title: Cervical non-invasive vagus nerve stimulation (nVNS) for preventive and acute treatment of episodic and chronic migraine and migraine-associated sleep disturbance: a prospective observational cohort study.
abstract: BACKGROUND
  The debilitating nature of migraine and challenges associated with treatment-refractory migraine have a profound impact on patients. With the need for alternatives to pharmacologic agents, vagus nerve stimulation has demonstrated efficacy in treatment-refractory primary headache disorders. We investigated the use of cervical non-invasive vagus nerve stimulation (nVNS) for the acute treatment and prevention of migraine attacks in treatment-refractory episodic and chronic migraine (EM and CM) and evaluated the impact of nVNS on migraine-associated sleep disturbance, disability, and depressive symptoms.
  
  
  METHODS
  Twenty patients with treatment-refractory migraine were enrolled in this 3-month, open-label, prospective observational study. Patients administered nVNS prophylactically twice daily at prespecified times and acutely as adjunctive therapy for migraine attacks. Pain intensity (visual analogue scale [VAS]); number of headache days per month and number of migraine attacks per month; number of acutely treated attacks and time to achieve pain relief; sleep quality (Pittsburgh Sleep Quality Index [PSQI]); migraine disability assessment (MIDAS); depressive symptoms (Beck Depression Inventory(®) [BDI]); and adverse events (AEs) were evaluated.
  
  
  RESULTS
  Of the 20 enrolled patients, 10 patients each had been diagnosed with EM and CM. Prophylaxis with nVNS was associated with significant overall reductions in patient-perceived pain intensity (mean VAS scores at baseline vs 3 months: 7.75 ± 0.64 vs 4.05 ± 0.76; 95 % CI: 3.3, 4.1; p < 0.0001), mean number of headache days per month (baseline vs 3 months: 14.7 ± 4.1 vs 8.9 ± 3.66; 95 % CI: 3.3, 8.3; p < 0.0001), and mean number of migraine attacks per month (baseline vs 3 months: 7.3 ± 3.85 vs 4.45 ± 2.48; 95 % CI: 0.8, 4.9; p < 0.01). For acutely treated migraine attacks, a reduction in mean time (minutes) to achieve pain relief (baseline vs 3 months: 84.5 ± 39.1 vs 52.75 ± 16.42; 95 % CI: 12.6, 51.0; p < 0.002) was noted. Significant improvements, more evident in patients with EM, were noted in MIDAS and BDI scores along with a trend toward improvement in PSQI daytime dysfunction subscore (p = 0.07). No severe or serious AEs occurred.
  
  
  CONCLUSIONS
  In this study, treatment with nVNS was safe and provided clinically meaningful decreases in the frequency, intensity, and duration of migraine attacks in patients with treatment-refractory migraine. Improvements in migraine-associated disability, depression, and sleep quality were also noted.
authors.affiliation: Division of Functional Neurosurgery and Neuromodulation, Rheinische Friedrich-Wilhelms University, Regina-Pacis-Weg 3, 53113, Bonn, Germany. thomas.kinfe@ukb.uni-bonn.de.|Department of Neurosurgery, Rheinische Friedrich-Wilhelms University, Regina-Pacis-Weg 3, 53113, Bonn, Germany. thomas.kinfe@ukb.uni-bonn.de.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kinfe
authors.affiliation: Department of Neurosurgery, Rheinische Friedrich-Wilhelms University, Regina-Pacis-Weg 3, 53113, Bonn, Germany. bogdan.pintea@ukb.uni-bonn.de.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Pintea
authors.affiliation: Department of Neurosurgery, Rheinische Friedrich-Wilhelms University, Regina-Pacis-Weg 3, 53113, Bonn, Germany. sajjad.muhammad@ukb.uni-bonn.de.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Muhammad
authors.affiliation: Sleep Medicine, Department of Neurology, Rheinische Friedrich-Wilhelms University, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany. sebastian.zaremba@ukb.uni-bonn.de.|Department of Clinical Research, German Centre for Neurodegenerative Diseases (DZNE), Ernst-Robert-Curtius-Str. 12, 53117, Bonn, Germany. sebastian.zaremba@ukb.uni-bonn.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zaremba
authors.affiliation: Department of Clinical Research, German Centre for Neurodegenerative Diseases (DZNE), Ernst-Robert-Curtius-Str. 12, 53117, Bonn, Germany. sandra.roeske@dzne.de201.
authors.forename: Sandra
authors.initials: S
authors.lastname: Roeske
authors.affiliation: electroCore, LLC, 150 Allen Road, Suite 201, Basking Ridge, NJ, 07920, USA. bruce.simon@electrocorellc.com.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Simon
authors.affiliation: Department of Neurosurgery, Rheinische Friedrich-Wilhelms University, Regina-Pacis-Weg 3, 53113, Bonn, Germany. hartmut.vatter@ukb.uni-bonn.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Vatter
mesh_terms: D000328:Adult; D000368:Aged; D002574:Cervical Vertebrae; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000453:epidemiology* / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods*; D011446:Prospective Studies; D012893:Sleep Wake Disorders / Q000453:epidemiology* / Q000517:prevention & control*; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*
keywords: Acute therapy; Headache; Neuromodulation; Prophylactic therapy; Sleep impairment