Нервно-мышечные болезни. 2024; 14: 12‑24
Когнитивные и эмоциональные нарушения у взрослых пациентов с миотонической дистрофией 1-го типа
https://doi.org/10.17650/2222-8721-2024-14-2-12-24Аннотация
Введение. Миотоническая дистрофия 1‑го типа (МД1) – наследственное, медленно прогрессирующее мультисистемное заболевание с аутосомно‑доминантным типом наследования, обусловленное экспансией тринуклеотидных (CTG)n повторов в 3’‑нетранслируемой области гена DMPK. Среди клинических проявлений МД1 важное место занимают симптомы поражения центральной нервной системы, в частности когнитивные и эмоциональные нарушения. Цель исследования – оценить характер когнитивных и эмоциональных нарушений у пациентов с разными формами МД1 и их влияние на качество жизни.
Материалы и методы. Обследовано 60 пациентов с генетически подтвержденной МД1 (средний возраст пациентов – 37,0 ± 12,4 года; из них 36 (60,0 %) мужчин). Всем пациентам проводились нейропсихологическое тестирование с использованием Монреальской шкалы оценки когнитивных функций, краткой шкалы оценки психического статуса, Адденбрукской шкалы III, тестов Векслера, построения пути, символьных и цифровых модальностей, 10 слов Лурии, батареи лобной дисфункции, оценка эмоциональных нарушений с помощью госпитальной шкалы оценки тревоги и депрессии, шкалы апатии, оценка качества жизни – 36‑Item Short‑Form Medical Outcomes Study. Магнитно‑резонансная томография головного мозга проведена 53 пациентам с оценкой выраженности поражения белого вещества и атрофии серого вещества.
Результаты. В исследование включено 8 (13,3 %) пациентов с врожденной, 19 (31,7 %) – детской, 33 (55 %) – взрослой формой МД1. У группы пациентов с врожденной формой был самый грубый когнитивный дефицит, особенно в тестах на исполнительные функции и зрительно‑пространственное восприятие. Когнитивные нарушения были выявлены и у пациентов со взрослой формой МД1, но меньшей степени выраженности. По сравнению с контролем у пациентов с МД1 значимо чаще определялась апатия (р = 0,002), а не тревога и депрессия. При МД1 установлено поражение как белого, так и серого вещества головного мозга, выявлена связь поражения серого вещества с депрессией (r = 0,296) и апатией (r = –0,291). На качество жизни в большей степени оказывали влияние эмоциональные нарушения (тревога, r = –0,577; депрессия, r = –0,650; апатия, r = –0,545).
Выводы. У пациентов с МД1 не определен типичный паттерн когнитивных нарушений, страдают различные домены когнитивных функций. Наиболее выраженный когнитивный дефицит характерен для группы пациентов с врожденной формой заболевания. Выявлена связь поражения серого вещества головного мозга с эмоциональными нарушениями, наличие которых, в свою очередь, снижает качество жизни пациентов с МД1.
Список литературы
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2. Itoh K., Mitani M., Kawamoto K. et al. Neuropathology does not correlate with regional differences in the extent of expansion of CTG repeats in the brain with myotonic dystrophy type 1. Acta Histochem Cytochem 2010;43(6):149–56. DOI: 10.1267/ahc.10019
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27. Mammarella I.C., Cornoldi C. Nonverbal learning disability (developmental visuospatial disorder). Handb Clin Neurol 2020;174:83–91. DOI: 10.1016/B978-0-444-64148-9.00007-7
28. Wen W., Sachdev P.S., Li J.J. et al. White matter hyperintensities in the forties: their prevalence and topography in an epidemiological sample aged 44–48. Hum Brain Mapp 2009;30(4):1155–67. DOI: 10.1002/hbm.20586
29. Brusa C., Gadaleta G., D’Alessandro R. et al. Psychopharmacological treatments for mental disorders in patients with neuromuscular diseases: A scoping review. Brain Sci 2022;12(2):176–89. DOI: 10.3390/brainsci12020176
30. Labayru G., Aliri J., Zulaica M. et al. Age-related cognitive decline in myotonic dystrophy type 1: An 11-year longitudinal follow-up study. J Neuropsychol 2020;14(1):121–34. DOI: 10.1111/jnp.12192
Neuromuscular Diseases. 2024; 14: 12‑24
Cognitive and emotional disturbances in adult patients with myotonic dystrophy type 1
https://doi.org/10.17650/2222-8721-2024-14-2-12-24Abstract
Background. Myotonic dystrophy type 1 (DM1) is a hereditary slowly progressive multisystem disease with an autosomal dominant mode of inheritance, caused by the expansion of trinucleotide (CTG)n repeats in the 3’ untranslated region of the DMPK gene. Among the clinical manifestations of DM1, an important place is occupied by symptoms of damage to the central nervous system, in particular cognitive and emotional disorders.
Aim. To evaluate the type of cognitive and emotional impairments in patients with different forms of DM1 and their impact on quality of life.
Materials and methods. 60 patients with genetically confirmed DM1 were examined (average age 37.0 ± 12.4 years; 36 (60.0 %) of them were men). All patients underwent neuropsychological testing using the Montreal Cognitive Rating
Scale, Mini‑Mental State Examination, Addenbrooke’s III, Wechsler tests, pathfinding, symbolic and numeric modalities, Luria’s 10 Words, Frontal Dysfunction Battery; assessment of emotional disturbances using the Hospital Anxiety and Depression Rating Scale and the Apathy Scale; quality of life assessment – 36‑Item Short‑Form Medical Outcomes Study. Brain magnetic resonance imaging was performed in 53 patients to assess the severity of white matter lesions and gray matter atrophy.
Results. The study included 8 (13.3 %) patients with congenital, 19 (31.7 %) – childhood, 33 (55 %) – adult forms of MD1. The group of patients with the congenital form had the most severe cognitive deficits, especially in tests of executive functions and visuospatial perception. Cognitive impairment was also characteristic of the adult form, but to a lesser extent. Compared to controls, patients with DM1 were significantly more likely to exhibit apathy (p = 0.002) rather than anxiety and depression. In DM1, damage to both the white and gray matter of the brain was established, and a connection between damage to the gray matter and depression (r = 0.296) and apathy (r = –0.291) was revealed. The quality of life is largely influenced by emotional disorders (anxiety, r = –0.577; depression, r = –0.650; apathy, r = –0.545).
Conclusion. In patients with DM1, a typical pattern of cognitive impairment has not been identified; different domains of cognitive functions are affected. The greatest cognitive deficit is typical for the group of patients with the congenital form. A connection between damage to the gray matter of the brain and emotional disorders has been revealed.
The presence of the latter reduces the quality of life of patients with DM1.
References
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2. Itoh K., Mitani M., Kawamoto K. et al. Neuropathology does not correlate with regional differences in the extent of expansion of CTG repeats in the brain with myotonic dystrophy type 1. Acta Histochem Cytochem 2010;43(6):149–56. DOI: 10.1267/ahc.10019
3. Gourdon G., Meola G. Myotonic dystrophies: State of the art of new therapeutic developments for the CNS. Front Cell Neurosci 2017;11:101. DOI: 10.3389/fncel.2017.00101
4. Dhaenens C.M., Tran H., Frandemiche M.L. et al. Mis-splicing of Tau exon 10 in myotonic dystrophy type 1 is reproduced by overexpression of CELF2 but not by MBNL1 silencing. Biochim Biophys Acta 2011;1812(7):732–42. DOI: 10.1016/j.bbadis.2011.03.010
5. Modoni A., Silvestri G., Vita M.G. et al. Cognitive impairment in myotonic dystrophy type 1 (DM1): A longitudinal follow-up study. J Neurol 2008;255(11):1737–42. DOI: 10.1007/s00415-008-0017-5
6. De Serres-Bérard T., Pierre M., Chahine M. et al. Deciphering the mechanisms underlying brain alterations and cognitive impairment in congenital myotonic dystrophy. Neurobiol Dis 2021;160:105532. DOI: 10.1016/j.nbd.2021.105532
7. Gallais B., Montreuil M., Gargiulo M. et al. Prevalence and correlates of apathy in myotonic dystrophy type 1. BMC Neurol 2015;15:148. DOI: 10.1186/s12883-015-0401-6
8. Morin A., Funkiewiez A., Routier A. et al. Unravelling the impact of frontal lobe impairment for social dysfunction in myotonic dystrophy type 1. Brain Commun 2022;4(3):fcac111. DOI: 10.1093/braincomms/fcac111
9. Gallais B., Gagnon C., Mathieu J. et al. Cognitive decline over time in adults with myotonic dystrophy type 1: A 9-year longitudinal study. Neuromuscul Disord 2017;27(1):61–72. DOI: 10.1016/j.nmd.2016.10.003
10. Meola G., Sansone V., Perani D. et al. Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2). Neuromuscul Disord 2003;13(10):813–21. DOI: 10.1016/s0960-8966(03)00137-8
11. Antonini G., Soscia F., Giubilei F. et al. Health-related quality of life in myotonic dystrophy type 1 and its relationship with cognitive and emotional functioning. J Rehabil Med 2006;38(3):181–5. DOI: 10.1080/16501970500477967
12. Antonini G., Mainero C., Romano A. et al. Cerebral atrophy in myotonic dystrophy: A voxel based morphometric study. J Neurol Neurosurg Psychiatry 2004;75(11):1611–3. DOI: 10.1136/jnnp.2003.032417
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19. Siqueira G.S.A., Hagemann P.M.S., Coelho D.S. et al. Can MoCA and MMSE be interchangeable cognitive screening tools? A systematic review. Gerontologist 2019;59(6):e743–63. DOI: 10.1093/geront/gny126
20. Gallais B., Gagnon C., Côté I. et al. Reliability of the apathy evaluation scale in myotonic dystrophy type 1. J Neuromuscul Dis 2018;5(1):39–46. DOI: 10.3233/JND-170274
21. Fazekas F., Chawluk J. B., Alavi A. et al. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. Am J Roentgenol 1987;149:351–6. DOI: 10.2214/ajr.149.2.351
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23. Axford M.M., Pearson C.E. Illuminating CNS and cognitive issues in myotonic dystrophy: Workshop report. Neuromuscul Disord 2013;23(4):370–4. DOI: 10.1016/j.nmd.2013.01.003
24. Winblad S., Samuelsson L., Lindberg C. et al. Cognition in myotonic dystrophy type 1: A 5-year follow-up study. Eur J Neurol 2016;23(9): 1471–6. DOI: 10.1111/ene.13062
25. Peric S., Rakocevic Stojanovic V., Mandic Stojmenovic G. et al. Clusters of cognitive impairment among different phenotypes of myotonic dystrophy type 1 and type 2. Neurol Sci 2017;38(3):415–23. DOI: 10.1007/s10072-016-2778-4
26. Okkersen K., Buskes M., Groenewoud J. et al. The cognitive profile of myotonic dystrophy type 1: A systematic review and meta-analysis. Cortex 2017;95:143–55. DOI: 10.1016/j.cortex.2017.08.008
27. Mammarella I.C., Cornoldi C. Nonverbal learning disability (developmental visuospatial disorder). Handb Clin Neurol 2020;174:83–91. DOI: 10.1016/B978-0-444-64148-9.00007-7
28. Wen W., Sachdev P.S., Li J.J. et al. White matter hyperintensities in the forties: their prevalence and topography in an epidemiological sample aged 44–48. Hum Brain Mapp 2009;30(4):1155–67. DOI: 10.1002/hbm.20586
29. Brusa C., Gadaleta G., D’Alessandro R. et al. Psychopharmacological treatments for mental disorders in patients with neuromuscular diseases: A scoping review. Brain Sci 2022;12(2):176–89. DOI: 10.3390/brainsci12020176
30. Labayru G., Aliri J., Zulaica M. et al. Age-related cognitive decline in myotonic dystrophy type 1: An 11-year longitudinal follow-up study. J Neuropsychol 2020;14(1):121–34. DOI: 10.1111/jnp.12192
