title: Blepharospasm and the modulation of cortical excitability in primary and secondary motor areas.
abstract: BACKGROUND
  Traditionally, benign essential blepharospasm (BEB) is considered a disorder caused by basal ganglia dysfunction. Electrophysiologic and brain imaging studies suggest pathologic changes in excitability in the primary motor cortex (MC), anterior cingulate (AC), and secondary motor areas, such as premotor (PMC) and supplementary motor cortices (SMA).
  
  
  METHODS
  In this pilot study of 7 patients with BEB, we experimentally reduced cortical excitability of 4 areas: MC (first dorsal interosseus area), PMC, SMA, and AC, each with 3 noninvasive techniques: low-frequency repetitive transcranial magnetic stimulation (lfrTMS), continuous theta burst stimulation (cTBS), and cathodal transcranial direct current stimulation (tDCS). Primary outcome was the clinical effects on blepharospasm (blink rate observation by an investigator blinded to the intervention and subjective rating by the patient); secondary outcome was the blink reflex recovery curve (BRR).
  
  
  RESULTS
  lfrTMS resulted in a significant improvement over all 4 brain areas for physician rating, patient rating, and BRR, whereas cTBS and tDCS showed only trends for improvement in physician rating, but no improvements for patient rating and BRR. lfrTMS had a significantly higher effect over AC than MC for physician rating, but no differences were seen for other pairwise comparisons of stimulated brain areas.
  
  
  CONCLUSIONS
  Electrophysiologic and clinical improvements by functional inhibition of the medial frontal areas using low-frequency repetitive transcranial magnetic stimulation suggests that hypersensitivity of the anterior cingulate is directly or indirectly involved in the pathophysiology of benign essential blepharospasm. Inhibition of these areas using low-frequency repetitive transcranial magnetic stimulation could provide a therapeutic tool and is worthy of a larger study.
authors.affiliation: Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. gottfried.kranz@meduniwien.ac.at
authors.forename: G
authors.initials: G
authors.lastname: Kranz
authors.forename: E A
authors.initials: EA
authors.lastname: Shamim
authors.forename: P T
authors.initials: PT
authors.lastname: Lin
authors.forename: G S
authors.initials: GS
authors.lastname: Kranz
authors.forename: B
authors.initials: B
authors.lastname: Voller
authors.forename: M
authors.initials: M
authors.lastname: Hallett
mesh_terms: D000368:Aged; D001764:Blepharospasm / Q000175:diagnosis* / Q000503:physiopathology*; D001767:Blinking / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000502:physiology*; D010865:Pilot Projects; D011446:Prospective Studies; D016037:Single-Blind Method; D050781:Transcranial Magnetic Stimulation / Q000379:methods