subsequent analysis, we discovered three key findings with implications related to (1) wearable sensing devices for bioelectronic medicine, (2) the dominant mechanism of action for tcVNS-induced effects on cardiovascular physiology, and (3) the existence of dynamic biomarker signatures that can be leveraged when titrating therapy in closed loop. Trial Registration ClinicalTrials.gov NCT02992899; https://clinicaltrials.gov/ct2/show/NCT02992899 International Registered Report Identifier (IRRID) RR2-10.1016/j.brs.2019.08.002

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Closed-loop vagus nerve stimulation. Patient-tailored therapy or undirected treatment?

Interdisciplinary Neurosurgery ◽

10.1016/j.inat.2020.101003 ◽

2021 ◽

Vol 23 ◽

pp. 101003

Author(s):

Philipp Spindler ◽

Peter Vajkoczy ◽

Ulf Cristoph Schneider

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Closed Loop ◽

Tailored Therapy

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Vagus Nerve Stimulation Paired With Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools

Neurorehabilitation and Neural Repair ◽

10.1177/1545968319895480 ◽

2020 ◽

Vol 34 (3) ◽

pp. 200-209 ◽

Cited By ~ 2

Author(s):

Michael J. Darrow ◽

Miranda Torres ◽

Maria J. Sosa ◽

Tanya T. Danaphongse ◽

Zainab Haider ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vagus Nerve ◽

Motor Neurons ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Closed Loop ◽

Neurological Injury ◽

Injury Model ◽

Cord Injury

Closed-loop vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a strategy to enhance recovery after neurological injury. Previous studies demonstrate that brief bursts of closed-loop VNS paired with rehabilitative training substantially improve recovery of forelimb motor function in models of unilateral and bilateral contusive spinal cord injury (SCI) at spinal level C5/6. While these findings provide initial evidence of the utility of VNS for SCI, the injury model used in these studies spares the majority of alpha motor neurons originating in C7-T1 that innervate distal forelimb muscles. Because the clinical manifestation of SCI in many patients involves damage at these levels, it is important to define whether damage to the distal forelimb motor neuron pools limits VNS-dependent recovery. In this study, we assessed recovery of forelimb function in rats that received a bilateral incomplete contusive SCI at C7/8 and underwent extensive rehabilitative training with or without paired VNS. The study design, including planned sample size, assessments, and statistical comparisons, was preregistered prior to beginning data collection ( https://osf.io/ysvgf/ ). VNS paired with rehabilitative training significantly improved recovery of volitional forelimb strength compared to equivalent rehabilitative training without VNS. Additionally, VNS-dependent enhancement of recovery generalized to 2 similar, but untrained, forelimb tasks. These findings indicate that damage to alpha motor neurons does not prevent VNS-dependent enhancement of recovery and provides additional evidence to support the evaluation of closed-loop VNS paired with rehabilitation in patients with incomplete cervical SCI.

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