title: The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial.
abstract: OBJECTIVE
  To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long-term health-related quality of life (HRQoL).
  
  
  METHODS
  PuLsE (Open Prospective Randomized Long-term Effectiveness) was a prospective, randomized, parallel-group, open-label, and long-term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n = 112) received VNS + BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory-89 total score; QOLIE-89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES-D), Neurological Disorders Depression Inventory-Epilepsy scale (NDDI-E), Clinical Global Impression-Improvement scale (CGI-I), Adverse Event Profile (AEP), and antiepileptic drug (AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n = 362. Results for n = 96 who had baseline and at least one follow-up QOLIE-89 assessment (from months 3-12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints.
  
  
  RESULTS
  Significant between-group differences in favor of VNS + BMP were observed regarding improvement in HRQoL, seizure frequency, and CGI-I score (respective p-values < 0.05, 0.03, and 0.01). More patients in the VNS + BMP group (43%) reported adverse events (AEs) versus BMP group (21%) (p = 0.01), a difference reflecting primarily mostly transient AEs related to VNS implantation or stimulation. No significant difference between treatment groups was observed for changes in CES-D, NDDI-E, AEP, and AED load.
  
  
  CONCLUSIONS
  VNS therapy as a treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant improvement in HRQoL compared with BMP alone. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
authors.affiliation: TIGER, CRNL, INSERM U1028, CNRS 5292 and Hospices Civils de Lyon and Claude Bernard Lyon-1 University, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
authors.forename: Frank G
authors.initials: FG
authors.lastname: Gilliam
authors.forename: Dang K
authors.initials: DK
authors.lastname: Nguyen
authors.forename: Gabriella
authors.initials: G
authors.lastname: Colicchio
authors.forename: Alfonso
authors.initials: A
authors.lastname: Iudice
authors.forename: Paolo
authors.initials: P
authors.lastname: Tinuper
authors.forename: Nelia
authors.initials: N
authors.lastname: Zamponi
authors.forename: Umberto
authors.initials: U
authors.lastname: Aguglia
authors.forename: Louis
authors.initials: L
authors.lastname: Wagner
authors.forename: Lorella
authors.initials: L
authors.lastname: Minotti
authors.forename: Hermann
authors.initials: H
authors.lastname: Stefan
authors.forename: Paul
authors.initials: P
authors.lastname: Boon
authors.forename: Mark
authors.initials: M
authors.lastname: Sadler
authors.forename: Paolo
authors.initials: P
authors.lastname: Benna
authors.forename: Pradheep
authors.initials: P
authors.lastname: Raman
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D004351:Drug Resistance; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000523:psychology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life / Q000523:psychology*; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000927:Anticonvulsants
keywords: Epilepsy; Health-related quality of life; QOLIE-89; Seizures; Vagus nerve stimulation
references.citation: Neurology. 2004 Jan 13;62(1):23-7
references.pmid: 14718691
references.citation: Cir Cir. 2010 Jan-Feb;78(1):15-23, 24
references.pmid: 20226124
references.citation: Childs Nerv Syst. 2011 May;27(5):787-92
references.pmid: 21038079
references.citation: Epilepsia. 2011 Dec;52(12):2181-91
references.pmid: 22136077
references.citation: Epilepsy Behav. 2011 Mar;20(3):478-83
references.pmid: 21296622
references.citation: Neurology. 2002 Sep 24;59(6 Suppl 4):S26-30
references.pmid: 12270965
references.citation: Epilepsia. 2009 May;50(5):1220-8
references.pmid: 19170732
references.citation: Epilepsia. 2002 May;43(5):535-8
references.pmid: 12027916
references.citation: N Engl J Med. 2011 Sep 8;365(10):919-26
references.pmid: 21899452
references.citation: Clin Neurol Neurosurg. 2012 May;114(4):336-40
references.pmid: 22130047
references.citation: Epilepsy Behav. 2011 Jan;20(1):57-63
references.pmid: 21144802
references.citation: Epilepsia. 2010 May;51(5):797-804
references.pmid: 20545754
references.citation: Eur Neurol. 2003;50(1):16-9
references.pmid: 12824707
references.citation: Qual Life Res. 2006 Jun;15(5):899-914
references.pmid: 16721649
references.citation: Lancet Neurol. 2010 Jan;9(1):27-9
references.pmid: 19914135
references.citation: Lancet Neurol. 2006 May;5(5):399-405
references.pmid: 16632310
references.citation: Epilepsia. 1995 Nov;36(11):1089-104
references.pmid: 7588453
references.citation: Epileptic Disord. 2011 Dec;13(4):382-8
references.pmid: 22258042
references.citation: Neurology. 1999 Nov 10;53(8):1731-5
references.pmid: 10563620
references.citation: Neurology. 2011 Jan 18;76(3):273-9
references.pmid: 21242496