title: Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke.
abstract: OBJECTIVE
  Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke.
  
  
  METHODS
  Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl-Meyer Assessment-Upper Extremity).
  
  
  RESULTS
  Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, -0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6).
  
  
  CONCLUSIONS
  This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed.
  
  
  BACKGROUND
  URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161.
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.). jesse.dawson@glasgow.ac.uk.
authors.forename: Jesse
authors.initials: J
authors.lastname: Dawson
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: David
authors.initials: D
authors.lastname: Pierce
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Anand
authors.initials: A
authors.lastname: Dixit
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Teresa J
authors.initials: TJ
authors.lastname: Kimberley
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Michele
authors.initials: M
authors.lastname: Robertson
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Brent
authors.initials: B
authors.lastname: Tarver
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Omar
authors.initials: O
authors.lastname: Hilmi
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: John
authors.initials: J
authors.lastname: McLean
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Kirsten
authors.initials: K
authors.lastname: Forbes
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kilgard
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Robert L
authors.initials: RL
authors.lastname: Rennaker
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Steven C
authors.initials: SC
authors.lastname: Cramer
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Walters
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (J.D., M.W.) and Robertson Centre for Biostatistics (M.R.), University of Glasgow, Western Infirmary, Glasgow, United Kingdom; MicroTransponder, Inc., Austin, TX (D.P.); University of Texas at Dallas, Richardson (D.P., B.T., N.E.); Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom (A.D.); Programs in Physical Therapy and Rehabilitation Science, Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis (T.J.K.); Department of Otolaryngology, Glasgow Royal Infirmary (O.H.) and Neuroradiology, Institute of Neurological Sciences, NHS (J.M., K.F.), Greater Glasgow and Clyde, Glasgow, United Kingdom; School of Behavioral and Brain Sciences (M.P.K., R.L.R.) and Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science (M.P.K.), University of Texas at Dallas, Richardson; and the Sue & Bill Gross Stem Cell Research Center, and Departments of Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, University of California, Irvine (S.C.C.).
authors.forename: Navzer
authors.initials: N
authors.lastname: Engineer
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000150:complications / Q000175:diagnosis / Q000534:rehabilitation*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000175:diagnosis / Q000209:etiology / Q000534:rehabilitation*; D061214:Patient Safety; D010865:Pilot Projects; D020127:Recovery of Function; D016037:Single-Blind Method; D020521:Stroke / Q000150:complications / Q000175:diagnosis; D000071939:Stroke Rehabilitation; D016896:Treatment Outcome; D034941:Upper Extremity / Q000473:pathology; D055536:Vagus Nerve Stimulation / Q000009:adverse effects / Q000639:trends*
keywords: deglutition disorders; intention to treat analysis; rehabilitation; stroke; vagus nerve