Original Paper Received: December 12, 2014 Accepted: March 15, 2015 Published online: May 19, 2015
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases in China Xiao-Feng Huang a Kai-Yue Wang b Zhan-Hua Liang a Rong-Rong Du c Li-Na Zhou a
a
Department of Neurology, First Affiliated Hospital of Dalian Medical University, Dalian, b Department of Neurology, Linyi City People’s Hospital, Linyi and c Department of Neurology, First Affiliated Hospital of Baotou Medical College, Baotou, China
Abstract Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. Results: The age of onset was 56.4 ± 2.7 (range, 32– 76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2–120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. Conclusions: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0014–3022/15/0736–0337$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
Primary blepharospasm (PBS) is a focal dystonia that often begins insidiously and progressively worsens. Blepharospasm is characterized by excessive involuntary narrowing or closing of the eyelids; it frequently results in eyelid closure and visual disability [1]. It usually appears in adults and more frequently affects female. Severe blepharospasm has a disabling effect on work and everyday activities and may cause social embarrassment and catastrophic traffic accidents [2–4]. Patients with blepharospasm often first consult an ophthalmologist. Until recently, only a few reports had been published on the demographic and clinical features of blepharospasm [4–6]. This study explored the demographic and clinical features of blepharospasm in China. The findings of this study should increase the awareness of blepharospasm and improve physicians’ understanding of differential diagnoses. Patients and Methods This retrospective study was conducted at the Botulinum Toxin Injection Special Clinic and Movement Disorders Special Clinic in the First Affiliated Hospital of Dalian Medical University.
Zhan-Hua Liang Department of Neurology First Affiliated Hospital of Dalian Medical University 222 Zhong-shan Road, Dalian 116011, Liaoning Province (China) E-Mail zhanhualiang @ 163.com
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
Key Words Focal dystonia · Blepharospasm · Dry eyes · Photophobia · Myasthenia gravis · Botulinum toxin
Results
Seventy-two female (72%) and 28 male (28%) patients participated in this study. The female:male ratio was 2.6:1. The mean age of onset was 56.4 ± 2.7 (range, 32–76 years). The mean duration between the time of onset to the time of accurate diagnosis was 38.7 ± 36.0 months (range, 2–120 months). The age of blepharospasm onset was prior or at 40 in 12% of patients, between the ages of 41 and 50 in 14%, between the ages of 51 and 60 in 44%, between the ages of 61 and 70 in 24%, and older than 70 years old in 6%. Seventy-three patients (73%) had emotional incentives, including depression and anxiety. Twenty-three percent of the patients had merged oromandibular dystonia (OMD), one patient had merged cervical dystonia (CD), two patients had merged Parkinson’s disease, and one patient had an accompanied tic. Five patients (5%) had a family history of movement disorders such as Parkinson’s disease and essential tremor (table 1). The most frequent complaints were dry eyes, difficulty in opening the eye, increased blinking, and photophobia (table 2). The time intervals between initial symptoms to obvious orbicularis oculi muscle spasms were as follows (median time): eyelid twitching, 18 months (range, 1–36 months); dry mouth, 18 months (1–36 months); increased blinking, 12 months (range, 1–60 months); difficulty in opening the eyes, 12 months (range, 1–60 months); dry eyes, 11 months (range, 0.5–24 months); and photophobia, 6 months (range, 1–12 months). Most patients simultaneously or successively developed several symptoms. Twenty-seven percent of the patients had both photophobia and difficulty in eye opening, and 20% had both eye fatigue and dry eyes. Seventy-five percent of patients chose to first consult an ophthalmologist. Only 10% of the patients were correctly diagnosed at the first counseling. Eighteen patients had progressed to functional blindness before an accurate diagnosis was made. The most frequent initial diagnoses were dry eye syndrome, conjunctivitis/keratitis, and myasthenia gravis (MG) (table 3). Of those who first saw an ophthalmologist, 34 patients were initially diagnosed with dry eye syndrome, and 27 were initially diag338
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
Table 1. The demographic and clinical characteristics of blepharospasm patients
Male:female Age at onset, years Symptom duration before accurate diagnosis, months Sensory tricks Emotional disorders Simple PBS PBS + OMD PBS + PD PBS + CD PBS + Tic Family history
28:72 (1:2.6) 56.4±2.7 (32–76) 38.7±36.0 (2–120) 86 73 73 23 2 1 1 5
Table 2. The early symptoms of blepharospasm patients (100 pa-
tients) Early symptoms
No. of patients*
The median time to develop spasm, months
Dry eyes Difficulty of eye opening Increased blinking Photophobia Eyelid twitching Dry mouth Eye pain Facial discomfort Cervical tight Nasal discomfort
54 39 32 32 15 13 9 5 5 4
11 12 12 6 18 18 6 10 7 1
* Many patients simultaneously or successively developed more than one symptom.
Table 3. Number of patients originally misdiagnosed with other
diseases Misdiagnosed diseases
No. of patients (%)
Dry eye syndrome Conjunctivitis/keratitis Myasthenia gravis Neurosis Ametropia Rhinitis Sjogren syndrome
34 (34) 27 (27) 14 (14) 9 (9) 5 (5) 2 (2) 1 (1)
nosed with conjunctivitis/keratitis. Of the patients who first saw a neurologist, 8 were diagnosed with blepharospasm, 7 with myasthenia gravis, and 9 with neurosis. Myasthenia gravis was the secondary tentative diagnosis for 7 cases of patient. In summary, 14 patients of the 100 Huang/Wang/Liang/Du/Zhou
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
From March 2010 to December 2013, 100 patients with blepharospasm were enrolled in this study. Data were collected from medical records and face-to-face interviews with the patients and their families. This study was approved by the Institutional Review Board of the First Affiliated Hospital of Dalian Medical University.
This study retrospectively analyzed 100 patients with primary blepharospasm in China. The results supported previous findings in blepharospasm patients with an average age at the time of onset being in the range of 50 to 60 [3, 6, 7]. The female:male ratio was 2.6:1. This ratio was similar in two previous reports [3, 8] but was higher than that reported by Grandas (1.8:1) [6]. In this study, most of the patients did not receive the correct diagnosis in a timely manner, and the mean duration between onset and accurate diagnosis was more than 3 years. Recently, a study from Italy showed that even in recent years, reaching the correct diagnosis took >1 year in nearly half of patients [8]. Twenty-three percent of the patients had merged OMD, which was a lower rate than that reported by Peckham of 32% [8]. According to previous studies, 7–32% of adult-onset probands had at least one firstdegree relative with dystonia [6, 8, 9]. However, we found that none of the patients with blepharospasm had a family history of any type of dystonia, and only 5% patients had a family history of other movement disorders. Our results suggested that genetic background was not a significant factor in the pathogenesis of adult-onset PBS in the Chinese population. We found that the most frequent symptoms were dry eyes, difficulty in eye opening, increased blinking and photophobia. Dry eye syndrome was a common ophthal-
mological diagnosis for blepharospasm patients. Previous studies showed that dry eyes presented in 40–60% of PBS patients; these findings were consistent with the results of this study [5, 6]. Recently, a study from Asia reported that dry eyes only occurred in 18.9% of patients with PBS [3]. One study [10] followed up 324 cases of new-onset patients with dry eyes; 28 (57%) of the treatment-unresponsive patients were diagnosed with Meige syndrome. Rong’s [11] studies reported that blepharospasm increased dry eyes and other eye inflammation, but focal botulinum toxin injection could relieve these symptoms. Thirty-two of the patients had photophobia, a condition in which bright light from various sources induced irritating ocular discomfort and increased spasms and made it more difficult for the patients to open their eyes; wearing tinted glasses or a hat has a positive effect on these symptoms. Bright light prevented patients from going outdoors alone during the day and at night. Patients noticed that using tinted glasses or a windshield helped relieve their symptoms. This finding was similar with that of another study from Asia [3]. However, Peckham et al. [8] investigated 240 PBS patients (93% Caucasian) and found that only 25% of the patients had photophobia. The inconsistent results may be due to different races of the study population. Moreover, Wen-Juh Hwang reported that only 11% of the patients spontaneously complained of photophobia, but upon questioning, 97% of the patients had photophobia [3]. Eye symptoms associated with PBS result from eye diseases and may be involved in the pathogenesis of PBS [12]. The first-degree relatives of blepharospasm patients more frequently had eye symptoms such as dry eyes and gravel and burning sensations [13]. This study showed that 86% of patients with primary blepharospasm experienced sensory tricks. This figure was similar to the results reported by Peckham et al. [8] and Martino et al. [14], who reported sensory tricks in 87 and 71.2% of patients, respectively. Another study from Brazil reported sensory tricks in only 55% of PBS patients [15]. The tricks used by our patients were similar to those described in the literature [14, 15], including wearing sunglasses, pressing on the forehead or jaw, touching their eyelids, chewing and talking. Although rarely reported, myasthenia gravis is a common diagnosis made by neurologists in patients with blepharospasm [3]. In this study, 14 of the patients with blepharospasm were diagnosed with MG. The difficulty in eye opening is similar to ptosis. The common features for both myasthenia gravis and blepharospasm include predominant eyelid involvement, sleep benefits,
Clinical Analysis of Patients with Primary Blepharospasm in China
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
Discussion
339
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
patients (14%) were originally suspected to have myasthenia gravis. Patients diagnosed with dry eye syndrome accepted regular ophthalmic treatments such as eye drops, which had no effect or had a mild effect. All of the patients who were diagnosed with myasthenia gravis had received a single test or a combination of tests related to myasthenia gravis. Four patients showed a false positive result in a neostigmine test. One patient underwent thymectomy surgery. Patients who were diagnosed with neurosis received anti-anxiety drugs, anti-depression drugs or repetitive transcranial magnetic stimulation therapy. Seven patients who reported both mental and spasm symptoms experienced mild-to-moderate beneficial effects lasting no longer than 3 months. These patients received botulinum toxin type A injections (50–100 IU) in our movement disorder clinic. The duration of the effect of botulinum toxin type A was longer than 3 months in 93 (93%) patients. The mean interval between injections was 5.2 ± 1.6 months (range, 3–10 months).
diurnal changes, relief by rest or local cold water packing, excessive blinking, and photophobia. Although the positive rate of repetitive nerve stimulation (RNS) is up to 80% in general MG, the rate is only 17.2% in simple ocular MG. There are very few patients with comorbid myasthenia gravis and blepharospasm [15, 16]. Considering that botulinum toxin can aggravate muscle weakness in MG, myasthenia gravis should be optimally treated before considering using botulinum toxin in patients with coexisting myasthenia gravis and blepharospasm. Fabbrini et al. [17] reported that 19/28 patients (67.9%) with PBS had anxiety and/or depressive symptoms. After that, a case-control study from the United States reported a higher rate (82%) of anxiety and/or depressive disorders in patients with PBS [18]. The most common psychiatric feature in patients with BPS is depressive disorder [17]. In this study, 73% of the patients experienced negative emotions such as high pressure at work pressure, life stress and death of relatives before disease onset. Most patients had mild to severe anxiety or depression in the early stage, and oral anti-anxiety or anti-depressant medications can relieve both psychiatric symptoms and spasms. In some patients, psychiatric symptoms occurred before or increased with the progression of blepharospasm. In this study, patients diagnosed with psychiatric disorders received oral anti-anxiety and/or anti-depression medications. The spasms and psychiatric symptoms were mildly to moderately improved, but effects were not long lasting. Based on our experience, patients with combined blepharospasm and depression or anxiety experienced a shorter duration of efficacy of botulinum toxin. For such patients, oral medications were helpful in prolonging the efficacy of botulinum toxin. Psychiatric disorders may share a common pathophysiology with dystonia or may arise as a reaction to dystonia [4, 17, 18]. This study has the following significance: (1) the clinical manifestations of blepharospasm vary, and the rate of
accurate diagnosis is very low. Some patients progress to functional blindness, are unable to live and work independently, and even develop suicidal ideations; (2) the ability to differentiate blepharospasm from dry eye syndrome by ophthalmologists must be improved; (3) in some cases, ocular MG and PBS are difficult to identify, and it is thus recommended that MG is considered first and closely followed up; (4) anxiety and depression symptoms may be the early symptoms of blepharospasm and should be closely observed, and (5) local botulinum toxin type A injections are safe and effective to treat blepharospasm. In summary, the early clinical manifestations of blepharospasm include dry eyes (54%), difficulty of eye opening (39%), increased blinking (32%) and photophobia (32%). The majority of patients consulted an ophthalmologist at first. The most frequently diagnosed diseases were dry eye syndrome, conjunctivitis/keratitis, MG and neurosis. Our study showed that it is necessary for ophthalmologists and neurologists to improve their understanding of blepharospasm, which will be of great benefit for accurately diagnosing and treating patients in a timely manner and for preventing the progression to functional blindness.
Acknowledgment This study was supported by Liaoning Province Natural Science Foundation-funded Project (No. 201102052).
Disclosure Statement We declare that we have no financial and personal relationships with other people or organizations that could inappropriately influence our work. There are no professional or other personal interests of any nature or type in any product, service and/or company that could be construed as having influenced the conclusions presented in or the review of this manuscript.
1 Hallett M, Evinger C, Jankovic J, Stacy M: Update on blepharospasm: report from the BEBRF international workshop. Neurology 2008;71:1275–1282. 2 Hwang WJ, Tsai CF: Motor vehicle accidents and injuries in patients with idiopathic blepharospasm. J Neurol Sci 2014;339:217–219. 3 Hwang WJ: Demographic and clinical features of patients with blepharospasm in
340
southern Taiwan: a university hospital-based study. Acta Neurol Taiwan 2012;21:108–114. 4 Biuk D, Karin AA, Matić S, Barać J, Benasić T, Stiglmayer N: Quality of life in patients with blepharospasm. Coll Antropol 2013;37:29–33. 5 Elston JS, Marsden CD, Grandas F, Quinn NP: The significance of ophthalmological symptoms in idiopathic blepharospasm. Eye (Lond) 1988;2:435–439.
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
6 Grandas F, Elston J, Quinn N, Marsden CD: Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry 1988;51:767–772. 7 Defazio G, Livrea P: Epidemiology of primary blepharospasm. Mov Disord 2002;17:7–12. 8 Peckham EL, Lopez G, Shamim EA, Richardson SP, Sanku S, Malkani R, et al: Clinical features of patients with blepharospasm: a report of 240 cases. Eur J Neurol 2011;18:382–386.
Huang/Wang/Liang/Du/Zhou
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
References
Clinical Analysis of Patients with Primary Blepharospasm in China
12 Davide M, Giovanni D, Giovanni A, et al: Relationship between eye symptoms and blepharospasm: a multicenter case-control study. Mov Disord 2005;20:1564–1570. 13 Defazio G, Abbruzzese G, Aniello MS, Di Fede R, Esposito M, Fabbrini G, et al: Eye symptoms in relatives of patients with primary adult-onset dystonia. Mov Disord 2012;27: 305–307. 14 Martino D, Liuzzi D, Macerollo A, Aniello MS, Livrea P, Defazio G: The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia. Mov Disord 2010;25:407–412. 15 Loyola DP, Camargos S, Maiaand D, Cardoso F: Sensory tricks in focal dystonia and hemifacial spasm. Eur J Neurol 2013;20:704–707.
16 Hara K, Matsuda A, Kitsukawa Y, Tanaka K, Nishizawa M, Tagawa A: Botulinum toxin treatment for blepharospasm associated with myasthenia gravis. Mov Disord 2007; 22: 1363–1364. 17 Fabbrini G, Berardelli I, Moretti G, Pasquini M, Bloise M, Colosimo C: Psychiatric disorders in adult-onset focal dystonia: a case-control study. Mov Disord 2010;25:459–465. 18 Drake DD, Erik CB: Additional clinical observations on psychiatric disorders in adult-onset focal dystonia: a case control study. Mov Disord 2011;26:1572; author reply 1573.
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
341
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
9 Defazio G, Martino D, Aniello MS, Masi G, Abbruzzese G, Lamberti S, Valente EM, Brancati F, Livrea P, Berardelli A: A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry 2006;77:252–254. 10 Kazuo T, Tsutomu F: Dry eye and Meige’s syndrome. Br J Ophthalmol 1997; 81: 439– 442. 11 Lu R, Huang R, Li K, Zhang X, Yang H, Quan Y, Li Q: The influence of benign essential blepharospasm on dry eye disease and ocular inflammation. Am J Ophthalmol 2014; 157: 591–597.e1–e2.
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases in China Xiao-Feng Huang a Kai-Yue Wang b Zhan-Hua Liang a Rong-Rong Du c Li-Na Zhou a
a
Department of Neurology, First Affiliated Hospital of Dalian Medical University, Dalian, b Department of Neurology, Linyi City People’s Hospital, Linyi and c Department of Neurology, First Affiliated Hospital of Baotou Medical College, Baotou, China
Abstract Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. Results: The age of onset was 56.4 ± 2.7 (range, 32– 76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2–120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. Conclusions: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0014–3022/15/0736–0337$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
Primary blepharospasm (PBS) is a focal dystonia that often begins insidiously and progressively worsens. Blepharospasm is characterized by excessive involuntary narrowing or closing of the eyelids; it frequently results in eyelid closure and visual disability [1]. It usually appears in adults and more frequently affects female. Severe blepharospasm has a disabling effect on work and everyday activities and may cause social embarrassment and catastrophic traffic accidents [2–4]. Patients with blepharospasm often first consult an ophthalmologist. Until recently, only a few reports had been published on the demographic and clinical features of blepharospasm [4–6]. This study explored the demographic and clinical features of blepharospasm in China. The findings of this study should increase the awareness of blepharospasm and improve physicians’ understanding of differential diagnoses. Patients and Methods This retrospective study was conducted at the Botulinum Toxin Injection Special Clinic and Movement Disorders Special Clinic in the First Affiliated Hospital of Dalian Medical University.
Zhan-Hua Liang Department of Neurology First Affiliated Hospital of Dalian Medical University 222 Zhong-shan Road, Dalian 116011, Liaoning Province (China) E-Mail zhanhualiang @ 163.com
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
Key Words Focal dystonia · Blepharospasm · Dry eyes · Photophobia · Myasthenia gravis · Botulinum toxin
Results
Seventy-two female (72%) and 28 male (28%) patients participated in this study. The female:male ratio was 2.6:1. The mean age of onset was 56.4 ± 2.7 (range, 32–76 years). The mean duration between the time of onset to the time of accurate diagnosis was 38.7 ± 36.0 months (range, 2–120 months). The age of blepharospasm onset was prior or at 40 in 12% of patients, between the ages of 41 and 50 in 14%, between the ages of 51 and 60 in 44%, between the ages of 61 and 70 in 24%, and older than 70 years old in 6%. Seventy-three patients (73%) had emotional incentives, including depression and anxiety. Twenty-three percent of the patients had merged oromandibular dystonia (OMD), one patient had merged cervical dystonia (CD), two patients had merged Parkinson’s disease, and one patient had an accompanied tic. Five patients (5%) had a family history of movement disorders such as Parkinson’s disease and essential tremor (table 1). The most frequent complaints were dry eyes, difficulty in opening the eye, increased blinking, and photophobia (table 2). The time intervals between initial symptoms to obvious orbicularis oculi muscle spasms were as follows (median time): eyelid twitching, 18 months (range, 1–36 months); dry mouth, 18 months (1–36 months); increased blinking, 12 months (range, 1–60 months); difficulty in opening the eyes, 12 months (range, 1–60 months); dry eyes, 11 months (range, 0.5–24 months); and photophobia, 6 months (range, 1–12 months). Most patients simultaneously or successively developed several symptoms. Twenty-seven percent of the patients had both photophobia and difficulty in eye opening, and 20% had both eye fatigue and dry eyes. Seventy-five percent of patients chose to first consult an ophthalmologist. Only 10% of the patients were correctly diagnosed at the first counseling. Eighteen patients had progressed to functional blindness before an accurate diagnosis was made. The most frequent initial diagnoses were dry eye syndrome, conjunctivitis/keratitis, and myasthenia gravis (MG) (table 3). Of those who first saw an ophthalmologist, 34 patients were initially diagnosed with dry eye syndrome, and 27 were initially diag338
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
Table 1. The demographic and clinical characteristics of blepharospasm patients
Male:female Age at onset, years Symptom duration before accurate diagnosis, months Sensory tricks Emotional disorders Simple PBS PBS + OMD PBS + PD PBS + CD PBS + Tic Family history
28:72 (1:2.6) 56.4±2.7 (32–76) 38.7±36.0 (2–120) 86 73 73 23 2 1 1 5
Table 2. The early symptoms of blepharospasm patients (100 pa-
tients) Early symptoms
No. of patients*
The median time to develop spasm, months
Dry eyes Difficulty of eye opening Increased blinking Photophobia Eyelid twitching Dry mouth Eye pain Facial discomfort Cervical tight Nasal discomfort
54 39 32 32 15 13 9 5 5 4
11 12 12 6 18 18 6 10 7 1
* Many patients simultaneously or successively developed more than one symptom.
Table 3. Number of patients originally misdiagnosed with other
diseases Misdiagnosed diseases
No. of patients (%)
Dry eye syndrome Conjunctivitis/keratitis Myasthenia gravis Neurosis Ametropia Rhinitis Sjogren syndrome
34 (34) 27 (27) 14 (14) 9 (9) 5 (5) 2 (2) 1 (1)
nosed with conjunctivitis/keratitis. Of the patients who first saw a neurologist, 8 were diagnosed with blepharospasm, 7 with myasthenia gravis, and 9 with neurosis. Myasthenia gravis was the secondary tentative diagnosis for 7 cases of patient. In summary, 14 patients of the 100 Huang/Wang/Liang/Du/Zhou
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
From March 2010 to December 2013, 100 patients with blepharospasm were enrolled in this study. Data were collected from medical records and face-to-face interviews with the patients and their families. This study was approved by the Institutional Review Board of the First Affiliated Hospital of Dalian Medical University.
This study retrospectively analyzed 100 patients with primary blepharospasm in China. The results supported previous findings in blepharospasm patients with an average age at the time of onset being in the range of 50 to 60 [3, 6, 7]. The female:male ratio was 2.6:1. This ratio was similar in two previous reports [3, 8] but was higher than that reported by Grandas (1.8:1) [6]. In this study, most of the patients did not receive the correct diagnosis in a timely manner, and the mean duration between onset and accurate diagnosis was more than 3 years. Recently, a study from Italy showed that even in recent years, reaching the correct diagnosis took >1 year in nearly half of patients [8]. Twenty-three percent of the patients had merged OMD, which was a lower rate than that reported by Peckham of 32% [8]. According to previous studies, 7–32% of adult-onset probands had at least one firstdegree relative with dystonia [6, 8, 9]. However, we found that none of the patients with blepharospasm had a family history of any type of dystonia, and only 5% patients had a family history of other movement disorders. Our results suggested that genetic background was not a significant factor in the pathogenesis of adult-onset PBS in the Chinese population. We found that the most frequent symptoms were dry eyes, difficulty in eye opening, increased blinking and photophobia. Dry eye syndrome was a common ophthal-
mological diagnosis for blepharospasm patients. Previous studies showed that dry eyes presented in 40–60% of PBS patients; these findings were consistent with the results of this study [5, 6]. Recently, a study from Asia reported that dry eyes only occurred in 18.9% of patients with PBS [3]. One study [10] followed up 324 cases of new-onset patients with dry eyes; 28 (57%) of the treatment-unresponsive patients were diagnosed with Meige syndrome. Rong’s [11] studies reported that blepharospasm increased dry eyes and other eye inflammation, but focal botulinum toxin injection could relieve these symptoms. Thirty-two of the patients had photophobia, a condition in which bright light from various sources induced irritating ocular discomfort and increased spasms and made it more difficult for the patients to open their eyes; wearing tinted glasses or a hat has a positive effect on these symptoms. Bright light prevented patients from going outdoors alone during the day and at night. Patients noticed that using tinted glasses or a windshield helped relieve their symptoms. This finding was similar with that of another study from Asia [3]. However, Peckham et al. [8] investigated 240 PBS patients (93% Caucasian) and found that only 25% of the patients had photophobia. The inconsistent results may be due to different races of the study population. Moreover, Wen-Juh Hwang reported that only 11% of the patients spontaneously complained of photophobia, but upon questioning, 97% of the patients had photophobia [3]. Eye symptoms associated with PBS result from eye diseases and may be involved in the pathogenesis of PBS [12]. The first-degree relatives of blepharospasm patients more frequently had eye symptoms such as dry eyes and gravel and burning sensations [13]. This study showed that 86% of patients with primary blepharospasm experienced sensory tricks. This figure was similar to the results reported by Peckham et al. [8] and Martino et al. [14], who reported sensory tricks in 87 and 71.2% of patients, respectively. Another study from Brazil reported sensory tricks in only 55% of PBS patients [15]. The tricks used by our patients were similar to those described in the literature [14, 15], including wearing sunglasses, pressing on the forehead or jaw, touching their eyelids, chewing and talking. Although rarely reported, myasthenia gravis is a common diagnosis made by neurologists in patients with blepharospasm [3]. In this study, 14 of the patients with blepharospasm were diagnosed with MG. The difficulty in eye opening is similar to ptosis. The common features for both myasthenia gravis and blepharospasm include predominant eyelid involvement, sleep benefits,
Clinical Analysis of Patients with Primary Blepharospasm in China
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
Discussion
339
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
patients (14%) were originally suspected to have myasthenia gravis. Patients diagnosed with dry eye syndrome accepted regular ophthalmic treatments such as eye drops, which had no effect or had a mild effect. All of the patients who were diagnosed with myasthenia gravis had received a single test or a combination of tests related to myasthenia gravis. Four patients showed a false positive result in a neostigmine test. One patient underwent thymectomy surgery. Patients who were diagnosed with neurosis received anti-anxiety drugs, anti-depression drugs or repetitive transcranial magnetic stimulation therapy. Seven patients who reported both mental and spasm symptoms experienced mild-to-moderate beneficial effects lasting no longer than 3 months. These patients received botulinum toxin type A injections (50–100 IU) in our movement disorder clinic. The duration of the effect of botulinum toxin type A was longer than 3 months in 93 (93%) patients. The mean interval between injections was 5.2 ± 1.6 months (range, 3–10 months).
diurnal changes, relief by rest or local cold water packing, excessive blinking, and photophobia. Although the positive rate of repetitive nerve stimulation (RNS) is up to 80% in general MG, the rate is only 17.2% in simple ocular MG. There are very few patients with comorbid myasthenia gravis and blepharospasm [15, 16]. Considering that botulinum toxin can aggravate muscle weakness in MG, myasthenia gravis should be optimally treated before considering using botulinum toxin in patients with coexisting myasthenia gravis and blepharospasm. Fabbrini et al. [17] reported that 19/28 patients (67.9%) with PBS had anxiety and/or depressive symptoms. After that, a case-control study from the United States reported a higher rate (82%) of anxiety and/or depressive disorders in patients with PBS [18]. The most common psychiatric feature in patients with BPS is depressive disorder [17]. In this study, 73% of the patients experienced negative emotions such as high pressure at work pressure, life stress and death of relatives before disease onset. Most patients had mild to severe anxiety or depression in the early stage, and oral anti-anxiety or anti-depressant medications can relieve both psychiatric symptoms and spasms. In some patients, psychiatric symptoms occurred before or increased with the progression of blepharospasm. In this study, patients diagnosed with psychiatric disorders received oral anti-anxiety and/or anti-depression medications. The spasms and psychiatric symptoms were mildly to moderately improved, but effects were not long lasting. Based on our experience, patients with combined blepharospasm and depression or anxiety experienced a shorter duration of efficacy of botulinum toxin. For such patients, oral medications were helpful in prolonging the efficacy of botulinum toxin. Psychiatric disorders may share a common pathophysiology with dystonia or may arise as a reaction to dystonia [4, 17, 18]. This study has the following significance: (1) the clinical manifestations of blepharospasm vary, and the rate of
accurate diagnosis is very low. Some patients progress to functional blindness, are unable to live and work independently, and even develop suicidal ideations; (2) the ability to differentiate blepharospasm from dry eye syndrome by ophthalmologists must be improved; (3) in some cases, ocular MG and PBS are difficult to identify, and it is thus recommended that MG is considered first and closely followed up; (4) anxiety and depression symptoms may be the early symptoms of blepharospasm and should be closely observed, and (5) local botulinum toxin type A injections are safe and effective to treat blepharospasm. In summary, the early clinical manifestations of blepharospasm include dry eyes (54%), difficulty of eye opening (39%), increased blinking (32%) and photophobia (32%). The majority of patients consulted an ophthalmologist at first. The most frequently diagnosed diseases were dry eye syndrome, conjunctivitis/keratitis, MG and neurosis. Our study showed that it is necessary for ophthalmologists and neurologists to improve their understanding of blepharospasm, which will be of great benefit for accurately diagnosing and treating patients in a timely manner and for preventing the progression to functional blindness.
Acknowledgment This study was supported by Liaoning Province Natural Science Foundation-funded Project (No. 201102052).
Disclosure Statement We declare that we have no financial and personal relationships with other people or organizations that could inappropriately influence our work. There are no professional or other personal interests of any nature or type in any product, service and/or company that could be construed as having influenced the conclusions presented in or the review of this manuscript.
1 Hallett M, Evinger C, Jankovic J, Stacy M: Update on blepharospasm: report from the BEBRF international workshop. Neurology 2008;71:1275–1282. 2 Hwang WJ, Tsai CF: Motor vehicle accidents and injuries in patients with idiopathic blepharospasm. J Neurol Sci 2014;339:217–219. 3 Hwang WJ: Demographic and clinical features of patients with blepharospasm in
340
southern Taiwan: a university hospital-based study. Acta Neurol Taiwan 2012;21:108–114. 4 Biuk D, Karin AA, Matić S, Barać J, Benasić T, Stiglmayer N: Quality of life in patients with blepharospasm. Coll Antropol 2013;37:29–33. 5 Elston JS, Marsden CD, Grandas F, Quinn NP: The significance of ophthalmological symptoms in idiopathic blepharospasm. Eye (Lond) 1988;2:435–439.
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
6 Grandas F, Elston J, Quinn N, Marsden CD: Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry 1988;51:767–772. 7 Defazio G, Livrea P: Epidemiology of primary blepharospasm. Mov Disord 2002;17:7–12. 8 Peckham EL, Lopez G, Shamim EA, Richardson SP, Sanku S, Malkani R, et al: Clinical features of patients with blepharospasm: a report of 240 cases. Eur J Neurol 2011;18:382–386.
Huang/Wang/Liang/Du/Zhou
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
References
Clinical Analysis of Patients with Primary Blepharospasm in China
12 Davide M, Giovanni D, Giovanni A, et al: Relationship between eye symptoms and blepharospasm: a multicenter case-control study. Mov Disord 2005;20:1564–1570. 13 Defazio G, Abbruzzese G, Aniello MS, Di Fede R, Esposito M, Fabbrini G, et al: Eye symptoms in relatives of patients with primary adult-onset dystonia. Mov Disord 2012;27: 305–307. 14 Martino D, Liuzzi D, Macerollo A, Aniello MS, Livrea P, Defazio G: The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia. Mov Disord 2010;25:407–412. 15 Loyola DP, Camargos S, Maiaand D, Cardoso F: Sensory tricks in focal dystonia and hemifacial spasm. Eur J Neurol 2013;20:704–707.
16 Hara K, Matsuda A, Kitsukawa Y, Tanaka K, Nishizawa M, Tagawa A: Botulinum toxin treatment for blepharospasm associated with myasthenia gravis. Mov Disord 2007; 22: 1363–1364. 17 Fabbrini G, Berardelli I, Moretti G, Pasquini M, Bloise M, Colosimo C: Psychiatric disorders in adult-onset focal dystonia: a case-control study. Mov Disord 2010;25:459–465. 18 Drake DD, Erik CB: Additional clinical observations on psychiatric disorders in adult-onset focal dystonia: a case control study. Mov Disord 2011;26:1572; author reply 1573.
Eur Neurol 2015;73:337–341 DOI: 10.1159/000381707
341
Downloaded by: Dahlgree Med. Library, Goergetown Univ. 141.161.91.14 - 5/25/2015 4:28:48 AM
9 Defazio G, Martino D, Aniello MS, Masi G, Abbruzzese G, Lamberti S, Valente EM, Brancati F, Livrea P, Berardelli A: A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry 2006;77:252–254. 10 Kazuo T, Tsutomu F: Dry eye and Meige’s syndrome. Br J Ophthalmol 1997; 81: 439– 442. 11 Lu R, Huang R, Li K, Zhang X, Yang H, Quan Y, Li Q: The influence of benign essential blepharospasm on dry eye disease and ocular inflammation. Am J Ophthalmol 2014; 157: 591–597.e1–e2.
