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.

Figure 1 Comparison of the 3 stimulation techniques X-axis: stimulation techniques, tDCS = transcranial direct current stimulation; cTBS = continuous theta burst stimulation; lfrTMS = repetitive low-frequency transcranial magnetic stimulation; Y-axis: percent change before and after stimulation; BRR = blink reflex recovery; PhysR = physician rating; PatR = patient rating. Error bars represent standard errors for the estimated least-squares means.

Figure 2 Stimulation effects over the frontal (supplementary motor cortex/anterior cingulate) and dorsal (motor cortex/premotor cortex) brain areas for the 3 outcome measures X-axis: outcome measures; BRR = blink reflex recovery; PhysR = physician rating; PatR = patient rating; Y-axis: percent change before and after stimulation. Error bars represent standard errors for the estimated least-squares means.

Figure 3 Comparison of the 4 brain areas (motor cortex/premotor cortex/supplementary motor cortex/anterior cingulate): Stimulation with lfrTMS X-axis: outcome measures; BRR = blink reflex recovery; PhysR = physician rating; PatR = patient rating; Y-axis: percent change before and after stimulation. Error bars represent standard errors for the estimated least-squares means.