Neuropathology of blepharospasm

Abstract

Background: The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal repetitive movements or postures. In blepharospasm, the face is affected, leading to excessive eye blinking and spasms of muscles around the eyes. The pathogenesis of blepharospasm is not well understood, but several imaging studies have implied subtle structural defects in several brain regions, including the cerebellum.

Objective: To delineate cerebellar pathology in brains collected at autopsy from 7 human subjects with blepharospasm and 9 matched controls.

Methods: Sections from 3 cerebellar regions were sampled and processed using Nissl and silver impregnation stains. Purkinje neurons were the focus of the evaluation, along with as several other subtle pathological features of cerebellar dysfunction such as Purkinje neuron axonal swellings (torpedo bodies), proliferation of basket cell processes around Purkinje neurons (hairy baskets), empty baskets (missing Purkinje neurons), and displacement of cell soma from their usual location (ectopic Purkinje neurons).

Results: The results revealed a significant reduction in Purkinje neuron and torpedo body density, but no changes in any of the other measures.

Conclusions: These findings demonstrate subtle neuropathological changes similar to those reported for subjects with cervical dystonia. These findings may underly some of the subtle imaging changes reported for blepharospasm.

Figure 1.

Cerebellar neuropathologic features. Panel A shows the usual anatomical arrangement with 4 Purkinje neurons (PN) in the PN cell layer between the molecular layer (ML) and the granule cell layer (GCL). Also evident in this section is an ectopic PN in the middle of the molecular layer. Panel B also shows the PN cell layer between the ML and GCL, with a large torpedo body extending into the ML. Panel C shows the PN cell layer at higher magnification with an example of one PN and its nucleolus along with an empty basket (EB). Bar graphs at the bottom of the figure show average values ±SEM for blepharospasm (n=7, gray) and controls (n=9, black). To account for differences in tissue section sizes, all histopathological features counted were normalized according to length of the Purkinje neuron layer measured, and expressed as linear density (items/mm). Double asterisk denotes p<0.005, and single asterisk denotes p<0.02 in linear regression analyses.

Figure 2.

Cerebellar hairy baskets. The left side of the figure provides examples of hairy basket severity where individual Purkinje neurons are associated with few or no stained fibers (HB1), a few fibers close to the soma (HB2), a more extensive fiber network nearly surrounding the soma (HB3), and a fiber network nearly encasing the soma (HB4). The distribution of severity appeared to be shifted to the left (less severe) in blepharospasm cases compared to controls, but the difference was not statistically significant.