Blepharospasm: A genetic screening study in 132 patients.
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ABSTRACT:
SUBMITTER: Hammer M
PROVIDER: S-EPMC6739171 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Blepharospasm: A genetic screening study in 132 patients.
Hammer Monia M Abravanel Alexandra A Peckham Elizabeth E Mahloogi Ava A Majounie Elisa E Hallett Mark M Singleton Andrew A
Parkinsonism & related disorders 20190402
<h4>Introduction</h4>Blepharospasm is a common type of focal dystonia that involves involuntary eyelid spasms and eye closure. In familial cases, an autosomal dominant pattern of inheritance is noted with reduced penetrance. Few genes have been associated with the disease including GNAL and CIZ1. A whole exome sequencing study published lately suggested TOR2A and REEP4 as potential candidate genes.<h4>Methods</h4>Sanger sequencing of GNAL, CIZ1, TOR2A and REEP4 exons including exon-intron bounda ...[more]
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Project description:BACKGROUND: Benign essential blepharospasm (BEB) is a common form of focal dystonia. Besides pathology in the basal ganglia, accumulating evidence suggests pathologic changes in the anterior cingulate cortex (ACC). METHODS: This is a randomized, sham-controlled, observer-blinded prospective study. In 12 patients with BEB, we evaluated the effects of a 15-minute session of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the ACC with stimulation intensities at 100% active motor threshold with 3 stimulation coils: a conventional circular coil (C-coil), a sham coil (S-coil), and a Hesed coil (H-coil, which allows stimulation of deeper brain regions. Primary outcome was the clinical effects on BEB (blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after, and 1 hour after stimulation); secondary outcome was the blink reflex recovery curve. RESULTS: Subjective stimulation comfort was similar for each coil with no stimulation-associated adverse events. Stimulation with the H- and C-coils resulted in a significant improvement in all 3 outcome measures and was still detectable in physician rating and patient rating 1 hour after stimulation. S-coil stimulation had no effects. The active motor threshold was significantly lower for the H-coil compared to the other 2 coils. CONCLUSIONS: rTMS could be used as a therapeutic tool in BEB. Further studies will be necessary to show whether repeated stimulation applications result in lasting clinical effects. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with BEB, H- and C-coil rTMS is safe and improves clinical symptoms of BEB immediately and 1 hour after stimulation.
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Project description:ObjectiveMelanopsin may be involved in the pathophysiology of photophobia in idiopathic isolated blepharospasm. We assessed the efficacy of blocking wavelengths of melanopsin absorption to reduce blinking in blepharospasm as a possible surrogate for photophobia.MethodsTwenty-one participants (11 blepharospasm and 10 healthy controls) were studied. There were three sessions: (1) a baseline condition to measure the blink rate (BR) without intervention; (2) two conditions where the participants received intermittent light stimuli with high or low intensity without wearing study lenses; (3) four conditions in which the participants received intermittent light stimuli with high intensity while wearing one of four different lenses: tinted lenses with neutral gray or FL-41, or coated lenses that block 480-nm or 590-nm wavelength. The primary outcome measure was the BR.ResultsThe blepharospasm group blinked more frequently than controls in dim room conditions. Patients reported greater photosensitivity compared to controls based on the questionnaire and exhibited a higher BR with intermittent light stimuli. The BR decreased for both groups when using 480-nm and 590-nm blocking lenses. In the patients, 480-nm and 590-nm blocking lenses reduced the mean BR by 9.6 blink/min and 10.3 blink/min, respectively, while in the control group, the mean BR decreased by 4.4 blink/min and 4.3 blink/min, respectively.ConclusionsBlepharospasm patients had increased BR with light stimuli which decreased with 590-nm and 480-nm blocking lenses. The 480-nm- and 590-nm- coated lenses might have therapeutic potential in treating photophobia although BR does not appear to be an optimal biomarker for photophobia.
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Project description:BACKGROUND AND PURPOSE:Injectable botulinum neurotoxin (BoNT) is the principal effective treatment for blepharospasm (BSP). This trial explores the safety and efficacy of topical acetyl hexapeptide-8 (AH8), a competitive SNAP25 inhibitor, as a potential new therapy in BSP. METHODS:Double-blind, placebo-controlled, randomized trial of daily topical application of AH8 in 24 patients with BSP. The primary outcome was time to return to baseline Jankovic Blepharospasm Rating Scale (JBRS) after a BoNT injection simultaneously with the initiation of AH8. Patients displaying a strictly regular pattern of response to 3-monthly injections of BoNT were included. RESULTS:There were no significant adverse events. There was a trend for longer time until return to baseline JBRS after injection in the active group compared to placebo (3.7 months vs. 3.0 months), and for better scores in the active group. One-third (4/12) of the patients in the active group had a considerable extension of symptom control after BoNT (range: 3.3-7.1 months). CONCLUSIONS:Topical AH8 is safe and promising for extending the duration of action of BoNT therapy for BSP.
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Project description:BackgroundBlepharospasm is typically diagnosed by excluding any secondary diseases and neuropsychiatric disorders, as specific tests for blepharospasm are currently unavailable. Since anticholinergic agents are used to improve the symptoms of dystonia, we hypothesized that edrophonium chloride, an acetylcholinesterase inhibitor, may make the symptoms of dystonia more apparent. Therefore, we examined whether an edrophonium challenge test would be useful for diagnosing blepharospasm.MethodsWe studied 10 patients with blepharospasm and 10 with hemifacial spasms (as disease controls). We administered edrophonium and saline in this double-blind study. Before and after the injection, we recorded the clinical signs using a video camera to assess the objective symptoms every 2 min. Ten minutes after the isotonic sodium chloride and edrophonium injections, the patients evaluated their subjective signs using a visual analog scale (VAS). The objective signs on the video recordings were scored by specialists who were blind to the treatment.ResultsThe subjective and objective signs of the patients with blepharospasm were amplified by edrophonium. In contrast, the signs in patients with hemifacial spasms were not changed by the edrophonium challenge test.ConclusionsThe edrophonium challenge test may be used to diagnose blepharospasm. The study was registered with a ICMJE recognized registry, the UMIN-CTR, with the number UMIN000022557.
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Project description:Blepharospasm, which is the most frequent cranial dystonia, is characterized clinically by bilateral, synchronous, and symmetric involuntary orbicularis oculi muscle contractions. Assessment of motor abnormalities in patients with blepharospasm is an important issue in the clinical practice of movement disorders. This video highlights the most important aspects in the clinical evaluation of blepharospasm. We will show how we approach the main motor abnormalities related to blepharospasm. Additional features that often characterize blepharospasm, such as increased blinking, sensory tricks that can transiently improve muscle spasms, and apraxia of eyelid opening will also be discussed. Then, we will summarize the main aspects that differentiate patients with blepharospasm from other conditions characterized by eyelid disturbances. Finally, we will take into account the possible therapeutic implications of an accurate clinical examination of patients.
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