Neurophthalmological manifestations in Steinert´s disease
Keywords:
Christmas tree cataract, retinal pigment epithelium dystrophy, retinal dystrophy, myotonic dystrophy type 1, electroculogram, electroretinogram, Steinert's disease, neurophthalmological manifestations, ophthalmoparesis, eyelid ptosisAbstract
Objective: To describe the neuro-ophthalmological manifestations and the functional state of the retina in patients with Steinert's disease.
Methods: An observational, descriptive study was carried out on a series of 29 patients, from January 18, 2016 to January 15, 2018, in the Neurophthalmology service at Prof. Rafael Estrada González Neurology and Neurosurgery Institute. Demographic, clinical variables, as well as functional electrophysiological evaluation variables of the retina were taken into account. Univariate and multivariate statistical analysis was performed.
Results: The mean age of the patients was 37.69 years (± 11.48); the most frequent age group was 40 to 49 years (44.8%) and the composition was similar in terms of sex. Mean visual acuity was 87.2 VAR (± 2.842), and 74.1% considered good, as was color vision (72.4%), contrast sensitivity at 1 meter (63.8 %) and 3 meters (62.1%). Ocular hypotension (82.8%), cataracts (58.64%), palpebral ptosis (51.7%), ophthalmoparesis (34.5%), epiretinal membranes (12.1%) and maculopathies (8.64%) were detected. The mesopic electroretinogram was altered in 75.9% of the patients and the electroculogram in 39.7%.
Conclusions: Structural and functional ophthalmological alterations were found in patients with Steinert's disease. The evident affectation, detected in the visual electrophysiology tests, suggests an important dysfunction of the photoreceptor layer of the retina and its pigment epithelium (greater in the former), unlike that described historically in this disease.
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References
1. Ropper AH, Samuels MA. Adams y Victor. Principios de Neurología. 9 Ed. Boston: McGraw-Hill´s Inc.; 2011. p. 1366-83.
2. Hahn C, Salajegheh MK. Myotonic disorders: A review article. Iran J Neurol. 2016 [citado: 30/08/2020];15(1):46-53. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852070/
3. Sellier C, Cerro-Herreros E, Blatter M, Freyermuth F, Gaucherot A, Ruffenach F, et al. rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences. Nat Commun. 2018;9(1):2009. Doi: 10.1038/s41467-018-04370-x.
4. Johnson NE. Myotonic Muscular Dystrophies. Continuum (Minneap Minn). 2019;25(6):1682-95. Doi: 10.1212/CON.0000000000000793.
5. U.S. National Library of Medicine. Myotonic dystrophy; 2020 [citado: 26/08/2020]. Disponible en: https://ghr.nlm.nih.gov/condition/myotonic-dystrophy#
6. Online Mendelian Inheritance in Man, OMIM®. MYOTONIC DYSTROPHY 2; DM2. Johns Hopkins University, Baltimore, MD. Número MIM: 160900; 2017. [citado: 26/08/2020]. Disponible en: https://omim.org/entry/602668?search=myotonic%20dystrophy&highlight=%28myotonia%7Cmyotonic%29%20dystrophy
7. Kevin Yum K, Wang ET, Kalsotra A. Myotonic Dystrophy: Disease Repeat Range, Penetrance, Age of Onset, and Relationship Between Repeat Size and Phenotypes. Curr Opin Genet Dev. 2017;44:30-7. Doi: 10.1016/j.gde.2017.01.007
8. Wenninger S, Montagnese F, Schoser B. Core Clinical Phenotypes in Myotonic Dystrophies. Front Neurol. 2018;9:303. Doi: 10.3389/fneur.2018.00303
9. LoRusso S, Weiner B, Arnold WD. Myotonic Dystrophies: Targeting Therapies for Multisystem Disease. Neurotherapeutics. 2018;15(4):872-84. Doi: 10.1007/s13311-018-00679-z
10. Hilbert JE, Barohn RJ, Clemens PR, Luebbe EA, Martens WB, McDermott MP, et al. High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2. Neurology. 2017;89(13):1348-54. Doi: 10.1212/WNL.0000000000004420
11. Knight AK, Tidehag L, Mattsson G, Magnusson P. Myotonic dystrophy type 1 - a rare cause of bradycardia in the young. Lakartidningen. 2020 [citado: 20/08/2020];117:FR47. Disponible en: https://europepmc.org/article/med/31961442
12. Comas-Valdespino RL, Landrian-Davis A, Serra Ruíz M. Distrofia miotónica de Steinert. Presentación de un caso. Medisur. 2017 [citado: 20/08/2020];15(1). Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1727-897X2017000100016&nrm=iso
13. van der Velden BG, Okkersen K, Pc Kessels R, Groenewoud J, van Engelen B, Knoop H, et al. Affective symptoms and apathy in myotonic dystrophy type 1 a systematic review and meta-analysis. J Affect Disord. 2019;250:260-9. Doi: 10.1016/j.jad.2019.03.036.
14. Lagrue E, Dogan C, De Antonio M, Audic F, Bach N, Barnerias C. A large multicenter study of pediatric myotonic dystrophy type 1 for evidence-based management. Neurology. 2019;92(8):e852-e865. Doi: 10.1212/WNL.0000000000006948.
15. Angeard N, Huerta E, Jacquette A, Cohen D, Xavier J, Gargiulo M, et al. Childhood-onset form of myotonic dystrophy type 1 and autism spectrum disorder: Is there comorbidity? Neuromuscul Disord. 2018;28(3):216-21. Doi: 10.1016/j.nmd.2017.12.006.
16. Kersten H, Roxburgh R, Danesh-Meyer H. Ophthalmic manifestations of inherited neurodegenerative disorders. Nat Rev Neurol. 2019 [citado: 20/08/2020];10:349-62. Disponible en: https://www.nature.com/articles/nrneurol.2014.79
17. Kang MJ, Yim HB, Hwang HB. Two cases of myotonic dystrophy manifesting various ophthalmic findings with genetic evaluation. Indian J Ophthalmol. 2016;64(7):535-7. Doi: 10.4103/0301-4738.190157
18. Dalvin LA, Shields CL, Pulido JS, Sioufi K, Cohen V, Shields JA. Uveal Melanoma Associated with Myotonic Dystrophy. A Report of 6 Cases. JAMA Ophthalmol. 2018;136(5):543-7. Doi: 10.1001/jamaophthalmol.2018.0554.
19. Santiesteban-Freixas R, Aguilera-Pacheco O, Francisco-Plasencia M, Luis-Gonzalez S. Enfermedad de Steinert. Manifestaciones oftalmológicas. Rev. Cubana Oftalmol. 1995;8(1):8-12.
20. Landfeldt E, Nikolenko N, Jimenez-Moreno C, Cumming S, Monckton DG, Gorman G, et al. Disease burden of myotonic dystrophy type 1. J Neurol. 2019;266(4):998-1006. Doi: 10.1007/s00415-019-09228-w.
21. Choi SH, Yang HK, Hwang JM, Park KS. Ocular Findings of Myotonic Dystrophy Type 1 in the Korean Population. Graefes Arch Clin Exp Ophthalmol. 2016;254:1189-93. Doi: https://doi.org/10.1007/s00417-016-3266-5
22. Ikeda KS, Iwabe-Marchese C, França MC, Nucci N, Monteiro de Carvalho K. Myotonic dystrophy type 1: frequency of ophthalmologic findings. Arq. Neuro-Psiquiatr. 2016;74(3). Doi: https://doi.org/10.1590/0004-282X20150218
23. Vanacore N, Rastelli E, Antonini G, Bianchi MLE, Botta A, Bucci E, et al. An Age-Standardized Prevalence Estimate and a Sex and Age Distribution of Myotonic Dystrophy Types 1 and 2 in the Rome Province, Italy. Neuroepidemiology. 2016;46:191-7. Doi: https://doi.org/10.1159/000444018
24. Spaziani M, Semeraro A, Bucci E, Rossi F, Garibaldi M, Papassifachis MA, et al. Hormonal and metabolic gender differences in a cohort of myotonic dystrophy type 1 subjects: a retrospective, case–control study. Journal of Endocrinological Investigation. 2020;43:663-75. Doi: 10.1007/s40618-019-01156-w#citeas
25. Pagoulatos D, Kapsala Z, Makri OE, Georgakopoulos CD. Christmas tree cataract and myotonic dystrophy type 1. Eye (Lond). 2018;32(11):1794-5. Doi: 10.1038/s41433-018-0161-9.
26. Ekström AB, Tulinius M, Aring E. Visual Function in Congenital and Childhood Myotonic Dystrophy Type 1. Ophthalmology. 2011;117(5):976-82. Doi: https://doi.org/10.1016/j.ophtha.2010.01.055
27. Rubin GS. Visual Acuity and Contrast Sensitivity. In: Schachat AP editor. Ryan´s Retina. 6th Edition. China: Elsevier Inc.; 2018. p. 340-6.
28. Garcia Filho CA, Santos T, Siqueira AK, Doi M, Soares LA. Intraocular pressure, corneal thickness, and corneal hysteresis in Steinert’s myotonic dystrophy. Arq Bras Oftalmol. 2011;74(3):161-2. Doi: https://doi.org/10.1590/S0004-27492011000300002.
29. Rosa N, Lanza M, Borrelli M, Filosa ML, De Bernardo M, Ventriglia VM, et al. Corneal thickness and endothelial cell characteristics in patients with myotonic dystrophy. Ophthalmology. 2010;117(2):223-5. Doi: https://doi.org/10.1016/j.ophtha.2009.07.003
30. De Bernardo M, Russo V, Rosa N. OPINION Ophthalmological findings in myotonic dystrophy. Arq. Neuro-Psiquiatr. 2017;75(5). Doi: http://dx.doi.org/10.1590/0004-282x20170045.
31. Rao RC, Choudhry N. A Christmas Tree Cataract. J Ophthalmol. 2016;51(6):e160-e161. Doi: 10.1016/j.jcjo.2016.03.005
32. Natung T, Thangkhiew L, Keditsu A, Shullai W. Christmas Tree Cataract - A Cataract that Glitters. J Clin Diagn Res. 2016;10(4):NJ01-NJ02. Doi: 10.7860/JCDR/2016/18923.7580
33. Huguet A, Medja F, Nicole A, Vignaud A, Guiraud-Dogan C, Ferry A, et al. Molecular, Physiological, and Motor Performance Defects in DMSXL Mice Carrying >1,000 CTG Repeats from the Human DM1 Locus. PLoS Genetics. 2012;8(11):e1003043. Doi: 10.1371/journal.pgen.1003043
34. Magaña JJ, Leyva-García N, Cisneros B. Pathogenesis of myotonic dystrophy type 1. Gac Med Mex. 2009 [citado: 08/09/2020];145(4):331-7. Disponible en: https://pubmed.ncbi.nlm.nih.gov/20073433/
35. Rodríguez N, Solis A, Rodriguez D, Gonzalez VC. Structural and funcional findings measured with macular OCT and microperimetry in presymptomatic patients with myotonic dystrophy type 1. Invest. Ophthalmol. Vis. Sci. 2018 [citado: 08/09/2020];59(9):1537. Disponible en: https://iovs.arvojournals.org/article.aspx?articleid=2689948
36. Bird TD. Myotonic Dystrophy Type 1. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021. 2019 [citado: 07/09/2020]. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK1165/
37. Dogan C, De Antonio M, Hamroun D, Varet H, Fabbro M, Rougier F, et al. Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study. PLoS One. 2016;11(2):e0148264. Doi: 10.1371/journal.pone.0148264.
38. Abed E, D'Amico G, Rossi S, Perna A, Bianchi MLE, Silvestri G. Spectral domain optical coherence tomography findings in myotonic dystrophy. Neuromuscular Disorders. 2020;30(2):144-50.
39. Hernandez-Hernandez O, Guiraud-Dogan C, Sicot G, Huguet A, Luilier S, Steidl E, et al. Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour. Brain. 2013 [citado: 08/09/2020];136(3):957-70. Disponible en: https://academic.oup.com/brain/article/136/3/957/318229
40. Tian M, Xu CS, Montpetit R, Kramer RH. Rab3A mediates vesicle delivery at photoreceptor ribbon synapses. J Neurosci. 2012 [citado: 08/09/2020];32(20):6931-6. Doi: 10.1523/JNEUROSCI.0265-12.2012
41. Sohn EH, Mullins RF, Stone EM. Macular Dystrophies. In: Schachat AP editor. Ryan´s Retina. 6th Edition. China: Elsevier Inc.; 2018. p. 953-96
42. Constable PA, Bach M, Frishman LJ, Jeffrey BG, Robson AG; International Society for Clinical Electrophysiology of Vision. ISCEV Standard for clinical electro-oculography (2017 update). Doc Ophthalmol. 2017 Feb;134(1):1-9. Doi: 10.1007/s10633-017-9573-2.
