nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2021-1-119-125nnp-1521Research ArticleREVIEWSОБЗОРЫBenign essential blepharospasm: epidemiology, clinical manifestations, pathophysiology, botulinum toxin therapyДоброкачественный эссенциальный блефароспазм: эпидемиология, клинические проявления, патофизиология, ботулинотерапияЗаляловаЗ. А.ZalyalovaZ. A.

Зулейха Абдуллазяновна Залялова

Кафедра неврологии и реабилитации420012, Казань, ул. Бутлерова, 49

 

Zuleikha Abdullazyanovna Zalyalova

Department of Neurology and Rehabilitation49, Butlerov St., Kazan 420012

 

z.zalyalova@gmail.comФГБОУ ВО «Казанский государственный медицинский университет» Минздрава России; Республиканский консультативно-диагностический центр экстрапирамидной патологии и ботулинотерапии Минздрава Республики ТатарстанРоссияKazan State Medical University, Ministry of Health of Russia; Republican Consultative and Diagnostic Center for Extrapyramidal Pathology and Botulinum Toxin Therapy, Ministry of Health of the Republic of TatarstanRussian Federation202118022021131119125Copyright © Zalyalova Z.A., 20212021Залялова З.А.Zalyalova Z.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/1521

Blepharospasm (BPS) is a variant of focal dystonia manifested by involuntary eyelid spasms with eye closure and/or increased spontaneous blinking. Along with motor symptoms, this condition is characterized by sensory, affective, and cognitive disorders. Patients with BPS are found to have changes in the basal ganglia, cerebellum, primary/secondary sensorimotor and visual areas according to functional magnetic resonance imaging. This may reflect the involvement of above regions in suppressing defective movement and sensorimotor disintegration. Botulinum toxin therapy is the most effective treatment for BPS. The advantage of Xeomin® that does not contain complexing proteins, is characterized by a low probability of antibody production, is the ability to vary between-injection intervals. Probably, botulinum toxin therapy has a pathogenetic and modifying impact on BPS.

Блефароспазм (БФС) – вариант фокальной дистонии, проявляющийся непроизвольным спазмом век с закрыванием глаз и/или c усиленным самопроизвольным морганием. Наряду с двигательными симптомами это состояние характеризуется сенсорными, аффективными и когнитивными нарушениями. У пациентов с БФС выявляются изменения в базальных ганглиях, мозжечке, первичных/вторичных сенсомоторных и визуальных зонах по данным функциональной магнитно-резонансной томографии. Это может отражать вовлечение указанных областей в подавление дефектного движения и сенсомоторной дезинтеграции. Ботулинотерапия – наиболее эффективный метод лечения БФС. Преимуществом Ксеомина®, который не содержит комплексообразующих белков и характеризуется низкой вероятностью образования антител, является возможность варьировать интервалы между инъекциями. Вероятно, ботулинотерапия оказывает патогенетическое и модифицирующее действие на БФС.

дистонияблефароспазмкорригирующий жестапраксия поднимания векафотофобиякруговая мыщца глазасенсомоторная дезинтеграциямигательный рефлексфункциональная магнитно-резонансная томографияботулинотерпияIncobotulinumtoxin Adystoniablepharospasmsensor trickseyelid opening apraxiaphotophobiamusculus orbicularis oculisensorimotor disintegrationwink reflexfunctional magnetic resonance imagingbotulinum toxin therapyIncobotulinotoxin AСтатья спонсируется компанией Мerz.This article has been supported by Merz.ReferencesMarsden CD. Blepharospasm-oromandibular dystonia syndrome (Brueghel’s syndrome). A variant of adult-onset torsion dystonia? J Neurol Neurosurg Psychiatry. 1976;39:1204-9. doi: 10.1136/jnnp.39.12.1204Marsden CD. Blepharospasm-oromandibular dystonia syndrome (Brueghel’s syndrome). A variant of adult-onset torsion dystonia? J Neurol Neurosurg Psychiatry. 1976;39:1204-9. doi: 10.1136/jnnp.39.12.1204Digre KB. Benign essential blepharospasm – there is more to it than just blinking. J Neuroophthalmol. 2015 Dec;35(4):379-81. doi: 10.1097/wno.0000000000000316Digre KB. Benign essential blepharospasm – there is more to it than just blinking. J Neuroophthalmol. 2015 Dec;35(4):379-81. doi: 10.1097/wno.0000000000000316Хаятова ЗГ, Залялова ЗА. Исторические аспекты изучения краниоцервикальной дистонии. Анналы клинической и экспериментальной неврологии. 2019;13(4):91-6. doi: 10.25692/ACEN.2019.4.12Khayatova ZG, Zalyalova ZA. Historical aspects of studying craniocervical dystonia. Annaly klinicheskoy i eksperimental'noy nevrologii = Annals of Clinical and Experimental Neurology. 2019;13(4):91-6. doi: 10.25692/ACEN.2019.4.12 (In Russ.).Henderson JW. Essential blepharospasm. Trans Am Ophthalmol Soc. 1956;54:453-520.Henderson JW. Essential blepharospasm. Trans Am Ophthalmol Soc. 1956;54:453-520.Defazio G, Hallett M, Jinnah HA, et al. Blepharospasm 40 years later. Mov Disord. 2017 Apr;32(4):498-509. doi: 10.1002/mds.26934. Epub 2017 Feb 10.Defazio G, Hallett M, Jinnah HA, et al. Blepharospasm 40 years later. Mov Disord. 2017 Apr;32(4):498-509. doi: 10.1002/mds.26934. Epub 2017 Feb 10.Defazio G, Martino D, Aniello MS, et al. A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):252-4. doi: 10.1136/jnnp.2005.068007Defazio G, Martino D, Aniello MS, et al. A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):252-4. doi: 10.1136/jnnp.2005.068007Defazio G, Abbruzzese G, Livrea P, Berardelli A. Epidemiology of primary dystonia. Lancet Neurol. 2004 Nov;3(11):673-8. doi: 10.1016/S1474-4422(04)00907-XDefazio G, Abbruzzese G, Livrea P, Berardelli A. Epidemiology of primary dystonia. Lancet Neurol. 2004 Nov;3(11):673-8. doi: 10.1016/S1474-4422(04)00907-XSteeves TD, Day L, Dykeman J, et al. The prevalence of primary dystonia: a systematic review and meta-analysis. Mov Disord. 2012 Dec;27(14):1789-96. doi: 10.1002/mds.25244. Epub 2012 Oct 31.Steeves TD, Day L, Dykeman J, et al. The prevalence of primary dystonia: a systematic review and meta-analysis. Mov Disord. 2012 Dec;27(14):1789-96. doi: 10.1002/mds.25244. Epub 2012 Oct 31.Peckham EL, Lopez G, Shamim EA, et al. Clinical features of patients with blepharospasm: a report of 240 patients. Eur J Neurol. 2011 Mar;18(3):382-6. doi: 10.1111/j.1468-1331.2010.03161.xPeckham EL, Lopez G, Shamim EA, et al. Clinical features of patients with blepharospasm: a report of 240 patients. Eur J Neurol. 2011 Mar;18(3):382-6. doi: 10.1111/j.1468-1331.2010.03161.xHallett M, Evinger C, Jankovic J, Stacy M; BEBRF International Workshop. Update on blepharospasm: report from the BEBRF International Workshop. Neurology. 2008 Oct 14;71(16):1275-82. doi: 10.1212/01.wnl.0000327601.46315.85Hallett M, Evinger C, Jankovic J, Stacy M; BEBRF International Workshop. Update on blepharospasm: report from the BEBRF International Workshop. Neurology. 2008 Oct 14;71(16):1275-82. doi: 10.1212/01.wnl.0000327601.46315.85Defazio G, Hallett M, Jinnah HA, et al. Development and validation of a clinical guideline for diagnosing blepharospasm. Neurology. 2013 Jul 16;81(3):236-40. doi: 10.1212/WNL.0b013e31829bfdf6. Epub 2013 Jun 14.Defazio G, Hallett M, Jinnah HA, et al. Development and validation of a clinical guideline for diagnosing blepharospasm. Neurology. 2013 Jul 16;81(3):236-40. doi: 10.1212/WNL.0b013e31829bfdf6. Epub 2013 Jun 14.Abbruzzese G, Berardelli A, Girlanda P, et al. Long-term assessment of the risk of spread in primary late-onset focal dystonia. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):392-6. doi: 10.1136/jnnp.2007.124594. Epub 2007 Jul 17.Abbruzzese G, Berardelli A, Girlanda P, et al. Long-term assessment of the risk of spread in primary late-onset focal dystonia. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):392-6. doi: 10.1136/jnnp.2007.124594. Epub 2007 Jul 17.Defazio G, Conte A, Gigante AF, et al. Is tremor in dystonia a phenotypic feature of dystonia? Neurology. 2015 Mar 10;84(10):1053-9. doi: 10.1212/WNL.0000000000001341. Epub 2015 Feb 6.Defazio G, Conte A, Gigante AF, et al. Is tremor in dystonia a phenotypic feature of dystonia? Neurology. 2015 Mar 10;84(10):1053-9. doi: 10.1212/WNL.0000000000001341. Epub 2015 Feb 6.Weiss EM, Hershey T, Karimi M, et al. Relative risk of spread of symptoms among the focal onset primary dystonias. Movement Disord. 2006 Aug;21(8):1175-81. doi: 10.1002/mds.20919Weiss EM, Hershey T, Karimi M, et al. Relative risk of spread of symptoms among the focal onset primary dystonias. Movement Disord. 2006 Aug;21(8):1175-81. doi: 10.1002/mds.20919Залялова ЗА. Синдром Мейжа или сегментарная краниоцервикальная дистония: терминология, история изучения и современный взгляд. Журнал неврологии и психиатрии им. С.С. Корсакова. 2015;12:133-6. doi: 10.17116/jnevro2015115112133-136Zalyalova ZA. Meige's syndrome or segmental craniocervical dystonia: terminology, history and contemporary view. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2015;115(12):133-6. doi: 10.17116/jnevro2015115112133-136 (In Russ.).Jankovic J, Orman J. Blepharospasm: demographic and clinical survey of 250 patients. Ann Ophthalmol. 1984 Apr;16(4):371-6.Jankovic J, Orman J. Blepharospasm: demographic and clinical survey of 250 patients. Ann Ophthalmol. 1984 Apr;16(4):371-6.Martino D, Defazio G, Abbruzzese G, et al. Head trauma in primary cranial dystonias: a multicentre case-control study [published correction appears in: J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):440. Majorana, Giuseppe [corrected to Majorana, Giovanni]]. J Neurol Neurosurg Psychiatry. 2007 Mar;78(3):260-3. doi: 10.1136/jnnp.2006.103713. Epub 2006 Oct 20.Martino D, Defazio G, Abbruzzese G, et al. Head trauma in primary cranial dystonias: a multicentre case-control study [published correction appears in: J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):440. Majorana, Giuseppe [corrected to Majorana, Giovanni]]. J Neurol Neurosurg Psychiatry. 2007 Mar;78(3):260-3. doi: 10.1136/jnnp.2006.103713. Epub 2006 Oct 20.Defazio G, Livrea P. Epidemiology of primary blepharospasm. Mov Disord. 2002 Jan;17(1):7-12. doi: 10.1002/mds.1275Defazio G, Livrea P. Epidemiology of primary blepharospasm. Mov Disord. 2002 Jan;17(1):7-12. doi: 10.1002/mds.1275Grandas F, Elston J, Quinn N, Marsden CD. Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):767-72. doi: 10.1136/jnnp.51.6.767Grandas F, Elston J, Quinn N, Marsden CD. Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):767-72. doi: 10.1136/jnnp.51.6.767Lamberti P, De Mari M, Zenzola A, et al. Frequency of apraxia of eyelid opening in the general population and in patients with extrapyramidal disorders. Neurol Sci. 2002 Sep;23 Suppl 2:S81-2. doi: 10.1007/s100720200080Lamberti P, De Mari M, Zenzola A, et al. Frequency of apraxia of eyelid opening in the general population and in patients with extrapyramidal disorders. Neurol Sci. 2002 Sep;23 Suppl 2:S81-2. doi: 10.1007/s100720200080Лихачев СА, Аленикова ОА. Двигательная функция век: анатомо-физиологические основы и клиническое значение. Неврологический журнал. 2012;(1):4-9.Likhachev SA, Alenikova OA. The motor function of eyelids: the anatomic and physiological foundations and clinical relevance. Nevrologicheskiy zhurnal = Journal of Neurology. 2012;(1):4-9 (In Russ.).Albanese A. The clinical expression of primary dystonia. J Neurol. 2003;250(10):1145-51. doi: 10.1007/s00415-003-0236-8Albanese A. The clinical expression of primary dystonia. J Neurol. 2003;250(10):1145-51. doi: 10.1007/s00415-003-0236-8Залялова ЗА. Современные классификации мышечных дистоний, стратегия лечения. Журнал неврологии и психиатрии им. С.С. Корсакова. 2013;13:85-9.Zaljalova ZA. Modern classifications of muscular dystonia, treatment strategy. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2013;13:85-9 (In Russ.).Loyola DP, Camargos S, Maia D, et al. Sensory tricks in focal dystonia and hemifacial spasm. Eur J Neurol. 2013 Apr;20(4):704-7. doi: 10.1111/ene.12054. Epub 2012 Dec 7.Loyola DP, Camargos S, Maia D, et al. Sensory tricks in focal dystonia and hemifacial spasm. Eur J Neurol. 2013 Apr;20(4):704-7. doi: 10.1111/ene.12054. Epub 2012 Dec 7.Lorenzano D, Tansley S, Ezra DG. Sensory Trick Frames: A New Device for Blepharospasm Patients. J Mov Disord. 2019 Jan;12(1):22-6. doi: 10.14802/jmd.18010. Epub 2019 Jan 16.Lorenzano D, Tansley S, Ezra DG. Sensory Trick Frames: A New Device for Blepharospasm Patients. J Mov Disord. 2019 Jan;12(1):22-6. doi: 10.14802/jmd.18010. Epub 2019 Jan 16.Martino D, Liuzzi D, Macerollo A, et al. The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia. Movement Disord. 2010 Mar;25(4):407-12. doi: 10.1002/mds.23011Martino D, Liuzzi D, Macerollo A, et al. The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia. Movement Disord. 2010 Mar;25(4):407-12. doi: 10.1002/mds.23011Digre KB, Brennan KC. Shedding light on photophobia. J Neuroophthalmol. 2012;32(1):68-81. doi: 10.1097/WNO.0b013e3182474548Digre KB, Brennan KC. Shedding light on photophobia. J Neuroophthalmol. 2012;32(1):68-81. doi: 10.1097/WNO.0b013e3182474548Adams WH, Digre KB, Patel BC, et al. The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol. 2006;142(1):82-7. doi: 10.1016/j.ajo.2006.02.020Adams WH, Digre KB, Patel BC, et al. The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol. 2006;142(1):82-7. doi: 10.1016/j.ajo.2006.02.020Judd RA, Digre KB, Warner JE, et al. Shedding Light on Blepharospasm: A Patient–Researcher Partnership Approach to Assessment of Photophobia and Impact on Activities of Daily Living. NeuroOphthalmology. 2007;31(3):49-54. doi: 10.1080/01658100701247646Judd RA, Digre KB, Warner JE, et al. Shedding Light on Blepharospasm: A Patient–Researcher Partnership Approach to Assessment of Photophobia and Impact on Activities of Daily Living. NeuroOphthalmology. 2007;31(3):49-54. doi: 10.1080/01658100701247646Okamoto K, Thompson R, Tashiro A, et al. Bright light produces Fos-positive neurons in caudal trigeminal brainstem. Neuroscience. 2009;160(4):858-64. doi: 10.1016/j.neuroscience.2009.03.003Okamoto K, Thompson R, Tashiro A, et al. Bright light produces Fos-positive neurons in caudal trigeminal brainstem. Neuroscience. 2009;160(4):858-64. doi: 10.1016/j.neuroscience.2009.03.003Wu Y, Hallett M. Photophobia in neurologic disorders. Transl Neurodegener. 2017 Sep 20;6:26. doi: 10.1186/s40035-017-0095-3. eCollection 2017.Wu Y, Hallett M. Photophobia in neurologic disorders. Transl Neurodegener. 2017 Sep 20;6:26. doi: 10.1186/s40035-017-0095-3. eCollection 2017.Noseda R, Constandil L, Bourgeais L, et al. Changes of meningeal excitability mediated by corticotrigeminal networks: a link for the endogenous modulation of migraine pain. J Neurosci. 2010 Oct 27;30(43):14420-9. doi: 10.1523/JNEUROSCI.3025-10.2010Noseda R, Constandil L, Bourgeais L, et al. Changes of meningeal excitability mediated by corticotrigeminal networks: a link for the endogenous modulation of migraine pain. J Neurosci. 2010 Oct 27;30(43):14420-9. doi: 10.1523/JNEUROSCI.3025-10.2010Dolgonos S, Ayyala H, Evinger C. Lightinduced trigeminal sensitization without central visual pathways: another mechanism for photophobia. Invest Ophthalmol Vis Sci. 2011;52(11):7852-8. doi: 10.1167/iovs.11-7604Dolgonos S, Ayyala H, Evinger C. Lightinduced trigeminal sensitization without central visual pathways: another mechanism for photophobia. Invest Ophthalmol Vis Sci. 2011;52(11):7852-8. doi: 10.1167/iovs.11-7604Xue T, Do MT, Riccio A, et al. Melanopsin signalling in mammalian iris and retina.Nature. 2011;479(7371):67-73. doi:10.1038/nature10567. Epub 2011 Nov 2.Xue T, Do MT, Riccio A, et al. Melanopsin signalling in mammalian iris and retina.Nature. 2011;479(7371):67-73. doi:10.1038/nature10567. Epub 2011 Nov 2.Чернуха ТН, Лихачев СА, Навоша СА. Орофациальные двигательные расстройства: подходы к диагностике и лечению. Медицинские новости. 2016;1(256):9-12.Chernuha TN, Lihachev SA, Navosha SA. Orofacial movement disorders: approaches to diagnosis and treatment. Meditsinskie novosti. 2016;1(256):9-12 (In Russ.).Артеменко АР, Шавловская ОА, Мхитарян ЭР. Актуальные вопросы применения ботулинического токсина типа А при лечении блефароспазма. Клиницист. 2019;13(3-4):43-52. doi: 10.17650/1818-8338-2019-13-34-43-52Artemenko AR, Shavlovskaya OA, Mkhitaryan ER. Specificity of using botulinic toxin type A for blepharospasm treatment. Klinitsist = The Clinician. 2019;13(3-4):43-52. doi: 10.17650/1818-8338-2019-13-3-4-43-52 (In Russ.).Peller M, Zeuner KE, Munchau A, et al. The basal ganglia are hyperactive during the discrimination of tactile stimuli in writer's cramp. Brain. 2006 Oct;129(Pt 10):2697-708. doi: 10.1093/brain/awl181. Epub 2006 Jul 19.Peller M, Zeuner KE, Munchau A, et al. The basal ganglia are hyperactive during the discrimination of tactile stimuli in writer's cramp. Brain. 2006 Oct;129(Pt 10):2697-708. doi: 10.1093/brain/awl181. Epub 2006 Jul 19.Evinger C. Benign Essential blepharospasm is a disorder of neuroplasticity: lessons from animal models. J Neuroophthalmol. 2015 Dec;35(4):374-9. doi: 10.1097/WNO.0000000000000317Evinger C. Benign Essential blepharospasm is a disorder of neuroplasticity: lessons from animal models. J Neuroophthalmol. 2015 Dec;35(4):374-9. doi: 10.1097/WNO.0000000000000317Osaki MH, Osaki TH, Garcia DM, et al. Analysis of blink activity and anomalous eyelid movements in patients with hemifacial spasm. Graefes Arch Clin Exp Ophthalmol. 2020 Mar;258(3):669-74. doi: 10.1007/s00417-01904567-w. Epub 2019 Dec 20.Osaki MH, Osaki TH, Garcia DM, et al. Analysis of blink activity and anomalous eyelid movements in patients with hemifacial spasm. Graefes Arch Clin Exp Ophthalmol. 2020 Mar;258(3):669-74. doi: 10.1007/s00417-01904567-w. Epub 2019 Dec 20.Basso MA, Evinger C. An explanation for reflex blink hyperexcitability in Parkinson's disease. II. Nucleus raphe magnus. J Neurosci. 1996 Nov 15;16(22):7318-30. doi: 10.1523/JNEUROSCI.16-22-07318.1996Basso MA, Evinger C. An explanation for reflex blink hyperexcitability in Parkinson's disease. II. Nucleus raphe magnus. J Neurosci. 1996 Nov 15;16(22):7318-30. doi: 10.1523/JNEUROSCI.16-22-07318.1996Gomez-Wong E, Marti MJ, Tolosa E, et al. Sensory modulation of the blink reflex in patients with blepharospasm. Arch Neurol. 1998 Sep;55(9):1233-7. doi: 10.1001/archneur.55.9.1233Gomez-Wong E, Marti MJ, Tolosa E, et al. Sensory modulation of the blink reflex in patients with blepharospasm. Arch Neurol. 1998 Sep;55(9):1233-7. doi: 10.1001/archneur.55.9.1233Conte A, Defazio G, Ferrazzano G, et al. Is increased blinking a form of blepharospasm? Neurology. 2013 Jun 11;80(24):2236-41. doi: 10.1212/WNL.0b013e318296e99dConte A, Defazio G, Ferrazzano G, et al. Is increased blinking a form of blepharospasm? Neurology. 2013 Jun 11;80(24):2236-41. doi: 10.1212/WNL.0b013e318296e99dPauletti G, Berardelli A, Cruccu G, et al. Blink reflex and the masseter inhibitory reflex in patients with dystonia. Mov Disord. 1993 Oct;8(4):495-500. doi: 10.1002/mds.870080414Pauletti G, Berardelli A, Cruccu G, et al. Blink reflex and the masseter inhibitory reflex in patients with dystonia. Mov Disord. 1993 Oct;8(4):495-500. doi: 10.1002/mds.870080414Defazio G, Berardelli A, Hallett M. Do primary adult-onset focal dystonias share aetiological factors? Brain. 2007;130(Pt 5):1183-93. doi: 10.1093/brain/awl355Defazio G, Berardelli A, Hallett M. Do primary adult-onset focal dystonias share aetiological factors? Brain. 2007;130(Pt 5):1183-93. doi: 10.1093/brain/awl355Katz BJ, Digre KB. Diagnosis, pathophysiology, and treatment of photophobia. Surv Ophthalmol. Jul-Aug 2016;61(4):466-77. doi: 10.1016/j.survophthal.2016.02.001. Epub 2016 Feb 12.Katz BJ, Digre KB. Diagnosis, pathophysiology, and treatment of photophobia. Surv Ophthalmol. Jul-Aug 2016;61(4):466-77. doi: 10.1016/j.survophthal.2016.02.001. Epub 2016 Feb 12.Williams DT, Ford B, Fahn S. Phenomenology and psychopathology related to psychogenic movement disorders. Adv Neurol. 1995;65:231-57.Williams DT, Ford B, Fahn S. Phenomenology and psychopathology related to psychogenic movement disorders. Adv Neurol. 1995;65:231-57.Schwingenschuh P, Katschnig P, Edwards MJ, et al. The blink reflex recovery cycle differs between essential and presumed psychogenic blepharospasm. Neurology. 2011;76(7):610-4. doi: 10.1212/WNL.0b013e31820c3074Schwingenschuh P, Katschnig P, Edwards MJ, et al. The blink reflex recovery cycle differs between essential and presumed psychogenic blepharospasm. Neurology. 2011;76(7):610-4. doi: 10.1212/WNL.0b013e31820c3074Espay AJ, Morgante F, Purzner J, et al. Cortical and spinal abnormalities in psychogenic dystonia. Ann Neurol. 2006 May;59(5):825-34. doi: 10.1002/ana.20837Espay AJ, Morgante F, Purzner J, et al. Cortical and spinal abnormalities in psychogenic dystonia. Ann Neurol. 2006 May;59(5):825-34. doi: 10.1002/ana.20837Sohn YH, Voller B, Dimyan M, et al. Cortical control of voluntary blinking: a transcranial magnetic stimulation study. Clin Neurophysiol. 2004 Feb;115(2):341-7. doi: 10.1016/j.clinph.2003.10.035Sohn YH, Voller B, Dimyan M, et al. Cortical control of voluntary blinking: a transcranial magnetic stimulation study. Clin Neurophysiol. 2004 Feb;115(2):341-7. doi: 10.1016/j.clinph.2003.10.035Horovitz S, Ford A, Najee-Ullah M, et al. Anatomical correlates of blepharospasm. Transl Neurodegener. 2012 Jun 15;1(1):12. doi: 10.1186/2047-9158-1-12Horovitz S, Ford A, Najee-Ullah M, et al. Anatomical correlates of blepharospasm. Transl Neurodegener. 2012 Jun 15;1(1):12. doi: 10.1186/2047-9158-1-12Wolpe N, Moore JW, Rae CL, et al. The medial frontal-prefrontal network for altered awareness and control of action in corticobasal syndrome. Brain. 2014 Jan;137(Pt 1):208-20. doi: 10.1093/brain/awt302. Epub 2013 Nov 29.Wolpe N, Moore JW, Rae CL, et al. The medial frontal-prefrontal network for altered awareness and control of action in corticobasal syndrome. Brain. 2014 Jan;137(Pt 1):208-20. doi: 10.1093/brain/awt302. Epub 2013 Nov 29.Nachev P, Kennard C, Husain M. Functional role of the supplementary and presupplementary motorareas. Nat Rev Neurosci. 2008 Nov;9(11):856-69. doi: 10.1038/nrn2478. Epub 2008 Oct 9.Nachev P, Kennard C, Husain M. Functional role of the supplementary and presupplementary motorareas. Nat Rev Neurosci. 2008 Nov;9(11):856-69. doi: 10.1038/nrn2478. Epub 2008 Oct 9.Morcuende S, Delgado-Garcia JM, Ugolini G. Neuronal premotor networks involved in eyelid responses: retrograde transneuronal tracing with rabies virus from the orbicularis oculi muscle in the rat. J Neurosci. 2002;22(20):8808-18. doi: 10.1523/JNEUROSCI.22-20-08808.2002Morcuende S, Delgado-Garcia JM, Ugolini G. Neuronal premotor networks involved in eyelid responses: retrograde transneuronal tracing with rabies virus from the orbicularis oculi muscle in the rat. J Neurosci. 2002;22(20):8808-18. doi: 10.1523/JNEUROSCI.22-20-08808.2002Kaji R, Bhatia K, Graybiel AM. Pathogenesis of dystonia: is it of cerebellar or basal ganglia origin? J Neurol Neurosurg Psychiatry. 2018 May;89(5):488-92. doi: 10.1136/jnnp-2017-316250. Epub 2017 Oct 31.Kaji R, Bhatia K, Graybiel AM. Pathogenesis of dystonia: is it of cerebellar or basal ganglia origin? J Neurol Neurosurg Psychiatry. 2018 May;89(5):488-92. doi: 10.1136/jnnp-2017-316250. Epub 2017 Oct 31.Tournier JD, Mori S, Leemans A. Diffusion tensor imaging and beyond. Magn Reson Med. 2011 Jun;65(6):1532-56. doi: 10.1002/mrm.22924. Epub 2011 Apr 5.Tournier JD, Mori S, Leemans A. Diffusion tensor imaging and beyond. Magn Reson Med. 2011 Jun;65(6):1532-56. doi: 10.1002/mrm.22924. Epub 2011 Apr 5.Quartarone A, Pisani A. Abnormal plasticity in dystonia: Disruption of synaptic homeostasis. Neurobiol Dis. 2011 May;42(2):162-70. doi: 10.1016/j.nbd.2010.12.011. Epub 2010 Dec 16.Quartarone A, Pisani A. Abnormal plasticity in dystonia: Disruption of synaptic homeostasis. Neurobiol Dis. 2011 May;42(2):162-70. doi: 10.1016/j.nbd.2010.12.011. Epub 2010 Dec 16.Codazzi F, Pelizzoni I, Zacchetti D, et al. Iron entry in neurons and astrocytes: a link with synaptic activity. Front Mol Neurosci. 2015;8:18. doi: 10.3389/fnmol.2015.00018. Epub 2015 Jun 3.Codazzi F, Pelizzoni I, Zacchetti D, et al. Iron entry in neurons and astrocytes: a link with synaptic activity. Front Mol Neurosci. 2015;8:18. doi: 10.3389/fnmol.2015.00018. Epub 2015 Jun 3.Murai H, Suzuki Y, Kiyosawa M, et al. Positive correlation between severity of blepharospasm and thalamic glucose metabolism. Case Rep Ophthalmol. 2011 Jan;2(1):50-4. doi: 10.1159/000324459. Epub 2011 Feb 5.Murai H, Suzuki Y, Kiyosawa M, et al. Positive correlation between severity of blepharospasm and thalamic glucose metabolism. Case Rep Ophthalmol. 2011 Jan;2(1):50-4. doi: 10.1159/000324459. Epub 2011 Feb 5.Anderson RL, Patel BC, Holds JB, Jordan DR. Blepharospasm: past, present, and future. Ophthalm Plast Reconstr Surg. 1998 Sep;14(5):305-17.Anderson RL, Patel BC, Holds JB, Jordan DR. Blepharospasm: past, present, and future. Ophthalm Plast Reconstr Surg. 1998 Sep;14(5):305-17.Aramideh M, Ongerboer de Visser BW, Brans JW, et al. Pretarsal application of botulinum toxin for treatment of blepharospasm. J Neurol Neurosurg Psychiatry. 1995;59(3):309-11. doi: 10.1136/jnnp.59.3.309Aramideh M, Ongerboer de Visser BW, Brans JW, et al. Pretarsal application of botulinum toxin for treatment of blepharospasm. J Neurol Neurosurg Psychiatry. 1995;59(3):309-11. doi: 10.1136/jnnp.59.3.309Albanese A, Bentivoglio AR, Colosimo C, et al. Pretarsal injections of botulinum toxin improve blepharospasm in previously unresponsive patients. J Neurol Neurosurg Psychiatry. 1996;60(6):693-4. doi:10.1136/jnnp.60.6.693-aAlbanese A, Bentivoglio AR, Colosimo C, et al. Pretarsal injections of botulinum toxin improve blepharospasm in previously unresponsive patients. J Neurol Neurosurg Psychiatry. 1996;60(6):693-4. doi:10.1136/jnnp.60.6.693-aKenney C, Jankovic J. Botulinum toxin in the treatment of blepharospasm and hemifacial spasm. J Neural Transm (Vienna). 2008;115(4):585-91. doi: 10.1007/s00702-0070768-7. Epub 2007 Jun 11.Kenney C, Jankovic J. Botulinum toxin in the treatment of blepharospasm and hemifacial spasm. J Neural Transm (Vienna). 2008;115(4):585-91. doi: 10.1007/s00702-0070768-7. Epub 2007 Jun 11.Ozzello DJ, Giacometti JN. Botulinum toxins for treating essential blepharospasm and hemifacial spasm. Int Ophthalmol Clin. 2018;58(1):49-61. doi:10.1097/IIO.0000000000000203Ozzello DJ, Giacometti JN. Botulinum toxins for treating essential blepharospasm and hemifacial spasm. Int Ophthalmol Clin. 2018;58(1):49-61. doi:10.1097/IIO.0000000000000203Pagan FL, Harrison A. A guide to dosing in the treatment of cervical dystonia and blepharospasm with Xeomin® : a new botulinum neurotoxin A. Parkinsonism Relat Disord. 2012;18(5):441-5. doi: 10.1016/j.parkreldis.2012.02.008Pagan FL, Harrison A. A guide to dosing in the treatment of cervical dystonia and blepharospasm with Xeomin® : a new botulinum neurotoxin A. Parkinsonism Relat Disord. 2012;18(5):441-5. doi: 10.1016/j.parkreldis.2012.02.008Dressler D. Five-year experience with incobotulinumtoxin A (Xeomin): the first botulinum toxin drug free of complexing proteins. Eur J Neurol. 2012;19(3):385-9. doi: 10.1111/j.1468-1331.2011.03559.xDressler D. Five-year experience with incobotulinumtoxin A (Xeomin): the first botulinum toxin drug free of complexing proteins. Eur J Neurol. 2012;19(3):385-9. doi: 10.1111/j.1468-1331.2011.03559.xTruong DD, Gollomp SM, Jankovic J, et al. Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin( ® )) injections in blepharospasm. J Neural Transm (Vienna). 2013;120(9):1345-53. doi: 10.1007/s00702-0130998-9Truong DD, Gollomp SM, Jankovic J, et al. Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin( ® )) injections in blepharospasm. J Neural Transm (Vienna). 2013;120(9):1345-53. doi: 10.1007/s00702-0130998-9Wabbels B, Roggenkämper P. Essenzieller Blepharospasmus: Praxisnahe Therapie mit Botulinumtoxin unter Verwendung verkürzter Behandlungsintervalle [Essential blepharospasm: Practice-oriented therapy with botulinum toxin employing reduced treatment intervals]. Ophthalmologe. 2012;109(1):45-53. doi: 10.1007/s00347-011-2457-zWabbels B, Roggenkämper P. Essenzieller Blepharospasmus: Praxisnahe Therapie mit Botulinumtoxin unter Verwendung verkürzter Behandlungsintervalle [Essential blepharospasm: Practice-oriented therapy with botulinum toxin employing reduced treatment intervals]. Ophthalmologe. 2012;109(1):45-53. doi: 10.1007/s00347-011-2457-zHallett M, Albanese A, Dressler D, et al. Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders. Toxicon. 2013 Jun 1;67:94-114. doi: 10.1016/j.toxicon.2012.12.004. Epub 2013 Feb 4.Hallett M, Albanese A, Dressler D, et al. Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders. Toxicon. 2013 Jun 1;67:94-114. doi: 10.1016/j.toxicon.2012.12.004. Epub 2013 Feb 4.Jost WH, Benecke R, Hauschke D, et al. Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders. Drug Des Devel Ther. 2015 Apr 1;9:1913-26. doi: 10.2147/DDDT.S79193. eCollection 2015.Jost WH, Benecke R, Hauschke D, et al. Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders. Drug Des Devel Ther. 2015 Apr 1;9:1913-26. doi: 10.2147/DDDT.S79193. eCollection 2015.Quartarone A, Sant'Angelo A, Battaglia F, et al. Enhanced long-term potentiation-like plasticity of the trigeminal blink reflex circuit in blepharospasm. J Neurosci. 2006 Jan 11;26(2):716-21. doi: 10.1523/JNEUROSCI.3948-05.2006Quartarone A, Sant'Angelo A, Battaglia F, et al. Enhanced long-term potentiation-like plasticity of the trigeminal blink reflex circuit in blepharospasm. J Neurosci. 2006 Jan 11;26(2):716-21. doi: 10.1523/JNEUROSCI.3948-05.2006Dresel C, Bayer F, Castrop F, et al. Botulinum toxin modulates basal ganglia but not deficient somatosensory activation in orofacial dystonia. Mov Disord. 2011 Jul;26(8):1496-502. doi: 10.1002/mds.23497. Epub 2011 May 20.Dresel C, Bayer F, Castrop F, et al. Botulinum toxin modulates basal ganglia but not deficient somatosensory activation in orofacial dystonia. Mov Disord. 2011 Jul;26(8):1496-502. doi: 10.1002/mds.23497. Epub 2011 May 20.Alexandru H, Muthuraman M, Chirumamilla VC, et al. Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy [published correction appears in: PLoS One. 2017 Feb 13;12(2):e0172374]. PLoS One. 2016 Dec 16;11(12):e0168652. doi: 10.1371/journal.pone.0168652. eCollection 2016.Alexandru H, Muthuraman M, Chirumamilla VC, et al. Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy [published correction appears in: PLoS One. 2017 Feb 13;12(2):e0172374]. PLoS One. 2016 Dec 16;11(12):e0168652. doi: 10.1371/journal.pone.0168652. eCollection 2016.

The authors declare that there are no conflicts of interest present.