title: Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial.
abstract: BACKGROUND
  Preliminary work suggests that single-pulse transcranial magnetic stimulation (sTMS) could be effective as a treatment for migraine. We aimed to assess the efficacy and safety of a new portable sTMS device for acute treatment of migraine with aura.
  
  
  METHODS
  We undertook a randomised, double-blind, parallel-group, two-phase, sham-controlled study at 18 centres in the USA. 267 adults aged 18-68 years were enrolled into phase one. All individuals had to meet international criteria for migraine with aura, with visual aura preceding at least 30% of migraines followed by moderate or severe headache in more than 90% of those attacks. 66 patients dropped out during phase one. In phase two, 201 individuals were randomly allocated by computer to either sham stimulation (n=99) or sTMS (n=102). We instructed participants to treat up to three attacks over 3 months while experiencing aura. The primary outcome was pain-free response 2 h after the first attack, and co-primary outcomes were non-inferiority at 2 h for nausea, photophobia, and phonophobia. Analyses were modified intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00449540.
  
  
  RESULTS
  37 patients did not treat a migraine attack and were excluded from outcome analyses. 164 patients treated at least one attack with sTMS (n=82) or sham stimulation (n=82; modified intention-to-treat analysis set). Pain-free response rates after 2 h were significantly higher with sTMS (32/82 [39%]) than with sham stimulation (18/82 [22%]), for a therapeutic gain of 17% (95% CI 3-31%; p=0.0179). Sustained pain-free response rates significantly favoured sTMS at 24 h and 48 h post-treatment. Non-inferiority was shown for nausea, photophobia, and phonophobia. No device-related serious adverse events were recorded, and incidence and severity of adverse events were similar between sTMS and sham groups.
  
  
  CONCLUSIONS
  Early treatment of migraine with aura by sTMS resulted in increased freedom from pain at 2 h compared with sham stimulation, and absence of pain was sustained 24 h and 48 h after treatment. sTMS could be a promising acute treatment for some patients with migraine with aura.
  
  
  BACKGROUND
  Neuralieve.
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA rlipton@aecom.yu.edu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lipton
authors.forename: David W
authors.initials: DW
authors.lastname: Dodick
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Silberstein
authors.forename: Joel R
authors.initials: JR
authors.lastname: Saper
authors.forename: Sheena K
authors.initials: SK
authors.lastname: Aurora
authors.forename: Starr H
authors.initials: SH
authors.lastname: Pearlman
authors.forename: Robert E
authors.initials: RE
authors.lastname: Fischell
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Ruppel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000628:therapy*; D059408:Pain Management; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D014481:United States; D014796:Visual Perception; D055815:Young Adult