Blepharospasm – from diagnosis to proper treatment
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Published:
Mar 31, 2019
Keywords:
blepharospasm, treatment, botulinum toxin, diagnosis
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Abstract
Background: Blepharospasm is a movement disorder characterized by involuntary spasms of eye-closing muscles. This second most common adult-onset focal dystonia still raises many doubts among ophthalmologists and neurologists.
Aim of the study: To present current knowledge about blepharospasm with historical background of the disease.
Methods: Literature review regarding diagnosis, pathophysiology and treatment of blepharospasm.
Results: Different types of eye-closing spasms, the spread of dystonia, co-occurrence of eyelid opening apraxia, enhanced blinking, sensory trick and psychiatric disorders define blepharospasm as a heterogeneous condition. Actual genetic, electrophysiological and neuroimaging studies reveal complex and multifocal involuntary movements generators defining blepharospasm and other focal dystonias as a ”communication node disorders” where botulinum toxin acting at the end of all pathways is the first-line treatment.
Conclusions: The history of blepharospasm as a neurological condition that affects the eye shows that the most important discoveries regarding the diagnosis, pathophysiology and treatment of this disease have occurred owing to ophthalmologists and neurologists. Therefore, the future of blepharospasm will also depend on this cooperation.
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Schinwelski M. Blepharospasm – from diagnosis to proper treatment. Ophthatherapy [Internet]. 2019Mar.31 [cited 2024Dec.22];6(1):43-0. Available from: https://journalsmededu.pl/index.php/ophthatherapy/article/view/509
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Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
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2. Mackenzie W. Case of intense and long-continued photophobia and blepharospasm relieved by the inhalation of chloroform. Med Chi Trans. 1857; 40: 175-8.
3. Marsden CD. Blepharospasm-oromandibular dystonia syndrome (Brueghel’s syndrome). A variant of adult onset torsion dystonia? J Neurol Neurosurg Psychiatry. 1976; 39: 1204-9.
4. Steeves TD, Day L, Dykeman J et al. The prevalence of primary dystonia: a systematic review and meta analysis. Mov Disord. 2012; 27: 1789-96.
5. Martino D, Livrea P, Giorelli M et al. Menopause and menarche in patients with primary blepharospasm: an exploratory case-control study. Eur Neurol. 2002; 47: 161-4.
6. Conte A, Defazio G, Ferrazzano G et al. Is increased blinking a form of blepharospasm? Neurology. 2013; 80: 2236-41.
7. Lamberti P, De Mari M, Zenzola A et al. Frequency of apraxia of eyelid opening in the general population andbin patients with extrapyramidal disorders. Neurol Sci. 2002; 23(2): S81-2.
8. Defazio G, Livrea P, Lamberti P et al. Isolated So-Called Apraxia of Eyelid Opening: Report of 10 Cases and a Review of the Literature. Eur Neurol. 1998; 39: 204-10.
9. Krack P, Marion MH. “Apraxia of lid opening” a focal eyelid dystonia: clinical study of 32 patients. Mov Disord. 1994; 9: 610-5.
10. Umemura A, Toyoda T, Yamamoto K et al. Apraxia of eyelid opening after subthalamic deep brain stimulation may be caused by reduction of levodopa. Parkinsonism Relat Disord. 2008; 14: 655-7.
11. Weiss D, Wächter T, Breit S et al. Involuntary eyelid closure after STN-DBS: evidence for different pathophysiological entities. J Neurol Neurosurg Psychiatry. 2010; 81: 1002-7.
12. 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; 79: 392-6.
13. Berardelli A, Abbruzzese G, Chen R et al. Consensus paper on short-interval intracortical inhibition and other transcranial magnetic stimulation intracortical paradigms in movement disorders. Brain Stimul. 2008; 1: 183-91.
14. Defazio G, Matarin M, Peckham EL et al. The TOR1A polymorphism rs1182 and the risk of spread in primary blepharospasm. Mov Disord. 2009; 24: 613-6.
15. Adams WH, Digre KB, Patel BC et al. The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol. 2006; 142: 82-7.
16. Blackburn MK, Lamb RD, Digre KB et al. FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm. Ophthalmology. 2009; 116: 997-1001.
17. Grandas F, Elston J, Quinn N et al. Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry. 1988; 51(6): 767-72.
18. Martino D, Liuzzi D, Macerollo A et al. The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia. Mov Disord. 2010; 25: 407-12.
19. Schramm A, Reiners K, Naumann M. Complex mechanisms of sensory tricks in cervical dystonia. Mov Disord. 2004; 19: 452-8.
20. Brissaud E. Vingt-quatrième leçon. Tics et spasmes cloniques de la face. In: Meige H (ed). Leçons sur les maladies nerveuses: La Salpêtrière 1893–1894. Paris: Masson 1895: 502-20.
21. Fabbrini G, Berardelli I, Moretti G et al. Psychiatric disorders in adult-onset focal dystonia: a case-control study. Mov Disord. 2010; 25: 459-65.
22. Broocks A, Thiel A, Angerstein D, Dressler D. Higher prevalence of obsessive-compulsive symptoms in patients with blepharospasm than in patients with hemifacial spasm. Am J Psychiatry. 1998; 155: 555-7.
23. Defazio G, Hallett M, Jinnah HA, Berardelli A. Development and validation of a clinical guideline for diagnosing blepharospasm. Neurology. 2013; 81: 236-40.
24. Albanese A, Sorbo FD, Comella C et al. Dystonia rating scales: critique and recommendations. Mov Disord. 2013; 28: 874-83.
25. Defazio G, Hallett M, Jinnah HA et al. Development and validation of a clinical scale for rating the severity of blepharospasm. Mov Disord. 2015; 30: 525-30.
26. Defazio G, Martino D, Aniello MS et al. A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry. 2006; 77: 252-4.
27. Fuchs T, Saunders-Pullman R, Masuho I et al. Mutations in GNAL cause primary torsion dystonia. Nat Genet. 2013; 45: 88-92.
28. Charlesworth G, Plagnol V, Holmström KM et al. Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis. Am J Hum Genet. 2012; 91: 1041-50.
29. Hersheson J, Mencacci NE, Davis M et al. Mutations in the autoregulatory domain of b-tubulin 4a cause hereditary dystonia. Ann Neurol. 2013; 73: 546-53.
30. Xiao J, Uitti RJ, Zhao Y et al. Mutations in CIZ1 cause adult onset primary cervical dystonia. Ann Neurol. 2012; 71: 458-69.
31. Defazio G, Abbruzzese G, Aniello MS et al. Eye symptoms in relatives of patients with primary adult-onset dystonia. Mov Disord. 2012; 27: 305-57.
32. Defazio G, Martino D, Abbruzzese G et al. Influence of coffee drinking and cigarette smoking on the risk of primary late onset blepharospasm: evidence from a multicentre case control study. J Neurol Neurosurg Psychiatry. 2007; 78: 877-9.
33. Khooshnoodi MA, Factor SA, Jinnah HA. Secondary blepharospasm associated with structural lesions of the brain. J Neurol Sci. 2013; 331: 98-101.
34. Rana AQ, Kabir A, Dogu O et al. Prevalence of blepharospasm and apraxia of eyelid opening in patients with parkinsonism, cervical dystonia and essential tremor. Eur Neurol. 2012; 68: 318-21.
35. Zadori D, Veres G, Szalardy L et al. Druginduced movement disorders. Expert Opin Drug Saf. 2015; 14: 877-90.
36. Valls-Sole J, Montero J. Movement disorders in patients with peripheral facial palsy. Mov Disord. 2003; 18: 1424-35.
37. Berardelli A, Rothwell JC, Day BL, Marsden CD. Pathophysiology of blepharospasm and oromandibular dystonia. Brain. 1985; 108: 593-608.
38. Conte A, Defazio G, Ferrazzano G et al. Is increased blinking a form of blepharospasm? Neurology. 2013; 80: 2236-41.
39. Quartarone A, Morgante F, Sant’angelo A et al. Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia. J Neurol Neurosurg Psychiatry. 2008; 79: 985-90.
40. Feiwell RJ, Black KJ, McGee-Minnich LA et al. Diminished regional cerebral blood flow response to vibration in patients with blepharospasm. Neurology. 1999; 52: 291-7.
41. Dresel C, Haslinger B, Castrop F et al. Silent event-related fMRI reveals deficient motor and enhanced somatosensory activation in orofacial dystonia. Brain. 2006; 129: 36-46.
42. Yang J, Luo C, Song W et al. Diffusion tensor imaging in blepharospasm and blepharospasm-oromandibular dystonia. J Neurol. 2014; 261: 1413-24.
43. Henderson JW. Essential blepharospasm. Trans Am Ophthalmol Soc. 1956; 54: 453-520.
44. Nutt JG, Hammerstad JP, deGarmo P, Carter J. Cranial dystonia: double-blind crossover study of anticholinergics. Neurology. 1984; 34: 215-7.
45. Gurdjian ES, Williams HW. The surgical treatment of intractable blepharospasm. JAMA. 1928; 91: 2053-6.
46. Coleman CC. Surgical treatment of facial spasm. Ann Surg. 1937; 105: 638-57.
47. Greenwood J. The surgical treatment of hemifacial spasm. J Neurosurg. 1946; 3: 506-10.
48. Gillum WN, Anderson RL. Blepharospasm surgery: anatomic approach. Arch Ophthalmol. 1981; 99: 1056-62.
49. Anderson RL, Patel BC, Holds JB et al. Blepharospasm: past, present, and future. Ophthal Plast Reconstr Surg. 1998; 14: 305-7.
50. Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology. 1980; 87: 1044-9.
51. Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol. 1985; 103: 347-50.
52. Simpson DM, Hallett M, Ashman EJ et al. 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. 2016; 86: 1818-26.
53. Bilyk JR, Yen MT, Bradley EA et al. Chemodenervation for the Treatment of Facial Dystonia: A Report by the American Academy of Ophthalmology. Ophthalmology. 2018; 125(9): 1459-67.
54. Pellizzari R, Rossetto O, Schiavo G, Montecucco C. Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses. Philos Trans R Soc Lond B Biol Sci. 1999; 354: 259-68.
55. Dressler D, Pan L, Adib Saberi F. Antibody-induced failure of botulinum toxin therapy: re-start with low-antigenicity drugs offers a new treatment opportunity. J Neural Transm (Vienna). 2018; 125(10): 1481-6.
56. Jost WH, Kohl A. Botulinum toxin: evidence based medicine criteria in blepharospasm and hemifacial spasm. J Neurol. 2001; 248(1): 21-4.
57. Albanese A, Bentivoglio AR, Colosimo C et al. Pretarsal injections of botulinum toxin improve blepharospasm in previously unresponsive patients. J Neurol Neurosurg Psychiatry. 1996; 60: 693-4.
58. Levy RL, Berman D, Parikh M, Miller NR. Supramaximal doses of botulinum toxin for refractory blepharospasm. Ophthalmology. 2006; 113(9): 1665-8.
59. Ochudło S, Bryniarski P, Opala G. Botulinum toxin improves the quality of life and reduces the intensification of depressive symptoms in patients with blepharospasm. Parkinsonism Relat Disord. 2007; 13(8): 505-8.
60. Calace P, Cortese G, Piscopo R et al. Treatment of blepharospasm with botulinum neurotoxin type A: long-term results. Eur J Ophthalmol. 2003; 13(4): 331-6.
61. Dressler D, Karapantzou C, Rohrbach S et al. Frontalis suspension surgery to treat patients with blepharospasm and eyelid opening apraxia: long-term results. J Neural Transm (Vienna). 2017; 124(2): 253-7.
62. Reese R, Gruber D, Schoenecker T et al. Long-term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation. Mov Disord. 2011; 26: 691-8.
63. Lorenzano D, Tansley S, Ezra DG. Sensory Trick Frames: A New Device for Blepharospasm Patients. J Mov Disord. 2019; 12(1): 22-6.
64. Macerollo A, Superbo M, Gigante AF et al. Diagnostic delay in adult-onset dystonia: data from an Italian movement disorder center. J Clin Neurosci. 2015; 22(3): 608-10.
2. Mackenzie W. Case of intense and long-continued photophobia and blepharospasm relieved by the inhalation of chloroform. Med Chi Trans. 1857; 40: 175-8.
3. Marsden CD. Blepharospasm-oromandibular dystonia syndrome (Brueghel’s syndrome). A variant of adult onset torsion dystonia? J Neurol Neurosurg Psychiatry. 1976; 39: 1204-9.
4. Steeves TD, Day L, Dykeman J et al. The prevalence of primary dystonia: a systematic review and meta analysis. Mov Disord. 2012; 27: 1789-96.
5. Martino D, Livrea P, Giorelli M et al. Menopause and menarche in patients with primary blepharospasm: an exploratory case-control study. Eur Neurol. 2002; 47: 161-4.
6. Conte A, Defazio G, Ferrazzano G et al. Is increased blinking a form of blepharospasm? Neurology. 2013; 80: 2236-41.
7. Lamberti P, De Mari M, Zenzola A et al. Frequency of apraxia of eyelid opening in the general population andbin patients with extrapyramidal disorders. Neurol Sci. 2002; 23(2): S81-2.
8. Defazio G, Livrea P, Lamberti P et al. Isolated So-Called Apraxia of Eyelid Opening: Report of 10 Cases and a Review of the Literature. Eur Neurol. 1998; 39: 204-10.
9. Krack P, Marion MH. “Apraxia of lid opening” a focal eyelid dystonia: clinical study of 32 patients. Mov Disord. 1994; 9: 610-5.
10. Umemura A, Toyoda T, Yamamoto K et al. Apraxia of eyelid opening after subthalamic deep brain stimulation may be caused by reduction of levodopa. Parkinsonism Relat Disord. 2008; 14: 655-7.
11. Weiss D, Wächter T, Breit S et al. Involuntary eyelid closure after STN-DBS: evidence for different pathophysiological entities. J Neurol Neurosurg Psychiatry. 2010; 81: 1002-7.
12. 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; 79: 392-6.
13. Berardelli A, Abbruzzese G, Chen R et al. Consensus paper on short-interval intracortical inhibition and other transcranial magnetic stimulation intracortical paradigms in movement disorders. Brain Stimul. 2008; 1: 183-91.
14. Defazio G, Matarin M, Peckham EL et al. The TOR1A polymorphism rs1182 and the risk of spread in primary blepharospasm. Mov Disord. 2009; 24: 613-6.
15. Adams WH, Digre KB, Patel BC et al. The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol. 2006; 142: 82-7.
16. Blackburn MK, Lamb RD, Digre KB et al. FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm. Ophthalmology. 2009; 116: 997-1001.
17. Grandas F, Elston J, Quinn N et al. Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry. 1988; 51(6): 767-72.
18. Martino D, Liuzzi D, Macerollo A et al. The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia. Mov Disord. 2010; 25: 407-12.
19. Schramm A, Reiners K, Naumann M. Complex mechanisms of sensory tricks in cervical dystonia. Mov Disord. 2004; 19: 452-8.
20. Brissaud E. Vingt-quatrième leçon. Tics et spasmes cloniques de la face. In: Meige H (ed). Leçons sur les maladies nerveuses: La Salpêtrière 1893–1894. Paris: Masson 1895: 502-20.
21. Fabbrini G, Berardelli I, Moretti G et al. Psychiatric disorders in adult-onset focal dystonia: a case-control study. Mov Disord. 2010; 25: 459-65.
22. Broocks A, Thiel A, Angerstein D, Dressler D. Higher prevalence of obsessive-compulsive symptoms in patients with blepharospasm than in patients with hemifacial spasm. Am J Psychiatry. 1998; 155: 555-7.
23. Defazio G, Hallett M, Jinnah HA, Berardelli A. Development and validation of a clinical guideline for diagnosing blepharospasm. Neurology. 2013; 81: 236-40.
24. Albanese A, Sorbo FD, Comella C et al. Dystonia rating scales: critique and recommendations. Mov Disord. 2013; 28: 874-83.
25. Defazio G, Hallett M, Jinnah HA et al. Development and validation of a clinical scale for rating the severity of blepharospasm. Mov Disord. 2015; 30: 525-30.
26. Defazio G, Martino D, Aniello MS et al. A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry. 2006; 77: 252-4.
27. Fuchs T, Saunders-Pullman R, Masuho I et al. Mutations in GNAL cause primary torsion dystonia. Nat Genet. 2013; 45: 88-92.
28. Charlesworth G, Plagnol V, Holmström KM et al. Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis. Am J Hum Genet. 2012; 91: 1041-50.
29. Hersheson J, Mencacci NE, Davis M et al. Mutations in the autoregulatory domain of b-tubulin 4a cause hereditary dystonia. Ann Neurol. 2013; 73: 546-53.
30. Xiao J, Uitti RJ, Zhao Y et al. Mutations in CIZ1 cause adult onset primary cervical dystonia. Ann Neurol. 2012; 71: 458-69.
31. Defazio G, Abbruzzese G, Aniello MS et al. Eye symptoms in relatives of patients with primary adult-onset dystonia. Mov Disord. 2012; 27: 305-57.
32. Defazio G, Martino D, Abbruzzese G et al. Influence of coffee drinking and cigarette smoking on the risk of primary late onset blepharospasm: evidence from a multicentre case control study. J Neurol Neurosurg Psychiatry. 2007; 78: 877-9.
33. Khooshnoodi MA, Factor SA, Jinnah HA. Secondary blepharospasm associated with structural lesions of the brain. J Neurol Sci. 2013; 331: 98-101.
34. Rana AQ, Kabir A, Dogu O et al. Prevalence of blepharospasm and apraxia of eyelid opening in patients with parkinsonism, cervical dystonia and essential tremor. Eur Neurol. 2012; 68: 318-21.
35. Zadori D, Veres G, Szalardy L et al. Druginduced movement disorders. Expert Opin Drug Saf. 2015; 14: 877-90.
36. Valls-Sole J, Montero J. Movement disorders in patients with peripheral facial palsy. Mov Disord. 2003; 18: 1424-35.
37. Berardelli A, Rothwell JC, Day BL, Marsden CD. Pathophysiology of blepharospasm and oromandibular dystonia. Brain. 1985; 108: 593-608.
38. Conte A, Defazio G, Ferrazzano G et al. Is increased blinking a form of blepharospasm? Neurology. 2013; 80: 2236-41.
39. Quartarone A, Morgante F, Sant’angelo A et al. Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia. J Neurol Neurosurg Psychiatry. 2008; 79: 985-90.
40. Feiwell RJ, Black KJ, McGee-Minnich LA et al. Diminished regional cerebral blood flow response to vibration in patients with blepharospasm. Neurology. 1999; 52: 291-7.
41. Dresel C, Haslinger B, Castrop F et al. Silent event-related fMRI reveals deficient motor and enhanced somatosensory activation in orofacial dystonia. Brain. 2006; 129: 36-46.
42. Yang J, Luo C, Song W et al. Diffusion tensor imaging in blepharospasm and blepharospasm-oromandibular dystonia. J Neurol. 2014; 261: 1413-24.
43. Henderson JW. Essential blepharospasm. Trans Am Ophthalmol Soc. 1956; 54: 453-520.
44. Nutt JG, Hammerstad JP, deGarmo P, Carter J. Cranial dystonia: double-blind crossover study of anticholinergics. Neurology. 1984; 34: 215-7.
45. Gurdjian ES, Williams HW. The surgical treatment of intractable blepharospasm. JAMA. 1928; 91: 2053-6.
46. Coleman CC. Surgical treatment of facial spasm. Ann Surg. 1937; 105: 638-57.
47. Greenwood J. The surgical treatment of hemifacial spasm. J Neurosurg. 1946; 3: 506-10.
48. Gillum WN, Anderson RL. Blepharospasm surgery: anatomic approach. Arch Ophthalmol. 1981; 99: 1056-62.
49. Anderson RL, Patel BC, Holds JB et al. Blepharospasm: past, present, and future. Ophthal Plast Reconstr Surg. 1998; 14: 305-7.
50. Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology. 1980; 87: 1044-9.
51. Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol. 1985; 103: 347-50.
52. Simpson DM, Hallett M, Ashman EJ et al. 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. 2016; 86: 1818-26.
53. Bilyk JR, Yen MT, Bradley EA et al. Chemodenervation for the Treatment of Facial Dystonia: A Report by the American Academy of Ophthalmology. Ophthalmology. 2018; 125(9): 1459-67.
54. Pellizzari R, Rossetto O, Schiavo G, Montecucco C. Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses. Philos Trans R Soc Lond B Biol Sci. 1999; 354: 259-68.
55. Dressler D, Pan L, Adib Saberi F. Antibody-induced failure of botulinum toxin therapy: re-start with low-antigenicity drugs offers a new treatment opportunity. J Neural Transm (Vienna). 2018; 125(10): 1481-6.
56. Jost WH, Kohl A. Botulinum toxin: evidence based medicine criteria in blepharospasm and hemifacial spasm. J Neurol. 2001; 248(1): 21-4.
57. Albanese A, Bentivoglio AR, Colosimo C et al. Pretarsal injections of botulinum toxin improve blepharospasm in previously unresponsive patients. J Neurol Neurosurg Psychiatry. 1996; 60: 693-4.
58. Levy RL, Berman D, Parikh M, Miller NR. Supramaximal doses of botulinum toxin for refractory blepharospasm. Ophthalmology. 2006; 113(9): 1665-8.
59. Ochudło S, Bryniarski P, Opala G. Botulinum toxin improves the quality of life and reduces the intensification of depressive symptoms in patients with blepharospasm. Parkinsonism Relat Disord. 2007; 13(8): 505-8.
60. Calace P, Cortese G, Piscopo R et al. Treatment of blepharospasm with botulinum neurotoxin type A: long-term results. Eur J Ophthalmol. 2003; 13(4): 331-6.
61. Dressler D, Karapantzou C, Rohrbach S et al. Frontalis suspension surgery to treat patients with blepharospasm and eyelid opening apraxia: long-term results. J Neural Transm (Vienna). 2017; 124(2): 253-7.
62. Reese R, Gruber D, Schoenecker T et al. Long-term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation. Mov Disord. 2011; 26: 691-8.
63. Lorenzano D, Tansley S, Ezra DG. Sensory Trick Frames: A New Device for Blepharospasm Patients. J Mov Disord. 2019; 12(1): 22-6.
64. Macerollo A, Superbo M, Gigante AF et al. Diagnostic delay in adult-onset dystonia: data from an Italian movement disorder center. J Clin Neurosci. 2015; 22(3): 608-10.