Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy

PLoS One. 2016 Dec 16;11(12):e0168652. doi: 10.1371/journal.pone.0168652. eCollection 2016.


Objective: Benign Essential Blepharospasm (BEB) and hemifacial spasm (HFS) are the most common hyperkinetic movement disorders of facial muscles. Although similar in clinical presentation different pathophysiological mechanisms are assumed. Botulinum Neurotoxin (BoNT) is a standard evidence-based treatment for both conditions. In this study we aimed to assess grey matter microstructural differences between these two groups of patients and compared them with healthy controls. In patients we furthermore tracked the longitudinal morphometric changes associated with BoNT therapy. We hypothesized microstructural differences between the groups at the time point of maximum symptoms representation and distinct longitudinal grey matter dynamics with symptom improvement.

Methods: Cross-sectional and longitudinal analyses of 3T 3D-T1 MRI images from BEB, HFS patients prior to and one month after BoNT therapy and from a group of age and sex matched healthy controls. Cortical thickness as extracted from Freesurfer was assessed as parameter of microstructural integrity.

Results: BoNT therapy markedly improved motor symptoms in patients with BEB and HFS. Significant differences of grey matter integrity have been found between the two patients groups. The BEB group showed lower cortical thickness at baseline in the frontal-rostral, supramarginal and temporal regions compared to patients with HFS. In this group BoNT treatment was associated with a cortical thinning in the primary motor cortex and the pre-supplementary motor area (pre-SMA). Contrary patients with HFS showed no longitudinal CT changes. A decreased cortical thickness was attested bilaterally in the temporal poles and in the right superior frontal region in BEB patients in comparison to HC. Patients in the HFS group presented a decreased CT in the left lingual gyrus and temporal pole.

Conclusions: Although patients with BEB and HFS present clinically with involuntary movements of facial muscles, they exhibited differences in cortical thickness. While BoNT therapy was equally effective in both groups, widespread changes of cortical morphology occurred only in BEB patients. We demonstrated specific disease- and therapy-dependent structural changes induced by BoNT in the studied hyperkinetic conditions.

MeSH terms

  • Adult
  • Aged
  • Blepharospasm / diagnostic imaging
  • Blepharospasm / drug therapy*
  • Botulinum Toxins / administration & dosage*
  • Botulinum Toxins / pharmacology
  • Cross-Sectional Studies
  • Female
  • Gray Matter / diagnostic imaging*
  • Gray Matter / drug effects
  • Hemifacial Spasm / diagnostic imaging
  • Hemifacial Spasm / drug therapy*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Treatment Outcome


  • Botulinum Toxins

Supplementary concepts

  • Benign essential blepharospasm

Grant support

This work was supported by the German Research Council (CRC 1193, project B05). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.