Blepharospasm

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Blepharospasm
Other namesEye dystonia, Eye twitching, Eye spasm
Pronunciation
Specialty Neurology, ophthalmology

Blepharospasm is a neurological disorder characterized by intermittent, involuntary spasms and contractions of the orbicularis oculi (eyelid) muscles around both eyes. [1] [2] [3] [4] These result in abnormal twitching or blinking, and in the extreme, sustained eyelid closure resulting in functional blindness.

Contents

The word blepharospasm is derived from the Greek: βλέφαρον / blepharon, eyelid, and σπασμός / spasmos, spasm, an uncontrolled muscle contraction. The condition should be distinguished from the more common, and milder, involuntary quivering of an eyelid, known as myokymia or fasciculation.

Blepharospasm is one form of a group of movement disorders called dystonia. [4] It may be a primary or secondary disorder. The primary disorder is benign essential blepharospasm, in which term the qualifier essential indicates that the cause is unknown. Blepharospasm may occur as secondary to conditions including dry eyes and other specific ocular disease or conditions, Meige's Syndrome and other forms of dystonia, and Parkinson's Disease and other movement disorders. [3]

Blepharospasm occurs in middle age and is more frequent among women than men. The most common treatments are medication and periodic injections of botulinum toxin into the eyelid muscles.

Epidemiology

Blepharospasm is a fairly rare disease. Estimates of incidence and prevalence vary, tending to be higher in population studies than service studies, [5] likely because of delays in diagnosis. [4] In the United States, approximately 2,000 new cases of blepharospasm are diagnosed each year. [6] Estimates of incidence per million persons-years range from 14.5 in Northern California [7] to 100 in Taiwan. [8] Estimates of prevalence per million range from 12 in Olmsted County, Minnesota [9] to 133 in Puglia, Southern Italy. [10]

The onset of blepharospasm tends to be during the ages 40–60. [8] [10] [11] The condition is roughly more than twice as frequent among females than males, [7] [8] [11] which may be related to menopause and hormone treatments. [12] [13] In Taiwan, the condition is more frequent among white- than blue-collar workers. [8]

Signs and symptoms

Blepharospasm usually begins with occasional twitches of both eyelids, which progress over time to forceful and frequent spasms and contractions of the eyelids. In severe episodes, the patient cannot open their eyelids (apraxia), which severely limits their daily activities. Prolonged closure of the eyelids may result in functional blindness. [4]

Patients suffering from blepharospasm also report sensory symptoms including sensitivity to light, [14] [15] dry eyes, [16] and burning sensation and grittiness in the eyes. [4] Although such symptoms tend to precede the onset of the blepharospasm, they may both be due to a common third factor. [17]

Typically, the symptoms—spasms and contractions of the eyelids—tend to worsen when the patient relaxes but abate during sleep. [18] The symptoms may be temporarily alleviated by sensory tricks (geste antagoniste) including stretching or rubbing the eyebrows, eyelids, or forehead, [19] and singing, talking, or humming. [20] Blepharospasm is aggravated by fatigue, stress, and environmental factors such as wind or air pollution. [21]

Although blepharospasm is defined as a bilaterally symmetric disorder that affects both eyes, some research has reported unilateral onset. [11] [22]

Causes

Historically, it was believed that blepharospasm was due to the abnormal functioning of the brain's basal ganglia. [23] The basal ganglia are structures in the brain that are involved in the regulation of motor and reward functions.

However, blepharospasm is now known to involve several regions of the brain and to be a multifactorial condition in which "one or several as yet unknown genes together with epigenetic and environmental factors combine to reach the threshold that induces the disease". [3]

Blepharospasm is often associated with dry eyes, but the causal mechanism is still not clear. [16] [8] Research in New York and Italy suggests that increased blinking (which may be triggered by dry eyes) leads to blepharospasm. [24] [25] A case control study in China found that blepharospasm aggravated dry eyes. [26]

Blepharospasm may be associated with dystonia in other parts of the body, particularly Meige's Syndrome. [27] [28] [4] Blepharospasm may be associated with Parkinson's Disease, but the causal mechanism is still not clear. [29] [30] In rare cases, blepharospasm is associated with multiple sclerosis. [31] [32]

Some drugs can induce blepharospasm, including those used to treat depression [33] [34] and Parkinson's disease. [35] Hormone replacement therapy for women going through menopause has been found to be associated with dry eyes, [13] which in turn is associated with blepharospasm.

Blepharospasm can be caused by concussions in some rare cases, when a blow to the back of the head damages the basal ganglia. [36]

Blepharospasm is associated with exposure to the sun. [37]

Diagnosis

No laboratory tests exist with which to definitively diagnose blepharospasm. Historically, the condition was frequently misdiagnosed, [18] often as a psychiatric condition. [6]

Diagnosis of blepharospasm has been enhanced by the proposal of objective diagnostic criteria that start from "stereotyped, bilateral and synchronous orbicularis oculi spasms" and proceed to the identification of a "sensory trick" or "increased blinking". [38] The criteria have been validated across multiple ethnicities in multiple centers. [39]

Treatment

Standard first line treatments of blepharospasm are conservative therapies, oral medication, and periodic injections of botulinum toxin.

Particularly when associated with dry eyes, blepharospasm may be relieved with warm compresses, eye drops, and eye wipes. [40] [41] A Japanese study showed that warm compresses containing menthol were more effective in increasing tear film. [42]

Drugs used to treat blepharospasm are anticholinergics, benzodiazepines, baclofen, and tetrabenazine. [43] The proportion of patients who benefited from anticholinergics ranged from 1 in 9 in Oregon [44] to 1 in 5 in England. [11] Besides failing to resolve the blepharospasm, some drugs present the risk of side effects. In Japan, use of etizolam and benzodiazepine was associated with the development of blepharospasm. [33] [34] A case report from Sri Lanka suggests treatment with Mosapride. [45]

The main first-line therapy is periodic injections of botulinum toxin type A to induce localized, partial paralysis of the eyelid muscles. [46] [47] Injections are generally administered at intervals of around 10 weeks, with variations based on patient response and usually give fairly quick relief from the muscle spasms. An English study reported that 118 (78%) of 151 patients experienced significant relief of symptoms for a mean duration of 9.2 weeks. [11] However, in a minority of patients, the injections do not provide any symptomatic relief. Injections of botulinum toxin may diminish in effectiveness with prolonged use and require increased dosage. [48] Injections of botulinum toxin increase the risk of visual complaints and ptosis (eyelid droop). [46]

Patients who do not respond well to medication or botulinum toxin injections are candidates for surgical therapy. The most effective surgical treatment has been protractor myectomy, the removal of muscles responsible for eyelid closure. [49] Myectomy is more effective than distal neurectomy. [50]

A case report from California suggests the use of intense pulsed light therapy to relieve blepharospasm. [51] Patients suffering from blepharospasm may get relief by wearing spectacles fitted to lift the upper eyelid. [43] Among complementary therapies, two simulate sensory tricks: Attaching a device to spectacle frames to press on the patient's temple, [52] and applying thin cosmetic tapes to the forehead and eyebrows. [53] Another complementary therapy is retraining the brain to "rewire" itself and eliminate dystonic movements. Associated with Joaquin Farias, sensorimotor retraining activities and proprioceptive stimulation aim to induce neuroplasticity, making it possible for patients to recover substantial function that was lost due to blepharospasm. [54] Complementary therapies lack evidence of the highest quality (Level 1).

Research

The U.S. National Library of Medicine maintains a register of clinical trials of therapies to treat blepharospasm.

Multimedia

Blepharospasm Research Foundation

Neuroplasticity training

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References

  1. Hallett, Mark (12 November 2002). "Blepharospasm: Recent advances". Neurology. 59 (9): 1306–1312. doi:10.1212/01.WNL.0000027361.73814.0E. ISSN   0028-3878. PMID   12434791.
  2. Hallett, Mark; Evinger, Craig; Jankovic, Joseph; Stacy, Mark (14 October 2008). "Update on blepharospasm". Neurology. 71 (16): 1275–1282. doi:10.1212/01.wnl.0000327601.46315.85. ISSN   0028-3878. PMC   2676990 . PMID   18852443.
  3. 1 2 3 Defazio, Giovanni; Hallett, Mark; Jinnah, Hyder A.; Conte, Antonella; Berardelli, Alfredo (10 February 2017). "Blepharospasm 40 years later". Movement Disorders. 32 (4): 498–509. doi:10.1002/mds.26934. ISSN   0885-3185. PMC   5941939 . PMID   28186662.
  4. 1 2 3 4 5 6 Scorr, Laura M.; Cho, Hyun Joo; Kilic-Berkmen, Gamze; McKay, J. Lucas; Hallett, Mark; Klein, Christine; Baumer, Tobias; Berman, Brian D.; Feuerstein, Jeanne S.; Perlmutter, Joel S.; Berardelli, Alfredo; Ferrazzano, Gina; Wagle-Shukla, Aparna; Malaty, Irene A.; Jankovic, Joseph (16 May 2022). "Clinical Features and Evolution of Blepharospasm: A Multicenter International Cohort and Systematic Literature Review". Dystonia. 1. doi: 10.3389/dyst.2022.10359 . ISSN   2813-2106. PMC   9557246 . PMID   36248010.
  5. Steeves, Thomas D.; Day, Lundy; Dykeman, Jonathan; Jette, Nathalie; Pringsheim, Tamara (31 October 2012). "The prevalence of primary dystonia: A systematic review and meta-analysis". Movement Disorders. 27 (14): 1789–1796. doi:10.1002/mds.25244. ISSN   0885-3185. PMID   23114997.
  6. 1 2 Simon, Guy J. Ben; McCann, John D. (Summer 2005). "Benign Essential Blepharospasm". International Ophthalmology Clinics. 45 (3): 49–75. doi:10.1097/01.iio.0000167238.26526.a8. ISSN   0020-8167. PMID   15970766.
  7. 1 2 Byrd, Erica; Albers, Kathleen; Goldman, Samuel; Klingman, Jeffrey; Lo, Raymond; Marras, Connie; Leimpeter, Amethyst; Fross, Robin; Comyns, Kathleen; Gu, Zhuqin; Katz, Maya; Ozelius, Laurie; Bressman, Susan; Saunders-Pullman, Rachel; Comella, Cynthia (5 April 2016). "Blepharospasm in a Multiethnic Population (P3.348)". Neurology. 86 (16_supplement). doi:10.1212/wnl.86.16_supplement.p3.348. ISSN   0028-3878.
  8. 1 2 3 4 5 Sun, Yng; Tsai, Pei-Jhen; Chu, Chin-Liang; Huang, Wei-Chun; Bee, Youn-Shen (26 December 2018). "Epidemiology of benign essential blepharospasm: A nationwide population-based retrospective study in Taiwan". PLOS ONE. 13 (12): e0209558. Bibcode:2018PLoSO..1309558S. doi: 10.1371/journal.pone.0209558 . ISSN   1932-6203. PMC   6306223 . PMID   30586395.
  9. Bradley, Elizabeth A.; Hodge, David O.; Bartley, George B. (May 2003). "Benign Essential Blepharospasm Among Residents of Olmsted County, Minnesota, 1976 to 1995: An Epidemiologic Study". Ophthalmic Plastic & Reconstructive Surgery. 19 (3): 177–181. doi:10.1097/01.IOP.0000065203.88182.CF. ISSN   0740-9303. PMID   12918550.
  10. 1 2 Defazio, G.; Livrea, P.; De Salvia, R.; Manobianca, G.; Coviello, V.; Anaclerio, D.; Guerra, V.; Martino, D.; Valluzzi, F.; Liguori, R.; Logroscino, G. (12 June 2001). "Prevalence of primary blepharospasm in a community of Puglia region, Southern Italy". Neurology. 56 (11): 1579–1581. doi:10.1212/wnl.56.11.1579. ISSN   0028-3878. PMID   11402121.
  11. 1 2 3 4 5 Grandas, F; Elston, J; Quinn, N; Marsden, C D (1 June 1988). "Blepharospasm: a review of 264 patients". Journal of Neurology, Neurosurgery & Psychiatry. 51 (6): 767–772. doi:10.1136/jnnp.51.6.767. ISSN   0022-3050. PMC   1033145 . PMID   3404184.
  12. Martino, Davide; Livrea, Paolo; Giorelli, Maurizio; Masi, Gianluca; Aniello, Maria Stella; Defazio, Giovanni (2002). "Menopause and Menarche in Patients with Primary Blepharospasm: An Exploratory Case-Control Study". European Neurology. 47 (3): 161–164. doi:10.1159/000047975. ISSN   0014-3022. PMID   11914554.
  13. 1 2 Liesegang, Thomas J (March 2002). "Hormone replacement therapy and dry eye syndrome. Schaumberg DA,∗∗Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Ave E, Boston, MA 02215. USA E-mail: schaumberg@rics.bwh.harvard.edu Buring JE, Sullivan DA, Dana MR. JAMA 2001;286:2114–2119". American Journal of Ophthalmology. 133 (3): 435–436. doi:10.1016/s0002-9394(02)01368-5. ISSN   0002-9394.
  14. Adams WH, Digre KB, Patel BC, Anderson RL, Warner JE, Katz BJ (July 2006). "The evaluation of light sensitivity in benign essential blepharospasm". American Journal of Ophthalmology. 142 (1): 82–87. doi:10.1016/j.ajo.2006.02.020. PMID   16815254.
  15. Molloy, Anna; Williams, Laura; Kimmich, Okka; Butler, John S; Beiser, Ines; McGovern, Eavan; O'Riordan, Sean; Reilly, Richard B; Walsh, Cathal; Hutchinson, Michael (22 April 2015). "Sun exposure is an environmental factor for the development of blepharospasm". Journal of Neurology, Neurosurgery & Psychiatry. 87 (4): 420–424. doi:10.1136/jnnp-2014-310266. ISSN   0022-3050. PMID   25904812.
  16. 1 2 Elsron, J S; Marsden, C D; Grandas, F; Quinn, N P (July 1988). "The significance of ophthalmological symptoms in idiopathic blepharospasm". Eye. 2 (4): 435–439. doi:10.1038/eye.1988.79. ISSN   0950-222X. PMID   3253136.
  17. Defazio, Giovanni; Abbruzzese, Giovanni; Stella Aniello, Maria; Di Fede, Roberta; Esposito, Marcello; Fabbrini, Giovanni; Girlanda, Paolo; Liguori, Rocco; Marinelli, Lucio; Martino, Davide; Morgante, Francesca; Santoro, Lucio; Tinazzi, Michele; Berardelli, Alfredo (15 December 2011). "Eye symptoms in relatives of patients with primary adult-onset dystonia". Movement Disorders. 27 (2): 305–307. doi:10.1002/mds.24026. ISSN   0885-3185. PMID   22173654.
  18. 1 2 Defazio, Giovanni; Livrea, Paolo (2004). "Primary Blepharospasm". Drugs. 64 (3): 237–244. doi:10.2165/00003495-200464030-00002. ISSN   0012-6667. PMID   14871168.
  19. Martino, Davide; Liuzzi, Daniele; Macerollo, Antonella; Aniello, Maria Stella; Livrea, Paolo; Defazio, Giovanni (15 March 2010). "The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia". Movement Disorders. 25 (4): 407–412. doi:10.1002/mds.23011. ISSN   0885-3185. PMID   20108367.
  20. Peckham, E. L.; Lopez, G.; Shamim, E. A.; Richardson, S. Pirio; Sanku, S.; Malkani, R.; Stacy, M.; Mahant, P.; Crawley, A.; Singleton, A.; Hallett, M. (17 February 2011). "Clinical features of patients with blepharospasm: a report of 240 patients". European Journal of Neurology. 18 (3): 382–386. doi:10.1111/j.1468-1331.2010.03161.x. ISSN   1351-5101. PMC   3934127 . PMID   20649903.
  21. Coscarelli, Jandira Mourão (May 2010). "Essential Blepharospasm". Seminars in Ophthalmology. 25 (3): 104–108. doi:10.3109/08820538.2010.488564. ISSN   0882-0538. PMID   20590421.
  22. Hwang, WJ (2012). "Demographic and Clinical Features of Patients with Blepharospasm in Southern Taiwan: a university Hospital-Based Study". Acta Neurol Taiwan. 21 (3): 108–114. PMID   23196730.
  23. Marsden, C D (1 December 1976). "Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). A variant of adult-onset torsion dystonia?". Journal of Neurology, Neurosurgery & Psychiatry. 39 (12): 1204–1209. doi:10.1136/jnnp.39.12.1204. ISSN   0022-3050. PMC   492566 . PMID   1011031.
  24. Evinger, Craig; Bao, Jian-Bin; Powers, Alice S.; Kassem, Iris S.; Schicatano, Edward J.; Henriquez, Victor M.; Peshori, Kavita R. (31 January 2002). "Dry eye, blinking, and blepharospasm". Movement Disorders. 17 (S2): S75–S78. doi:10.1002/mds.10065. ISSN   0885-3185. PMC   3327285 . PMID   11836761.
  25. Conte, Antonella; Ferrazzano, Gina; Defazio, Giovanni; Fabbrini, Giovanni; Hallett, Mark; Berardelli, Alfredo (2 June 2017). "Increased Blinking May Be a Precursor of Blepharospasm: A Longitudinal Study". Movement Disorders Clinical Practice. 4 (5): 733–736. doi:10.1002/mdc3.12499. ISSN   2330-1619. PMC   5654574 . PMID   29082270.
  26. Lu, Rong; Huang, Ruisheng; Li, Kang; Zhang, Xinchun; Yang, Hui; Quan, Yadan; Li, Qian (March 2014). "The Influence of Benign Essential Blepharospasm on Dry Eye Disease and Ocular Inflammation". American Journal of Ophthalmology. 157 (3): 591–597.e2. doi:10.1016/j.ajo.2013.11.014. ISSN   0002-9394. PMID   24269849.
  27. Jankovic, Joseph; Ford, Janet (April 1983). "Blepharospasm and orofacial-cervical dystonia: Clinical and pharmacological findings in 100 patients". Annals of Neurology. 13 (4): 402–411. doi:10.1002/ana.410130406. ISSN   0364-5134. PMID   6838174.
  28. Abbruzzese, G; Berardelli, A; Girlanda, P; Marchese, R; Martino, D; Morgante, F; Avanzino, L; Colosimo, C; Defazio, G (1 April 2008). "Long-term assessment of the risk of spread in primary late-onset focal dystonia". Journal of Neurology, Neurosurgery & Psychiatry. 79 (4): 392–396. doi:10.1136/jnnp.2007.124594. ISSN   0022-3050. PMID   17635969.
  29. Micheli, Federico; Scorticati, María Clara; Folgar, Silvia; Gatto, Emilia (September 2004). "Development of Parkinson's disease in patients with blepharospasm". Movement Disorders. 19 (9): 1069–1072. doi:10.1002/mds.20084. ISSN   0885-3185. PMID   15372598.
  30. Rana, Abdul-Qayyum; Kabir, Ashish; Dogu, Okan; Patel, Ami; Khondker, Sumaiya (11 October 2012). "Prevalence of Blepharospasm and Apraxia of Eyelid Opening in Patients with Parkinsonism, Cervical Dystonia and Essential Tremor". European Neurology. 68 (5): 318–321. doi:10.1159/000341621. ISSN   0014-3022. PMID   23075668.
  31. Nociti, V; Bentivoglio, Ar; Frisullo, G; Fasano, A; Soleti, F; Iorio, R; Loria, G; Patanella, Ak; Marti, A; Tartaglione, T; Tonali, Pa; Batocchi, Ap (November 2008). "Movement disorders in multiple sclerosis: causal or coincidental association?". Multiple Sclerosis Journal. 14 (9): 1284–1287. doi:10.1177/1352458508094883. ISSN   1352-4585. PMID   18768580.
  32. Edechi, Chidalu A.; Micieli, Jonathan A. (28 April 2022). "Blepharospasm and Sixth Nerve Palsy as the Presenting Sign of Multiple Sclerosis". Journal of Neuro-Ophthalmology: 10.1097/WNO.0000000000001916. doi:10.1097/WNO.0000000000001916. ISSN   1070-8022. PMID   37389956.
  33. 1 2 Wakakura M, Tsubouchi T, Inouye J (March 2004). "Etizolam and benzodiazepine induced blepharospasm". Journal of Neurology, Neurosurgery, and Psychiatry. 75 (3): 506–507. doi:10.1136/jnnp.2003.019869. PMC   1738986 . PMID   14966178.
  34. 1 2 Wakakura, M.; Yamagami, A.; Iwasa, M. (3 September 2018). "Blepharospasm in Japan: A Clinical Observational Study From a Large Referral Hospital in Tokyo". Neuro-Ophthalmology. 42 (5): 275–283. doi:10.1080/01658107.2017.1409770. ISSN   0165-8107. PMC   6152494 . PMID   30258472.
  35. Mauriello, Joseph A.; Carbonaro, Paul; Dhillon, Shamina; Leone, Tina; Franklin, Mark (June 1998). "Drug-Associated Facial Dyskinesias—A Study of 238 Patients". Journal of Neuro-Ophthalmology. 18 (2): 153–157. doi:10.1097/00041327-199806000-00016. ISSN   1070-8022. PMID   9621275.
  36. Martino, Davide; Defazio, Giovanni; Abbruzzese, Giovanni; Girlanda, Paolo; Tinazzi, Michele; Fabbrini, Giovanni; Aniello, Maria Stella; Avanzino, Laura; Colosimo, Carlo; Majorana, Giuseppe; Trompetto, Carlo (March 2007). "Head trauma in primary cranial dystonias: a multicentre case–control study". Journal of Neurology, Neurosurgery, and Psychiatry. 78 (3): 260–263. doi:10.1136/jnnp.2006.103713. ISSN   0022-3050. PMC   2117628 . PMID   17056625.
  37. Molloy, Anna; Williams, Laura; Kimmich, Okka; Butler, John S.; Beiser, Ines; McGovern, Eavan; O'Riordan, Sean; Reilly, Richard B.; Walsh, Cathal; Hutchinson, Michael (1 April 2016). "Sun exposure is an environmental factor for the development of blepharospasm". Journal of Neurology, Neurosurgery & Psychiatry. 87 (4): 420–424. doi:10.1136/jnnp-2014-310266. ISSN   0022-3050. PMID   25904812.
  38. Defazio, Giovanni; Hallett, Mark; Jinnah, Hyder A.; Berardelli, Alfredo (16 July 2013). "Development and validation of a clinical guideline for diagnosing blepharospasm". Neurology. 81 (3): 236–240. doi:10.1212/wnl.0b013e31829bfdf6. ISSN   0028-3878. PMC   3770163 . PMID   23771487.
  39. Defazio, Giovanni; Jinnah, Hyder A.; Berardelli, Alfredo; Perlmutter, Joel S.; Berkmen, Gamze Kilic; Berman, Brian D.; Jankovic, Joseph; Bäumer, Tobias; Comella, Cynthia; Cotton, Adam C.; Ercoli, Tommaso; Ferrazzano, Gina; Fox, Susan; Kim, Han-Joon; Moukheiber, Emile Sami (October 2021). "Diagnostic criteria for blepharospasm: A multicenter international study". Parkinsonism & Related Disorders. 91: 109–114. doi:10.1016/j.parkreldis.2021.09.004. ISSN   1353-8020. PMC   9048224 . PMID   34583301.
  40. Murakami, David K.; Blackie, Caroline A.; Korb, Donald R. (September 2015). "All Warm Compresses Are Not Equally Efficacious". Optometry and Vision Science. 92 (9): e327. doi:10.1097/OPX.0000000000000675. ISSN   1538-9235. PMID   26164316.
  41. Defazio, Giovanni; Livrea, Paolo (1 February 2004). "Primary Blepharospasm". Drugs. 64 (3): 237–244. doi:10.2165/00003495-200464030-00002. ISSN   1179-1950. PMID   14871168.
  42. Arita, Reiko; Morishige, Naoyuki; Sakamoto, Ichiro; Imai, Natsuko; Shimada, Yuko; Igaki, Michihito; Suzuki, Atsushi; Itoh, Kouzo; Tsubota, Kazuo (5 April 2017). "Effects of a warm compress containing menthol on the tear film in healthy subjects and dry eye patients". Scientific Reports. 7 (1): 45848. Bibcode:2017NatSR...745848A. doi:10.1038/srep45848. ISSN   2045-2322. PMC   5381094 . PMID   28378793.
  43. 1 2 Vijayakumar, Dhanya; Jankovic, Joseph (4 July 2018). "Medical treatment of blepharospasm". Expert Review of Ophthalmology. 13 (4): 233–243. doi:10.1080/17469899.2018.1503535. ISSN   1746-9899.
  44. Nutt, John G.; Hammerstad, John P.; de Garmo, Pat; Carter, Julie (February 1984). "Cranial dystonia: Double-blind crossover study of anticholinergics". Neurology. 34 (2): 215–217. doi:10.1212/WNL.34.2.215. ISSN   0028-3878. PMID   6363970.
  45. Piyasena INAP; Jayasinghe JAC (March 2014). "Mosapride (5HT4 agonist) in the treatment of blepharospasm". Ceylon Med J. 59 (1): 26–27. doi: 10.4038/cmj.v59i1.5527 . PMID   24682196.
  46. 1 2 Duarte, Gonçalo S; Rodrigues, Filipe B; Marques, Raquel E; Castelão, Mafalda; Ferreira, Joaquim; Sampaio, Cristina; Moore, Austen P; Costa, João (19 November 2020). Cochrane Movement Disorders Group (ed.). "Botulinum toxin type A therapy for blepharospasm". Cochrane Database of Systematic Reviews. 2020 (11): CD004900. doi:10.1002/14651858.CD004900.pub3. PMC   8094161 . PMID   33211907.
  47. Simpson, D. M.; Hallett, M.; Ashman, E. J.; Comella, C. L.; Green, M. W.; Gronseth, G. S.; Armstrong, M. J.; Gloss, D.; Potrebic, S.; Jankovic, J.; Karp, B. P.; Naumann, M.; So, Y. T.; Yablon, S. A. (18 April 2016). "Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology". Neurology. 86 (19): 1818–1826. doi:10.1212/WNL.0000000000002560. PMC   4862245 . PMID   27164716.
  48. Ababneh, Osama H; Cetinkaya, Altug; Kulwin, Dwight R (April 2014). "Long-term efficacy and safety of botulinum toxin A injections to treat blepharospasm and hemifacial spasm". Clinical & Experimental Ophthalmology. 42 (3): 254–261. doi:10.1111/ceo.12165. ISSN   1442-6404. PMID   23844601.
  49. Anderson RL, Patel BC, Holds JB, Jordan DR (September 1998). "Blepharospasm: past, present, and future". Ophthalmic Plastic and Reconstructive Surgery. 14 (5): 305–317. doi:10.1097/00002341-199809000-00002. PMID   9783280. S2CID   13678666.
  50. Waller, R R; Kennedy, R H; Henderson, J W; Kesty, K R (1985). "Management of blepharospasm". Transactions of the American Ophthalmological Society. 83: 367–386. ISSN   0065-9533. PMC   1298706 . PMID   3832534.
  51. Monterastelli, Anna N.; Bailey, Lucy A.; Cockerham, Kimberly (June 2022). "Intense Pulsed Light: A Therapeutic Option for Patients With Rosacea-Related Dry Eye and Blepharospasm". Journal of Neuro-Ophthalmology. 42 (2): e494–e496. doi:10.1097/WNO.0000000000001290. ISSN   1070-8022. PMID   34270518.
  52. Fantato, Alexina; Parulekar, Manoj; Elston, John (2 July 2019). "A trial of a mechanical device for the treatment of blepharospasm". Eye. 33 (11): 1803–1808. doi:10.1038/s41433-019-0495-y. ISSN   0950-222X. PMC   7002569 . PMID   31267089.
  53. Uchida, Kazuko; Kiyosawa, Motohiro; Wakakura, Masato (2020). "Efficacy of a Non-invasive Cosmetic Forcible Trick Treatment for Blepharospasm: Increase in Quality of Life Due to Use of Ultra-thin Adhesive Tape". NeuroOphthalmology Japan. 37 (2): 237–243. doi:10.11476/shinkeiganka.37.237 via JStage.
  54. Farias, J., Sarti-Martínez, MA. Title: "Elite musicians treated by specific fingers motion program to stimulate propiceptive sense", Congreso Nacional De La Sociedad Anatómica Española, Alicante (España), European Journal of Anatomy, p. 110