Clinical Features and Evolution of Blepharospasm: A Multicenter International Cohort and Systematic Literature Review

Abstract

Objective: Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study was to provide a comprehensive picture of its clinical features including presenting features, motor features, and non-motor features.

Methods: This was a two-part study. The first part involved a systematic literature review that summarized clinical features for 10,324 cases taken from 41 prior reports. The second part involved a summary of clinical features for 884 cases enrolled in a large multicenter cohort collected by the Dystonia Coalition investigators, along with an analysis of the factors that contribute to the spread of dystonia beyond the periocular region.

Results: For cases in the literature and the Dystonia Coalition, blepharospasm emerged in the 50s and was more frequent in women. Many presented with non-specific motor symptoms such as increased blinking (51.9%) or non-motor sensory features such as eye soreness or pain (38.7%), photophobia (35.5%), or dry eyes (10.7%). Non-motor psychiatric features were also common including anxiety disorders (34-40%) and depression (21-24%). Among cases presenting with blepharospasm in the Dystonia Coalition cohort, 61% experienced spread of dystonia to other regions, most commonly the oromandibular region and neck. Features associated with spread included severity of blepharospasm, family history of dystonia, depression, and anxiety.

Conclusions: This study provides a comprehensive summary of motor and non-motor features of blepharospasm, along with novel insights into factors that may be responsible for its poor diagnostic recognition and natural history.

Keywords: Blepharospasm; Dystonia; Meige syndrome; Oromandibular dystonia; eyes; jaw; phenotype.

FIGURE 1 ∣

PRISMA flow diagram for literature review.

FIGURE 2 ∣

Sex and Age at Onset. (A) shows the percentage of females for all publications reaching criteria for inclusion in the literature review. The sex ratio in each study is represented by a filled circle. The open circle shows the sex ratio in the Dystonia Coalition cohort. The box shows the interquartile range of all studies, with the bar in the middle showing the median. Error bars show the full spread of data across all studies. (B) shows the mean age at onset in blepharospasm. This plot shows the average (filled circles) and standard deviation (error bars) for all publications reaching criteria for inclusion in the literature review. It also shows the average (open circle) and standard deviation for the Dystonia Coalition cohort.

FIGURE 3 ∣

Motor and non-motor features of blepharospasm. These plots illustrate (A) clinician reported motor features, (B) subject reported motor features, and (C) subject reported sensory symptoms for both focal blepharospasm (dark bars) and blepharospasm (light bars) with subsequent spread of dystonia to other body regions. These data were derived from the subgroup of 155 subjects who participated in a blepharospasm rating scales project.