Jankovic Rating Scale Research Articles

Excessive daytime sleepiness in idiopathic blepharospasm

ObjectiveTo explore the frequency of excessive daytime sleepiness (EDS), and its impact on quality of life and its associated clinical factors in idiopathic blepharospasm. MethodsThis cross-sectional study was carried out in 425 idiopathic blepharospasm patients and a group of 424 age-matched and sex-matched healthy subjects. EDS was assessed with the Epworth Sleepiness Scale (ESS) in all subjects. Other clinical characteristics of patients with idiopathic blepharospasm including motor symptoms, sleep quality, depression, anxiety, cognition, and quality of life were also assessed. ResultsEDS was significantly more frequent in patients with idiopathic blepharospasm than in controls (22.1% vs 12.3%; p < 0.05). Blepharospasm patients with EDS scored significantly higher in Jankovic Rating scale, Hamilton Rating Scale for Depression (HDRS), Hamilton Rating Scale for Anxiety (HARS), and significantly lower in Montreal Cognitive Assessment (MoCA) and 36-Item Short Form Health Survey (SF-36) than those without EDS (p < 0.05). The binary logistic regression model indicated that male, younger age of onset of blepharospasm, higher motor scores, higher HDRS scores, and lower MoCA scores were associated with the presence of EDS in patients with blepharospasm (p < 0.05). ConclusionsRecognition and management of EDS in idiopathic blepharospasm patients is necessary as the occurrence of EDS was associated with higher motor burden, more serious mood and cognitive disturbances, and poorer quality of life. Our results suggest that blepharospasm may exhibit abnormal sleep-wake patterns and further support the clinical heterogeneity of the disease.

Machine Learning for Predicting Individual Severity of Blepharospasm Using Diffusion Tensor Imaging.

Accumulating diffusion tensor imaging (DTI) evidence suggests that white matter abnormalities evaluated by local diffusion homogeneity (LDH) or fractional anisotropy (FA) occur in patients with blepharospasm (BSP), both of which are significantly correlated with disease severity. However, whether the individual severity of BSP can be identified using these DTI metrics remains unknown. We aimed to investigate whether a combination of machine learning techniques and LDH or FA can accurately identify the individual severity of BSP. Forty-one patients with BSP were assessed using the Jankovic Rating Scale and DTI. The patients were assigned to non-functionally and functionally limited groups according to their Jankovic Rating Scale scores. A machine learning scheme consisting of beam search and support vector machines was designed to identify non-functionally versus functionally limited outcomes, with the input features being LDH or FA in 68 white matter regions. The proposed machine learning scheme with LDH or FA yielded an overall accuracy of 88.67 versus 85.19% in identifying non-functionally limited versus functionally limited outcomes. The scheme also identified a sensitivity of 91.40 versus 85.87% in correctly identifying functionally limited outcomes, a specificity of 83.33 versus 83.67% in accurately identifying non-functionally limited outcomes, and an area under the curve of 93.7 versus 91.3%. These findings suggest that a combination of LDH or FA measurements and a sophisticated machine learning scheme can accurately and reliably identify the individual disease severity in patients with BSP.

Impact of Upper Eyelid Surgery on Symptom Severity and Frequency in Benign Essential Blepharospasm.

Objective To assess the impact of periocular surgery, other than orbicularis stripping, on the severity and frequency of blepharospasm symptoms.Methods Consecutive patients with benign essential blepharospasm (BEB) who underwent eyelid/eyebrow surgery with the aim of improving symptoms were retrospectively reviewed over a 5-year period. Patients who had completed the Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BDI) pre- and at least 3 months postoperatively were included.Results Twenty-four patients were included. JRS scores significantly improved from 7.0 preoperatively to 4.1 postoperatively (p < 0.001), and BDI scores significantly improved from 18.4 preoperatively to 12.7 postoperatively (p < 0.001); the mean percentage improvements were 41% and 30%, respectively. Patients were followed for a median of 24 months postoperatively.Conclusion Periocular surgery significantly reduced BEB symptoms in the majority (83%) of patients by an average of 33% and may therefore be offered for suitable patients. An important minority (17%) of patients experienced symptom worsening.

Botulinum toxin type A therapy for blepharospasm.

This is an update of a Cochrane Review first published in 2005. Blepharospasm is the second most common form of focal dystonia. It is a disabling disorder, characterised by chronic, intermittent or persistent, involuntary eyelid closure, due to spasmodic contractions of the orbicularis oculi muscles. Currently, botulinum toxin type A (BtA) is considered the first line of therapy for this condition. To compare the efficacy, safety, and tolerability of BtA versus placebo in people with blepharospasm. We searched Cochrane Movement Disorders' Trials Register, CENTRAL, MEDLINE, Embase, reference lists of included articles, and conference proceedings. We ran all elements of the search, with no language restrictions, in July 2020. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with blepharospasm. Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus, or by consulting a third review author. We performed meta-analyses using a random-effects model, for the comparison of BtA versus placebo, to estimate pooled effects and corresponding 95% confidence intervals (95% CI). We did not carry out any prespecified subgroup analyses. The primary efficacy outcome was improvement on any validated symptomatic rating scale. The primary safety outcome was the proportion of participants with any adverse event. We included three RCTs, assessed at low to moderate overall risk of bias, which randomised 313 participants with blepharospasm. Two studies excluded participants with poorer prior responses to BtA treatment, therefore, they included an enriched population with a higher probability of benefiting from this therapy. All trials were industry-funded. All RCTs evaluated the effect of a single BtA treatment session. BtA resulted in a moderate to large improvement in blepharospasm-specific severity, with a reduction of 0.93 points on the Jankovic Rating Scale (JRS) severity subscale at four to six weeks after injection (95% confidence interval (CI) 0.61 to 1.25; I² = 9%) compared to placebo. BtA was also resulted in a moderate to large improvement in blepharospasm-specific disability and blepharospasm-specific involuntary movements at four to six weeks after injection (disability: 0.69 JRS disability subscale points, 95% CI 0.18 to 1.19; I² = 74%; blepharospasm-specific involuntary movements: standardised mean difference (SMD) 0.79, 0.31 to 1.27; I² = 58%) compared to placebo. BtA did not show a risk of adverse events (risk ratio (RR) 1.18, 95% CI 0.87 to 1.60; I² = 0%). However, BtA increased the risk of vision complaints and eyelid ptosis (vision complaints: RR 5.73, 95% CI 1.79 to 18.36; I² = 51%; eyelid ptosis: RR 4.02, 95% CI 1.61 to 10.00; I² = 39%). There was no distinction between BtA and placebo in the number of participants who dropped out of the trial. A single trial estimated the duration of effects to be 10.6 weeks (range 6.1 to 19.1). We found no evidence supporting the existence of a clear dose-response relationship with BtA. We found no data reporting the impact of BtA on health-related quality of life, or the development of secondary non-responsiveness. We are moderately certain that a single BtA treatment resulted in a clinically relevant reduction of blepharospasm-specific severity and disability, and have low certainty that it is well tolerated, when compared with placebo. There is low-certainty evidence that people treated with BtA are not at an increased risk of developing adverse events, though BtA treatment likely increases the risk of visual complaints and eyelid ptosis. There are no data from RCTs evaluating the effectiveness and safety of repeated BtA injection cycles. There is no evidence from RCTs to allow us to draw definitive conclusions on the optimal treatment intervals and doses, or the impact on quality of life.

Structural Brain Changes in Blepharospasm: A Cortical Thickness and Diffusion Tensor Imaging Study.

White matter abnormalities in blepharospasm (BSP) have been evaluated using conventional intra-voxel metrics, and changes in patterns of cortical thickness in BSP remain controversial. We aimed to determine whether local diffusion homogeneity, an inter-voxel diffusivity metric, could be valuable in detecting white matter abnormalities for BSP; whether these changes are related to disease features; and whether cortical thickness changes occur in BSP patients. Diffusion tensor and structural magnetic resonance imaging were collected for 29 patients with BSP and 30 healthy controls. Intergroup diffusion differences were compared using tract-based spatial statistics analysis and measures of cortical thickness were obtained. The relationship among cortical thickness, diffusion metric in significantly different regions, and behavioral measures were further assessed. There were no significant differences in cortical thickness and fractional anisotropy between the groups. Local diffusion homogeneity was higher in BSP patients than controls, primarily in the left superior longitudinal fasciculus, corpus callosum, left posterior corona radiata, and left posterior thalamic radiata (P < 0.05, family-wise error corrected). The local diffusion homogeneity values in these regions were positively correlated with the Jankovic rating scale (rs = 0.416, P = 0.031) and BSP disability index (rs = 0.453, P = 0.018) in BSP patients. These results suggest that intra- and inter-voxel diffusive parameters are differentially sensitive to detecting BSP-related white matter abnormalities and that local diffusion homogeneity might be useful in assessing disability in BSP patients.

IncobotulinumtoxinA for the Treatment of Blepharospasm in Toxin-Naïve Subjects: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial.

This study aimed to assess the efficacy/safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH) in botulinum neurotoxin-naïve subjects with blepharospasm. Botulinum neurotoxin-naïve subjects (≥ 12months without botulinum neurotoxin treatment for blepharospasm) received single-dose incobotulinumtoxinA 50 U, 25U, or placebo. Subjects were followed for 6-20weeks (main period). Qualified subjects entered an open-label extension period and received another incobotulinumtoxinA injection (≤ 70 U). The primary efficacy variable was change from baseline in the Jankovic Rating Scale (JRS) severity subscore at the main period of week 6. Other efficacy variables included changes in the Blepharospasm Disability Index score and JRS frequency subscore and sumscore. Adverse events were monitored. Sixty-one subjects were randomized (main period: incobotulinumtoxinA 50 U, n = 19; incobotulinumtoxinA 25 U, n = 22; placebo, n = 20); 39 entered the open-label extension period (9, 14, and 16 subjects from the incobotulinumtoxinA 50 U, incobotulinumtoxinA 25 U, and placebo groups [main period], respectively, changed to open-label extension period dosing). A statistically significantly greater reduction in JRS severity subscore was reported for subjects receiving incobotulinumtoxinA 50 U versus placebo (ANCOVA, least square mean difference: -1.2, p = 0.0004). Subjects receiving incobotulinumtoxinA experienced improvements in other efficacy variables versus baseline and/or placebo. Sustained clinical improvements and low adverse event rates (22.2-42.1%) were observed. This is the second placebo-controlled, double-blind study that demonstrates favorable efficacy/safety of incobotulinumtoxinA in subjects with blepharospasm. IncobotulinumtoxinA is the first botulinum neurotoxin that could fulfill the American Academy of Neurology criteria for a Level A recommendation for blepharospasm.Trial registration ClinicalTrials.gov identifier, NCT01896895.

Botulinum toxin for benign essential blepharospasm: A systematic review and an algorithmic approach.

Currently, there is no standardised approach for benign essential blepharospasm treatment with botulinum toxin, and controversies still exist regarding this subject. The objective of this systematic review is to summarise and compare all the published data regarding benign essential blepharospasm treatment with botulinum toxin. On October 3, 2018, an online search of the Medline database was conducted. All articles with a detailed description of their botulinum toxin injection technique for benign essential blepharospasm were included in this review. Five studies were selected for inclusion with a total of 854 patients. Four of the included studies used onabotulinumtoxin A and one study used abobotulinumtoxin A. All studies injected the pretarsal orbicularis occuli muscle. The preseptal orbicularis occuli was injected in four studies, and the preorbital muscle in three studies. The most commonly used method of evaluation was the Jankovic Rating Scale. Adverse events were transient, and dose related. Ptosis was more frequently encountered with the preseptal orbicularis injections. Botulinum toxin injection for benign essential blepharospasm is a non-invasive and safe procedure.The pretarsal muscle should be considered as the key component when treating benign essential blepharospasm with botulinum toxin.We developed an algorithmic approach to the treatment of benign essential blepharospasm with botulinum toxin.However,further randomised controlled trials are warranted.

Evaluation of botulinum toxin effects in hemifacial spasm patients: correlation between clinical rating scales and high-speed video system measurements.

The purpose of this study was to compare the scores of two clinical rating scales and high-speed video system measurements obtained during spontaneous eyelid movements in hemifacial spasm (HFS) patients before and after treatment. Patients were evaluated before and 30days after receiving treatment with onabotulinumtoxinA injections. Using a high-speed video system, the eyelid movements were recorded bilaterally for 3min and the energy power generated by the upper eyelid during spontaneous eyelid movements was assessed before and after treatment. The scores of the Jankovic rating scale (JRS) and Hemifacial Spasm Grading System (HSGS) were also assessed before and after treatment. The authors studied 22 patients. Significant reduction in JRS and HSGS scores and in the energy generated by the upper eyelid was observed after treatment. A power spectrum of less than 23,000 was associated with JRS and HSGS scores less than 4 and 6.25, respectively and a power spectrum greater than or equal to 23,000 was associated with JRS and HSGS scores greater than or equal to 4 and 6.25, respectively (p < 0.0001 and p = 0.0025). Rating systems are easy to use, but they may exhibit limitations in sensitivity to assess differences between distinct disease patterns and between subtle differences in treatment responses. The high-speed video system permits a greater degree of accuracy, which allows for the assessment of differences in eyelid movement patterns and would permit better tailoring of treatment to patients. However, simpler devices employing this system would need to be developed, so that it could be used in clinical practice.

Functional blindness: Blepharospasm with apraxia of eyelid opening

Purpose: The purpose was to evaluate the effectiveness of protractor myectomy surgery in patients with severe blepharospasm whose daily life is severely impaired. Materials and Methods: Records of fifty patients with benign, essential blepharospasm were examined retrospectively and seven were included in the study. All patients underwent a complete ophthalmological and neurological examination. The severity and frequency of spasm was determined by Jankovic Rating Scale, ranging from 0 to 4, and six daily activities were determined by Blepharospasm Disability Index. The primary indication for protractor myectomy was poor response to serial botulinum toxin injections. The main outcome measure was based on whether the spasms were fully healed or the need for additional botox application. Results: Fourteen eyes of seven patients with significant functional disability were included in the study. Excessive blinking and visual disability were the most common symptoms seen in all patients, and all had previously used one or more medications. Myectomy surgery was performed in all patients who were resistant to serial botulinum toxin injections. Of the 14 eyelids, 85.7% showed resolution of spasms and no longer required botulinum toxin treatment following surgery. One patient with keratitis sequelae and dry eye was given botulinum 1 month after the surgery. One patient with residual blepharospasm in the lower eyelid underwent lower eyelid myectomy and blepharoplasty. Transient periorbital edema, hematoma, and echymosis developed following surgery. The patients were followed up for 2 years, and excellent cosmetic result with no contracture was observed in all patients. Conclusion: Protractor myectomy is an effective treatment modality in cases of blepharospasm with severe functional disability.

Sensory Trick Frames: A New Device for Blepharospasm Patients.

ObjectiveTo determine whether the use of unique customized spectacles provided with modified side arms may be helpful in reducing benign essential blepharospasm (BEB) in patients describing periocular sensory tricks (ST).MethodsA prospective descriptive study of patients with BEB with positive periocular or temporal region ST phenomenon response under the care of the Botox Clinic at Moorfields Eye Hospital, London, UK. Nine consecutive patients with BEB describing ST were recruited, and the disease frequency and severity were assessed with the Jankovic Rating Scale (JRS) and the Blepharospasm Disability Index (BSDI) before and after the use of the sensory trick frames (STF).ResultsA reduction in the score was noted in both severity (p = 0.0115) and frequency patterns (p = 0.0117) in the JRS in patients using the STF. A significant reduction of the BSDI score was also observed (p = 0.0314).ConclusionAll the patients selected and fitted with the STF had a reduction in spasms and related symptoms. This new device may be helpful in some selected BEB patients who previously responded positively to periocular pressure alleviating maneuvers.

Glucose hypometabolism in the visual cortex proportional to disease severity in patients with essential blepharospasm.

Essential blepharospasm (EB) causes difficulty in eyelid opening because of involuntary movements of the orbicularis oculi muscle. Patients with EB have functional visual loss due to sustained eyelid closure. We examined cerebral glucose metabolism in 39 patients with EB (12 men and 27 women; mean age, 52.1 years) by using positron emission tomography with 18F-fluorodeoxyglucose. Forty-eight eye open healthy subjects and 48 eye close healthy subjects served as controls. We analyzed and compared the data between the patients and controls by using both statistical parametric mapping (SPM) and regions of interest (ROIs). We defined ROIs on both sides of the posterior striate cortex, anterior striate cortex, extrastriate cortex, and thalamus. In SPM analysis, glucose hypometabolism were observed in both sides of the extrastriate cortex compared to eye open controls but not to eye close controls. We also observed a significant negative correlation between the Jankovic Rating Scale (JRS) sum score and relative glucose metabolism level in the striate cortex of these patients. ROI analysis, a significant correlation was observed between the JRS sum score and glucose metabolism level in the posterior (right: r = −0.53, P = .0005; left: r = −0.65, P = .00001) and anterior (right: r = −0.33, P = .04; left: r = −0.37, P = .02) striate cortices of patients with EB. We surmise that the interruption of visual input cause glucose hypometabolism in the visual cortex of patients with EB.

Resting state fMRI observations of baseline brain functional activities and connectivities in primary blepharospasm.

Primary blepharospasm (BPS) is a focal dystonia characterized by involuntary eyelid spasms and blinking. The pathophysiology of BPS remains unclear. Several functional and structural neuroimaging studies have demonstrated abnormalities of sensorimotor structures such as the sensorimotor cortex, the basal ganglia, the thalamus and the cerebellum in BPS patients. However, some of the results of these studies were inconsistent. In addition, the relationship between the motor and sensory structures in patients with BPS still needs to be investigated. Therefore, the purpose of this study was to investigate the abnormal alterations in both the intra-regional brain activities and inter-regional functional connectivities (FC) in patients with BPS using resting-state functional MRI(rs-fMRI) and to explore possible correlations between these rs-fMRI indices and clinical variables. The rs-fMRI images of the two groups of subjects (26 BPS patients and 26 healthy controls) were acquired using a 3.0T MRI scanner. The regional rs-fMRI indices, i.e., the fractional amplitude of the low-frequency fluctuation (fALFF) and the regional homogeneity (ReHo), were computed for all subjects. Then, two-sample t-tests were conducted to assess the significant differences between the two groups of subjects. To investigate the alterations in brain networks, cerebral regions with significant differences were used as regions of interest in the whole brain FC analysis. Compared to the control group, the BPS patients revealed significantly increased fALFF and ReHo values in the right caudate head. Significantly strengthened FC values were observed between the right caudate head and the left striatum and the right supplementary motor area in the BPS group. The fALFF and ReHo values in the right caudate head and the FC values between the right caudate head and the left striatum were positively correlated with the Jankovic Rating Scale sum score. In conclusion, this study indicated that BPS patients have both abnormal intra-regional spontaneous brain activities and inter-regional functional connectivities.

右美沙芬治疗特发性眼睑痉挛的回顾性分析

背景：眼睑痉挛是一种局限性肌张力障碍，患者眼睛周围的肌肉频繁不自主收缩导致眼睑闭合和视力障碍。目前治疗眼睑痉挛的效果并不是很理想。本文是一项右美沙芬对眼睑痉挛疗效的回顾性研究。方法：回顾性研究包括22例特发性眼睑痉挛，患者接受右美沙芬治疗，30mg 每天三次口服，采用扬科维奇评分(Jankovic Rating Scale, JRS)和眼睑痉挛的残疾指数(Blepharospasm Disability Index, BSDI)评价疗效。结果：右美沙芬治疗前基线JRS评分是5.55±1.10分，BSDI基线评分为2.87±0.59。右美沙芬治疗1周后，JRS评分下降到2.82 ± 0.85分，BSDI下降到1.36 ± 0.58分。在接下来的3周的治疗，JRS和BSDI得分保持在一个稳定的状态。停止右美沙芬治疗一周后，JRS评分(5.41 ± 1.01分)和BSDI评分(2.63 ± 0.64分)回到治疗前的基线水平。结论：本研究发现右美沙芬对眼睑痉挛患者有效，这一发现可能意味着另一种治疗选项。 Background: Blepharospasm is a focal dystonia characterized by intermittent or continual invo-luntary contractions of the facial muscles around both eyes. It causes frequent eyelid closure and visual disturbance. The current therapies for blepharospasm are not satisfactory. Here is a retrospective study to analyze the therapeutic effect of dextromethorphan on blepharospasm. Methods: This retrospective study included 22 patients with blepharospasm. They were treated with dextromethorphan, 30 mg orally three times a day for 4 weeks. The effect of dextromethorphan on essential blepharospasm was evaluated using Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI). Results: Before treatment, the baseline JRS score was 5.55 ± 1.10 points, and the BSDI score was 2.87 ± 0.59 points. After 1 week of dextromethorphan treatment, the JRS score decreased to 2.82 ± 0.85 points and the BSDI score to 1.36 ± 0.58 points. In the following 3 weeks of dextromethorphan treatment, the JRS and BSDI scores kept in a steady state. One week after the dextromethorphan treatment, the JRS (5.41 ± 1.01 points) and BSDI (2.63 ± 0.64 points) scores returned to the pre-treatment baseline level. Conclusion: We found that dextromethorphan is effective to relieve the symptoms in patients with blepharospasm, and this finding might imply an alternative treatment option to essential blepharospam.

Dextromethorphan is Effective for Essential Blepharospasm

Background: Blepharospasm is a focal dystonia presented with continuous involuntary contractions of the muscles surrounding the eyes, causing frequent eyelid closure and visual disturbance. The current treatments for blepharospasm are not very satisfactory. This is a retrospective study of the therapeutic effect of dextromethorphan on blepharospasm. Methods: This retrospective study included 22 patients with essential blepharospasm, who were treated with dextromethorphan. The effect was evaluated using Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI). Results: Before dextromethorphan treatment, the baseline JRS score is 5.55 ± 1.10 points, and the BSDI score was 2.87 ± 0.59 points. After 1 week of dextromethorphan treatment, the JRS score decreased to 2.82 ± 0.85 points, and the BSDI score decreased to 1.36 ± 0.58 points. In the following 3 weeks of treatment, the JRS and BSDI scores kept in a steady state. One week after the dextromethorphan treatment, the JRS score (5.41 ± 1.01 points) and BSDI score (2.63 ± 0.64 points) returned to the pre-treatment baseline level. Conclusion: We found that dextromethorphan is effective in patients with blepharospasm, and this finding might imply an alternative treatment option to blepharospams.

Objective, computerized video-based rating of blepharospasm severity.

To compare clinical rating scales of blepharospasm severity with involuntary eye closures measured automatically from patient videos with contemporary facial expression software. We evaluated video recordings of a standardized clinical examination from 50 patients with blepharospasm in the Dystonia Coalition's Natural History and Biorepository study. Eye closures were measured on a frame-by-frame basis with software known as the Computer Expression Recognition Toolbox (CERT). The proportion of eye closure time was compared with 3 commonly used clinical rating scales: the Burke-Fahn-Marsden Dystonia Rating Scale, Global Dystonia Rating Scale, and Jankovic Rating Scale. CERT was reliably able to find the face, and its eye closure measure was correlated with all of the clinical severity ratings (Spearman ρ = 0.56, 0.52, and 0.56 for the Burke-Fahn-Marsden Dystonia Rating Scale, Global Dystonia Rating Scale, and Jankovic Rating Scale, respectively, all p < 0.0001). The results demonstrate that CERT has convergent validity with conventional clinical rating scales and can be used with video recordings to measure blepharospasm symptom severity automatically and objectively. Unlike EMG and kinematics, CERT requires only conventional video recordings and can therefore be more easily adopted for use in the clinic.

Use of Alleviating Maneuvers for Periocular Facial Dystonias

Patients with benign essential blepharospasm or hemifacial spasm are known to use botulinum toxin injections and alleviating maneuvers to help control their symptoms. The clinical correlates between the use of botulinum toxin injections and the use of alleviating maneuvers are not well established. To determine whether the use of alleviating maneuvers for benign essential blepharospasm or hemifacial spasm correlates with disease severity or botulinum toxin treatment. A prospective cross-sectional observational study (designed in September 2013) of 74 patients with benign essential blepharospasm and 56 patients with hemifacial spasm who were consecutively recruited from adnexal clinics at Moorfields Eye Hospital (January-June 2014) to complete a questionnaire and undergo a clinical review. Data analysis was performed in December 2015. Prevalence and type of alleviating maneuvers used for blepharospasm and hemifacial spasm, dystonia severity, and dose and frequency of botulinum toxin injections. Of the 74 patients with blepharospasm, 39 (52.7%) used alleviating maneuvers (mean [SD] age, 70.4 [9.1] years); of the 56 patients with hemifacial spasm, 25 (44.6%) used alleviating maneuvers (mean [SD] age, 66.5 [12.7] years). The most commonly used maneuver was the touching of facial areas (35 of 64 patients [54.7%]); other maneuvers included covering the eyes (6 of 64 patients [9.4%]), singing (5 of 64 patients [7.8%]), and yawning (5 of 64 patients [7.8%]). Patients with blepharospasm who used alleviating maneuvers scored higher on the Jankovic Rating Scale (median score, 5 vs 4; Hodges-Lehmann median difference, 1 [95% CI, 0-2]; P = .01) and the Blepharospasm Disability Index severity score (median score, 11 vs 4; Hodges-Lehmann median difference, 4 [95% CI, 1-7]; P = .01) than patients with blepharospasm who did not use alleviating maneuvers. Patients with hemifacial spasm who used alleviating maneuvers scored higher on the 7-item Hemifacial Spasm Quality of Life scale (median score, 7 vs 3; Hodges-Lehmann median difference, 4 [95% CI, 1-7]; P = .01) and the SMC Severity Grading Scale (median score, 2 vs 2; Hodges-Lehmann median difference, 0 [95% CI, 0-1]; P = .03) than patients with hemifacial spasm who did not use alleviating maneuver. The severity of dystonia correlated with botulinum toxin treatment for patients with blepharospasm (r = 0.23; P = .049) and patients with hemifacial spasm (r = 0.45; P = .001). There was no difference found in botulinum toxin treatment between patients who used alleviating maneuvers and those who did not, in either the blepharospasm group (150 vs 125 units; Hodges-Lehmann median difference, 20 units [95% CI, -10 to 70 units]; P = .15) or the hemifacial spasm group (58 vs 60 units; Hodges-Lehmann median difference, 0 units [95% CI, -15 to 20 units]; P = .83). Half of the patients with periocular facial dystonias used alleviating maneuvers. Their use was associated with more severe disease but not with increased use of botulinum toxin. This may help to guide future therapies, such as advice on maneuver augmentation or tailored devices.

A cross-sectional structured survey of patients receiving botulinum toxin type A treatment for blepharospasm

To characterize satisfaction with current standard-of-care botulinum neurotoxin type A (BoNT/A) treatment for blepharospasm, we performed a cross-sectional, structured survey in subjects with blepharospasm who had received ≥2 BoNT/A cycles. Subjects were interviewed immediately before re-injection to evaluate treatment satisfaction, time course of treatment effects, preferred injection intervals, Jankovic Rating Scale (JRS), and Blepharospasm Disability Index (BSDI).Subjects’ (n=114) last treatment was onabotulinumtoxinA (n=78), incobotulinumtoxinA (n=35), or abobotulinumtoxinA (n=1). The most frequent injection interval was 12weeks (46.5% subjects); 30.7% had an interval >12weeks. The main rationale for interval choice was “to maintain treatment efficacy” (44.7%). However, 36.6% reported that treatment effects usually declined within 8weeks; 69.6% within 10weeks. JRS and BSDI scores indicated re-emergence of symptoms before re-injection, with 70.2% and 73.7% of subjects reporting difficulties to drive and read, respectively. Overall, treatment satisfaction was high, but declined at the end of the cycle. Many subjects (52.3%) would prefer an injection interval of <12weeks; 30.6% of <10weeks.In conclusion, the survey results indicate that blepharospasm symptoms, such as difficulties to drive and read, re-emerge at the end of a BoNT treatment cycle and that flexible, individualized treatment intervals may improve treatment satisfaction and outcomes.

Comparison of Two Botulinum Neurotoxin A Injection Patterns with or without the Medial Lower Eyelid in the Treatment of Blepharospasm.

The aim of this study was to evaluate the efficacy of two botulinum toxin A (BoNT-A) injection patterns with or without the medial lower eyelid (MLE) in treating benign essential blepharospasm (BEB) and influencing lacrimal drainage. Two different injection patterns of BoNT-A were randomly applied to 98 eyes of 49 BEB patients: MLE Group received a full injection pattern of 5 sites and non-MLE Group received a MLE waived injection pattern of 4 sites. Tear breakup time (BUT), Schirmer I test, lagophthalmos height, and lower lid tear meniscus height (TMH) were measured and Jankovic Rating Scale (JRS) was surveyed before injection and at 1 week, 1 month, and 3 months after injection. The symptom of BEB was relieved in both groups as suggested by JRS scores at all time points after injection, and MLE Group came up with a better JRS score at 3 months. The increases of Schirmer I test value and TMH in MLE Group were higher than those in non-MLE Group at 1 week after injection. This study shows that the MLE-involved full injection pattern is a better choice for patients with BEB. It has longer-lasting effects in relieving BEB symptoms and better efficacy in reducing lacrimal drainage. Clinical Trials registration number is NCT02327728.

Observational Study of IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm (XCiDaBLE): Interim Results for the First 170 Subjects with Blepharospasm.

BackgroundXCiDaBLE is a large, prospective, observational “naturalistic” study evaluating Xeomin® for Cervical Dystonia or BLEpharospasm in the United States. We report the interim results from the blepharospasm cohort of XCiDaBLE.MethodsSubjects (≥18 years old) with blepharospasm were followed for two treatment cycles of incobotulinumtoxinA and monitored for 4 weeks after injection via interactive voice/web response system (IVRS/IWRS). The investigator-reported scale includes the Clinical Global Impression Scale-Severity subscale (CGI-S). Patient-reported outcome measures include the Patient Global Impression Scale-Severity (PGI-S) and -Improvement (PGI-I) subscales, Jankovic Rating Scale (JRS), SF-12v2® health survey, and Work Productivity and Activity Impairment questionnaire. Subjects are seen by the investigator at baseline (including the first injection), during the second injection, and at a final study visit (12 weeks after the second injection).ResultsOne hundred seventy subjects were included in this interim analysis. The majority of subjects were female (77.1%) and white (91.8%), and had previously been treated with botulinum toxins (96.5%). The mean total dose (both eyes) was 71.5 U of incobotulinumtoxinA for the first injection. PGI-S, PGI-I, and JRS scores were significantly improved 4 weeks after treatment (all p<0.0001). No differences were noted in either quality of life (QoL) or work productivity in this short assessment period. No unexpected adverse events occurred.DiscussionThis is an interim study and assessment method based on an IVRS/IWRS. In this predominantly toxin-experienced cohort, significant benefits in specific and global measures of disease severity were seen in the immediate post-incobotulinumtoxinA injection period. It will be interesting to see if there are improvements in QoL with consistent individualized injections over a longer period.

Altered regional spontaneous neuronal activity in blepharospasm: a resting state fMRI study

The resting state amplitude of low-frequency fluctuations (ALFF) in functional magnetic resonance imaging (fMRI) is believed to reflect spontaneous cerebral neural activity. The pathophysiology of blepharospasm (BSP), which is characterized by motor symptoms and also sensory symptoms, remains unclear. The present study aims to localize possible cerebral functional abnormalities in BSP patients using resting state fMRI, and explore their possible associations with clinical variables. Voxel-based analysis was used to characterize the difference of ALFF between eighteen BSP patients and eighteen matched healthy controls. Separate correlation analyses were conducted to explore the possible association between ALFF values of significantly different areas and clinical measures including onset age, disease duration, symptom severity evaluated by Jankovic rating scale (JRS), and presence of geste antagoniste. The whole-brain analysis indicated that the BSP group had significantly decreased ALFF in the left thalamus while increased ALFF in the left orbitofrontal areas extending from middle frontal gyrus to inferior frontal gyrus. The mean ALFF in the left thalamus was negatively correlated with the subscore of JRS-frequency (r=-0.484, p=0.042) and JRS total score (r=-0.477, p=0.045). A borderline positive correlation was detected between the mean ALFF in the left orbitofrontal area and disease duration(r=0.485, p=0.049). Our findings suggest sensorimotor integration is abnormal in BSP, and dysfunctional activity of thalamus may be used to measuring symptom severity in BSP patients.