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Kilduff CLS, Casswell EJ, Salam T, Hersh D, Ortiz-Perez S, Ezra D. Use of Alleviating Maneuvers for Periocular Facial Dystonias. JAMA Ophthalmol. 2016;134(11):1247–1252. doi:10.1001/jamaophthalmol.2016.3277
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Is the use of alleviating maneuvers by patients with benign essential blepharospasm (BEB) or hemifacial spasm (HFS) associated with disease severity or botulinum toxin treatment?
The use of alleviating maneuvers was associated with more severe disease in both patients with BEB and patients with HFS, but not with increased use of botulinum toxin.
Although this association is not proof of cause and effect, patients with BEB or HFS with severe disease may benefit from a multimodal approach to their care, including advice on augmenting their maneuvers or tailoring devices to mimic their maneuvers.
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.
Design, Setting, and Participants
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.
Main Outcomes and Measures
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).
Conclusions and Relevance
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.
Benign essential blepharospasm (BEB) typically presents in the fifth and sixth decades of life.1 Symptoms can be severe, rendering some patients functionally blind.2 The etiology of BEB is not fully understood, although magnetic resonance imaging studies indicate involvement of the basal ganglia, thalamus, and cerebellum.3,4 Abnormalities in the afferent arm of the blink reflex have also been implicated.5 Hemifacial spasm (HFS) usually appears in the fourth to sixth decade of life. It is generally accepted that HFS is caused by vascular impingement of the facial nerve near its origin from the brainstem.1
Medical therapy for BEB and HFS includes management of concurrent dry eye disease and pharmacological treatment.6 A meaningful response to medical therapy for HFS is reported in less than 10% of patients.7 Anticholinergics, antiepileptics, and presynaptic monoamine-depleting agents can offer limited symptomatic relief for some patients with BEB, but the adverse effects are often dose-limiting, particularly in elderly patients.8 Surgery is reserved for those who do not respond to medical therapy or botulinum toxin (BTX) injections. Surgical options for BEB and HFS include facial nerve fiber disruption, percutaneous thermolysis, and myectomy procedures.9 These rarely offer long-term symptomatic relief and carry the risk of permanent postoperative complications.10
Periocular BTX injections currently form the most common treatment modality for both patients with BEB and patients with HFS. Botulinum toxin inhibits the release of acetylcholine at the neuromuscular junction by preventing the fusion of neurotransmitter axonal vesicles, causing flaccid paralysis. Treatment with BTX has a transient effect and offers 90% of patients clinically significant symptomatic relief for 8 to 16 weeks. However, the response to BTX can vary widely, with some patients perceiving no benefit.11
Quiz Ref IDA distinct phenomenon in dystonia is the sensory trick or geste antagoniste. Sensory tricks are purposeful maneuvers that temporarily reduce the severity of dystonic posturing and/or movements.12,13 Previous studies suggest that 55% to 72% of patients with BEB and 38.5% of patients with HFS use trick maneuvers to alleviate their symptoms.14,15 Many different maneuvers have been described as sensory tricks; the most common is touching specific areas of the face (mostly the upper eyelid), but humming, whistling, yawning, coughing, adjusting glasses, and covering 1 eye, among others, have also been reported.13 Because these maneuvers can involve not only sensory but also motor stimulation,16 they have recently been referred to more accurately as alleviating maneuvers.17 The mechanism underlying this phenomenon is unclear, but alleviating maneuvers seem to reduce cortical activity in the supplementary motor cortex, perhaps by altering central processing.18
We aimed to assess the prevalence of the alleviating maneuvers used among patients with BEB or HFS and whether the use of these maneuvers is related to both disease severity and treatment with BTX injections. One might expect that as disease severity increases, the patient would develop alleviating maneuvers for disease control. As such, it may act as a proxy for disease severity. If alleviating maneuvers are associated with more severe disease, this may help to guide future therapies and tailor patient management. To our knowledge, this is the first study to investigate the relationship between BEB or HFS severity and the use of alleviating maneuvers.
Ethical approval from Moorfields Eye Hospital was sought and obtained before commencing the study (September 2013). All patients provided written informed consent. The study recruited 130 consecutive patients from the facial dystonia clinic at Moorfields Eye Hospital (January-June 2014). Patients with an established diagnosis of BEB or HFS who were in the stable phase of their treatment and receiving BTX therapy on a regular basis were included. Stable treatment was defined clinically as patients whose BTX therapy had been deemed to be optimized and were receiving stable repeated doses for 3 or more cycles of treatment. The dosing of BTX was determined clinically based on many factors, including discussion with the patient, previous adverse effects, and expectations of the patient. The clinical team involved in making these decisions was the same for both patient groups. Patients with secondary blepharospasm due to ocular surface disease were excluded.
All patients completed a questionnaire to measure disease severity using validated disability rating scales. The patients with BEB completed the Jankovic Rating Scale and the Blepharospasm Disability Index (BSDI). The patients with HFS competed the 7-item Hemifacial Spasm Quality of Life (HFS-7 QOL) Questionnaire and the SMC Severity Grading Scale.19 Both the patients with BEB and the patients with HFS ranked the severity of spasms when BTX treatment was at its maximum effect and the consequent effect of spasms on daily activities. All patients then answered a questionnaire regarding the use of alleviating maneuvers and their resultant benefits.
The clinician objectively measured corneal sensation using a Cochet-Bonnet Corneal Aesthesiometer and assessed the ocular surface using the Oxford Scheme.20 The dose of BTX, the type of BTX, and the frequency of BTX injections were also recorded.
The vast majority of patients received Dysport (Medicis Pharmaceutical Corp); however, 3 patients received NeuroBloc (Solstice Neurosciences), and 5 patients received Botox (Allergan). For dose comparison, relative to Dysport, NeuroBloc was corrected at a 50:1 dose ratio, and Botox at a 0.33:1 dose ratio.21
The Mann-Whitney test was used to compare severity scores, corneal aesthesiometry and ocular surface scores, and BTX doses. An unpaired t test was used to compare the ages of patients and injection frequencies. Correlation analyses were based on the Spearman rank correlation test. Median values (interquartile ranges) are reported for nonparametric variables; mean values (SD) are reported for age and BTX frequency. The Hodges-Lehmann median difference and 95% CIs are reported for nonparametric data. Statistical analysis was performed using GraphPad Prism software, version 6 (GraphPad Software Inc). Statistical significance was set at P < .05.
Quiz Ref IDTable 1 shows the demographic and clinical characteristics of patients with BEB who did or did not use alleviating maneuvers. Of the 74 patients with BEB, 39 (52.7%) used alleviating maneuvers, and 35 (47.3%) did not. The patients 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 BSDI severity score (median score, 11 vs 4; Hodges-Lehmann median difference, 4 [95% CI, 1-7]; P = .01) than the patients who did not. There was no difference between the 2 groups with regard to corneal aesthesiometry, corneal stain, BTX dose, or BTX injection frequency.
The Spearman rank correlation test revealed a strong correlation between the use of alleviating maneuvers and both the Jankovic Rating Scale score (r = 0.71; P < .001) and the BSDI total score (r = 0.29; P = .01). There was no correlation between use of alleviating maneuvers and BTX dose or injection frequency.
The Jankovic Rating Scale score correlated with the BSDI total score (r = 0.58; P < .001), BTX dose (r = 0.23; P = .049), and BTX injection frequency (r = −0.26; P = .03). The BSDI total score correlated with BTX injection frequency (r = −0.31; P = .01). No other correlation was found between any of the other variables, aside from corneal aesthesiometry being negatively correlated with age (r = −0.27; P = .03).
Quiz Ref IDTable 2 shows the demographic and clinical characteristics of patients with HFS patients who did or did not use alleviating maneuvers. Of the 56 patients with HFS, 25 (44.6%) used alleviating maneuvers, and 31 (55.4%) did not. The patients who used alleviating maneuvers scored higher on the HFS-7 QOL 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 the patient who did not. There was no difference between the 2 groups with regard to corneal aesthesiometry, corneal stain, BTX dose, or BTX injection frequency.
The Spearman rank correlation test revealed a correlation between the use of alleviating maneuvers and both the HFS-7 QOL scale score (r = 0.37; P = .004) and the SMC Severity Grading Scale score (r = 0.31; P = .02). There was no correlation between use of alleviating maneuvers and BTX dose or injection frequency. The SMC Severity Grading Scale score correlated with the HFS-7 QOL scale score (r = 0.35; P = .009), age (r = −0.36; P = .02), and BTX dose (r = 0.45; P = .001). No other correlation was found between any of the other variables.
Quiz Ref IDTable 3 shows the perceived benefits of the use of alleviating maneuvers to reduce the symptoms of facial dystonia. Overall, 35 of 61 patients (57.4%) found that their alleviating maneuvers reduced the symptoms of dystonia by at least 50% (24 of 37 patients with BEB [64.9%] and 11 of 24 patients with HFS [45.8%]). Table 4 shows the types of alleviating maneuvers used by patients with BEB or HFS. The most commonly used alleviating maneuver was the touching of specific 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%]).
To our knowledge, this study is the largest observational study of the use of alleviating maneuvers for patients with BEB or HFS to date, and it is the first to investigate the relationship between these maneuvers and both disease severity and BTX treatment.
Our study found that 39 of 74 patients with BEB (52.7%) and 25 of 56 patients with HFS (44.6%) used alleviating maneuvers. Of the patients that use alleviating maneuvers, 64.9% of the patients with BEB and45.8% of the patients with HFS reported that their maneuver either abolished or reduced the symptoms of dystonia by at least 50%. Martino et al15 found that 42 of 59 patients with BEB (71.2%) used alleviating maneuvers, and Loyola et al14 reported that 55% of patients with BEB and 38.5% of patients with HFS used alleviating maneuvers. For these patients, the maneuvers abolished or reduced the symptoms of dystonia by at least 50% in 63.6% of patients with BEB and 50% of patients with HFS. This is in keeping with our findings and further strengthens the observation that patients with HFS benefit from alleviating maneuvers, which had only previously been reported by Loyola et al.14
This study reports novel findings that the use of alleviating maneuvers correlated strongly with disease severity, in both patients with BEB and patients with HFS. Although the underlying mechanism for this phenomenon is not clear, it may support the input-output mismatch hypothesis for the development of dystonia.22 There is a growing body of evidence that proprioceptive dysfunction and abnormal sensorimotor integration exist in focal dystonias, with loss of mechanisms such as cortical surround inhibition.23 Proprioceptive dysfunction in BEB is supported by a recent study5 that found a reduction in both corneal sensitivity and the number of subbasal corneal nerves in patients with BEB. Dystonia and BEB may therefore result from a mismatch between sensory input and motor output, with a resultant increase in the facilitation to inhibition ratio.16 Indeed, alleviating maneuvers have previously been shown to reduce this abnormal increase in intracortical facilitation.24 Therefore, it is possible that as disease severity increases, with an increase in the facilitation to inhibition ratio, patients develop alleviating maneuvers as a corrective inhibitory afferent input. As such, alleviating maneuvers may be a proxy for worsening disease. A previous study by Patel et al17 that looked at cervical dystonia found no correlation between disease severity and the use of alleviating maneuvers. However, their study17 had a large discrepancy in group size (154 people who used alleviating maneuvers vs 16 people who did not), and, as the authors acknowledge, this may well have hidden any potential correlation.
We found no difference in BTX treatment between patients who use alleviating maneuvers and those who do not, in both the BEB and HFS groups. This is perhaps surprising given that we found that overall disease severity correlated with increased use of BTX. Interestingly, a recent study25 found that patients with cervical dystonia who use alleviating maneuvers derive more subjective benefit from BTX treatment than patients with cervical dystonia who do not use alleviating maneuvers. This is supported by a functional magnetic resonance imaging study,26 which found that the administration of BTX led to reduced activity in the supplementary motor area, an area that also shows reduced activation during the performance of alleviating maneuvers.18 Therefore, alleviating maneuvers may act as a substitute for BTX treatment. This may explain why our patients who used alleviating maneuvers did not require higher BTX doses, despite having more severe symptoms of the disease.
The majority of both the patients with BEB and the patients with HFS touched specific areas of their face to alleviate their dystonia, in keeping with previous series.14,15 Other alleviating maneuvers included motor activity, such as singing, yawning, and opening or closing the eyes, as well as sensory stimulation, such as covering the eyes. These have previously been described, but their frequency of use has not previously been reported. Classically, sensory tricks have described maneuvers that involve predominantly sensory stimulation, but our findings, and those of others,16,27 support the notion that motor stimulation is an important part of alleviating maneuvers. Therefore, strictly sensory tricks form a subset of the alleviating maneuvers used to reduce the symptoms of dystonia.
The physiology underlying both sensory and nonsensory alleviating maneuvers used by patients with dystonia is not fully understood and seemingly complex. Studies investigating the “sensory trick” phenomenon using electromyography and neuroimaging suggest that proprioceptive or sensory stimulation can influence sensorimotor integration, with a resultant reduction in abnormal motor output.18,28 Indeed, the nonsensory or motor component of sensory tricks also seems to be of particular importance. One study29 found that one-third of patients experience a trick’s benefit prior to contact with their sensory target and that the majority of patients seemed to get no benefit if another individual performs the sensory trick on their behalf.28 Indeed, one study25 even found that 15% of patients benefited from purely imagining performing their sensory trick. This suggests that the initiation of movement is also important in influencing sensorimotor integration and helps explain why maneuvers such as singing and yawning were effective in reducing the symptoms of dystonia. The observation that intricate, combined motor/sensory activities such as dancing and playing the piano30 are also effective certainly suggests that the mechanism underlying alleviating maneuvers is indeed complex. It is interesting that an action such as covering the eyes was noted to reduce the symptoms of BEB. This is in keeping with a recent randomized case-control study that found a reduction in BEB severity if patients wore FL-41–tinted spectacles.31 A positron emission tomographic study18 found activation of the visual cortices during alleviating maneuvers, even when the participants’ eyes were closed. This prompted the authors to suggest that this cortical area is part of the complex neuronal network activated by alleviating maneuvers.18 It is possible that by covering their eyes, the patients are able to augment this network, thus reducing their symptoms of dystonia.
It is less clear why patients with HFS, which is classed as a myoclonic rather than a dystonic condition, benefit from alleviating maneuvers. This is an observation that has only recently been reported.14 It is generally thought that HFS is caused by vascular impingement at the root of the facial nerve by the posterior circulation. Evidence, however, suggests that increased excitability of the facial nucleus may also contribute to the pathophysiology.32 It is therefore conceivable that sensory/motor stimulation may also centrally inhibit motor activity from the facial nucleus, in a similar way to what has been proposed for BEB. Further studies are needed to investigate these potential mechanisms.
This study shows that despite treatment with BTX, patients still experience symptoms of severe disease. Treatment with BTX is also not without its risks. Patients and clinicians have to strike the balance between symptom control and the adverse effects of the treatment. We found an association in this study between those patients who report more severe symptoms and the use of alleviating maneuvers. Furthermore, both the patients with BEB and the patients with HFS reported a benefit from their alleviating maneuvers, and half reported a more than 50% decrease in the movement after using their maneuver. These patients may therefore be good candidates for a multimodal approach to their care, including advice on augmenting their alleviating maneuvers or tailoring devices to mimic the maneuver to help maximize the effect. Pressure devices, in particular, may potentially be useful in mimicking the effect of touching specific parts of the face to stop the spasms.
There were several limitations to this study. Patients were recruited from a specialist clinic at a single center. So we may have selected patients with a more severe disease profile, although the average age of the patients and the prevalence of the alleviating maneuvers used were similar to a previous study.14 Patients reported their alleviating maneuvers via a questionnaire, rather than through direct observation. This may have led to a degree of recall bias. Not all parameters in the severity scales were relevant to all the patients (eg, driving). This may have affected the results, although the number of patients affected was similar in both groups.
In conclusion, approximately half of all patients with periocular facial dystonia use alleviating maneuvers. The use of alleviating maneuvers was associated with greater disease severity but not with increased use of BTX.
Accepted for Publication: July 18, 2016.
Corresponding Author: Edward J. Casswell, MBBS, Adnexal Department, Moorfields Eye Hospital, 162 City Rd, London EC1V 2PD, England (firstname.lastname@example.org).
Published Online: September 8, 2016. doi:10.1001/jamaophthalmol.2016.3277
Author Contributions: Dr Casswell had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Kilduff and Casswell are considered joint first authors.
Study concept and design: Salam, Hersh, Ortiz-Perez, Ezra.
Acquisition, analysis, or interpretation of data: Kilduff, Casswell, Salam, Hersh, Ortiz-Perez.
Drafting of the manuscript: Kilduff, Casswell, Salam, Ezra.
Critical revision of the manuscript for important intellectual content: Casswell, Salam, Hersh, Ortiz-Perez, Ezra.
Statistical analysis: Kilduff, Casswell, Salam, Ezra.
Obtained funding: Ezra.
Administrative, technical, or material support: Salam, Ezra.
Study supervision: Salam, Hersh, Ortiz-Perez, Ezra.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Funding/Support: Dr Ezra acknowledges support from the Department of Health through the award made by the National Institute for Health Research to the Moorfields Eye Hospital NHS Foundation Trust and the University College London Institute of Ophthalmology for a Specialist Biomedical Research Centre for ophthalmology.
Role of the Funder/Sponsor: The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.
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