КОМОРБИДНЫЙ ПАЦИЕНТ – СОВРЕМЕННЫЙ ВЗГЛЯД НА ПРОБЛЕМУ. ХРОНИЧЕСКАЯ ИШЕМИЯ МОЗГА КАК МЕЖДИСЦИПЛИНАРНАЯ ПРОБЛЕМА (обзор литературы)
Ключевые слова:
хроническая ишемия мозга (ХИМ), неврология, цереброваскулярные заболевания (ЦВЗ).Аннотация
Введение. Хроническая ишемия мозга (ХИМ) – наиболее частая форма цереброваскулярных заболеваний (ЦВЗ), представляющая собой «зонтичный» диагноз, объединяющий этиологически и патогенетически разнородную группу клинических состояний, которые развиваются в результате сосудистого поражения головного мозга, не связанного с перенесенными инсультами.
Цель исследования. Изучение современных литературных данных о патогенезе и факторах риска развития ХИМ, механизмах действия препарата Мексидол (этилметилгидроксипиридина сукцинат) на различные звенья патогенеза при неврологических нарушениях у больных с ХИМ, в том числе с коморбидностью.
Методы. Систематический поиск осуществлен в таких электронных библиографических базах данных, как PubMed, MEDLINE, Google Scholar, в электронном ресурсе на русскоязычных, англоязычных сайтах, и на официальных интернет-страницах медицинских журналов по опубликованным в открытом доступе статьям по проблеме ХИМ (этиологии, патогенезу, диагностическим критериям), а также Мексидол и Мексидол ФОРТЕ 250. Проанализированы статьи, опубликованные в период с 2000 по 2022 годы. Критерии включения: рандомизированные контролируемые исследования, метаанализы и оригинальные исследования. Критерии исключения: исследования с низким уровнем достоверности, ретроспективные исследования, научные обзоры, систематические отчеты и клинические случаи.
Результаты и обсуждение. Терапия Мексидолом приводила к значимому регрессу выраженности таких важных проявлений ХИМ, как когнитивные, эмоциональные, вегетативные и двигательные нарушения. Дополнительным косвенным признаком эффективности терапии препаратом может являться высокая приверженность пациентов лечению. Основным преимуществом антиоксиданта, антигипоксанта и мембранопротектора Мексидола является мультимодальность воздействия, что способствует его эффективному использованию при коморбидной патологии с ХИМ.
Выводы. Клиническая эффективность, безопасность применения и хорошая переносимость Мексидола, позволяют рекомендовать длительную последовательную терапию в виде инъекций в течение 2-х недель, с последующим переходом на таблетированную форму в течение двух месяцев, для лечения пациентов с ХИМ, в том числе с коморбидностью.
Библиографические ссылки
00-2019. Available from: https://www.who.int/ru/news/item/09-12-2020-who-reveals-leading-causes-of-death-and-disability-worldwide-2000-2019
2. Pantoni L, Garcia J. Pathogenesis of leukoaraiosis. Stroke. 1997;28:652-659. PMID: 9056627. doi: 10.1161/01.str.28.3.652
3. Martynov AI, Shmyrev VI, Ostroumova OD, et al. Features of white matter lesions in elderly patients with arterial hypertension. Klinicheskaia meditsina = Clinical Medicine. 2000;6:11-15. (In Russ.)
4. Damulin IV, Parfenov VA, Skoromets AA, Yakhno NN. Narusheniia krovoobrashcheniia v golovnom i spinnom mozge. V kn.: Bolezni nervnoi sistemy. Rukovodstvo dlia vrachei. N.N. Iakhno, D.R. Shtulman (red.). [Disorders of cerebral and spinal circulation. In: Diseases of the nervous system. A guide for physicians. NN Yakhno, DR Shtulman (eds.)]. Moscow, 2003:231-302
5. Levin OS. Discirculatory encephalopathy: an anachronism or a clinical reality? Sovremennaia terapiia v psikhiatrii i nevrologii = Modern therapy in psychiatry and neurology. 2012;3:40-46. (In Russ.)
6. Levin OS. Discirculatory encephalopathy: modern concepts of development mechanisms and treatment. Consilium Medicum. 2007;8:72-79. (In Russ.)
7. Zakharov VV, Vakhnina NV. Diagnosis and treatment of chronic cerebral ischemia (clinical case analysis). Meditsinskii sovet = Medical council. 2018;18:44-49. (In Russ.). doi.org/10.21518/2079-701X-2018-18-44-49
8. Yakhno NN, Damulin IV, Zakharov VV. Discirculatory encephalopathy. Moscow, 2000:32
9. Kearney-Schwartz A, Rossignol P, Bracard S, Felblinger J, Fay R, Boivin JM, Lecompte T, Lacolley P, Benetos A, Zannad F. Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints. Stroke. 2009 Apr;40(4):1229-36. doi: 10.1161/STROKEAHA.108.532853. Epub 2009 Feb 26. PMID: 19246701
10. Levin OS. Diagnostika i lechenie distsirkuliatornoi entsefalopatii. Met. Posobie. [Diagnosis and treatment of discirculatory encephalopathy. Methodological manual]. Moscow, 2010:8
11. Chukanova EI, Khodzhamdzharov BE, Chukanova AS. Chronic cerebral ischemia (etiology, pathogenesis, treatment). Prevention of stroke and vascular dementia. Russki meditsinskii zhurnal = RMJ. 2012;12:517. (In Russ.)
12. Levin OS, Damulin IV. Diffuznye izmeneniia belogo veshchestva (leikoareoz) i problema sosudistoi dementsii. V kn.: Dostizheniia v neirogeriatrii. Pod red. N.N. Iakhno, I.V. Damulina. [Diffuse changes in white matter (leukoaraiosis) and the problem of vascular dementia. In: Achievements in neurogeriatrics. Eds. NN Yakhno, IV Damulin]. Moscow: MMA, 1995:189–231
13. de Groot V, Beckerman H, Lankhorst GJ, Bouter LM. How to measure comorbidity. a critical review of available methods. J Clin Epidemiol. 2003 Mar;56(3):221-9. doi: 10.1016/s0895-4356(02)00585-1. PMID: 12725876
14. Putilina MV. Comorbidity in the elderly. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2016;5:106-111. (In Russ.)
15. Feinstein AR. THE PRE-THERAPEUTIC CLASSIFICATION OF CO-MORBIDITY IN CHRONIC DISEASE. J Chronic Dis. 1970 Dec;23(7):455-68. doi: 10.1016/0021-9681(70)90054-8. PMID: 26309916
16. Vertkin AL, Rumyantsev MA, Skotnikov AS. Comorbidity. Klinicheskaia meditsina = Clinical medicine. 2012;10:4-11. (In Russ.). URL: https://cyberleninka.ru/article/n/komorbidnost
17. Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, Meinow B, Fratiglioni L. Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev. 2011 Sep;10(4):430-9. doi: 10.1016/j.arr.2011.03.003. Epub 2011 Mar 23. PMID: 21402176
18. Valderas JM, Starfield B, Sibbald B, Salisbury C, Roland M. Defining comorbidity: implications for understanding health and health services. Ann Fam Med. 2009 Jul-Aug;7(4):357-63. doi: 10.1370/afm.983. PMID: 19597174; PMCID: PMC2713155
19. Drapkina OM, Shutov AM, Efremova EV. Comorbidity, multimorbidity, dual diagnosis - synonyms or different concepts? Kardiovaskuliarnaia terapiia i profilaktika = Cardiovascular therapy and prevention. 2019;18(2):65-6. (In Russ.)
20. Chamorro A, Dirnagl U, Urra X, Planas AM. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurology. 2016;15(18):869-881. doi.org/10.1017/cjn.2021.223
21. Ramanathan M., Abdul K.K., Justin A. Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice // Behavioral Pharmacology. 2016;27(7):615-622. doi: 10.1097/fbp.0000000000000256
22. Bon EI, Maksimovich NE. The role of excitotoxicity in the pathogenesis of brain damage in ischemia. Vestnik Smolenskoi gosudarstvennoi meditsinskoi akademii = Bulletin of the Smolensk State Medical Academy. 2019;1. (In Russ.). URL: https://cyberleninka.ru/article/n/rol-eksaytotoksichnosti-v-patogeneze-povrezhdeniy-golovnogo-mozga-pri-ishemii
23. O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST. Vascular cognitive impairment. Lancet Neurol. 2003 Feb;2(2):89-98. doi: 10.1016/s1474-4422(03)00305-3. PMID: 12849265
24. Turuspekova ST, Atantaeva EB, Nurgalieva LB, Kalelov ZS. Arterial hypertension as a predictor of dementia syndrome. Meditsina (Almaty) = Medicine (Almaty). 2016;9(171):75-82. (In Russ.)
25. van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P. Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke. 2005 Oct;36(10):2116-20. doi: 10.1161/01.STR.0000179092.59909.42. Epub 2005 Sep 1. PMID: 16141425
26. Yakhno NN, Levin OS, Damulin IV. Comparison of clinical and MRI data in discirculatory encephalopathy. Report 2: cognitive impairment. Nevrologicheskii zhurnal = Neurological Journal. 2001;6(3):10-19. (In Russ.)
27. Vakhnina NV, Zakharov VV. Gait disturbances and postural stability in discirculatory encephalopathy. Zhurnal nevrologii i psikhiatrii imeni SS Korsakova = SS Korsakov Journal of Neurology and Psychiatry. 2017;117(1):78-84. (IN Russ.). oi.org/10.17116/jnevro20171171178-84
28. Dotsenko NY, Boev SS, Shekhunova IA, Gerasimenko LV, Dedova VO. Arterial hypertension as a risk factor for the development of cognitive disorders and issues of secondary prevention. Terapiia = Therapy. 2015;7-8:100. (In Russ.)
29. Larrieu S, Letenneur L, Orgogozo JM. Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology. 2002;59: 594–99. doi.org/10.1212/01.WNL.0000034176.07159.F8
30. Levin OS. Diagnostika i lechenie dementsii v klinicheskoi praktike [Diagnosis and treatment of dementia in clinical practice]. Moscow, Publisher: MedPress-Inform. 2014:248
31. Frisoni GB, Galluzzi S, Bresciani L, et al. Mild cognitive impairment with subcortical vascular features. Clinical characteristics and outcome. Neurol. 2002;249(10):1423–1432. doi:10.1007/s00415-002-0861-7
32. Preobrazhenskaya IS, Yakhno NN. Vascular cognitive disorders: clinical manifestations, diagnosis, treatment. Nevrologicheskii zhurnal = Neurological Journal. 2007;12(5):45-50. (In Russ.)
33. Roman GC, Erkinjuntti T, Wallin A, et al. Subcortical ischemic vascular dementia. Lancet Neurology. 2002;1(7):426-36. doi: 10.1016/s1474-4422(02)00190-4
34. Parfenov VA, Zakharov VV, Preobrazhenskaya IS. Kognitivnye rasstroistva [Cognitive disorders]. Moscow: Remedium Group, 2014:192
35. Yakhno NN, Zakharov VV, Lokshina AB, Koberskaya NN, Mkhitaryan EA. Dementsii: rukovodstvo dlia vrachei. [Dementias: a guide for physicians]. Moscow: MedPress-Inform, 2011:264
36. Kamchatnov PR, Vorobyeva OV, Rachin AP. Correction of emotional and cognitive disorders in patients with chronic cerebral ischemia. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2014;114(4):52-56. (In Russ.)
37. Bryzhakhina VG, Damulin IV. Stato locomotor disturbances in elderly patients with discirculatory encephalopathy and dementia. Vestnik prakticheskoi nevrologii = Practical Neurology Bulletin. 2003;7:17-21. (In Russ.)
38. Bryzhakhina VG, Damulin IV, Yakhno NN. Gait and balance disorders in discirculatory encephalopathy. Report 1. Nevrologicheskii zhurnal = Neurological Journal. 2004;9(2):11-16. (In Russ.)
39. Damulin IV, Bryzhakhina VG, Shashkova EV, Yakhno NN. Gait and balance disorders in discirculatory encephalopathy. Report 2. Clinical-morphological and MRI comparisons. Nevrologicheskii zhurnal = Neurological Journal. 2004;9(4):13-18. (In Russ.)
40. Yakhno NN, Levin OS, Damulin IV. Comparison of clinical and MRI data in discirculatory encephalopathy. Report 1: motor disturbances. Nevrologicheskii zhurnal = Neurological Journal. 2001;6;2:10–16. (In Russ.)
41. Damulin IV. Bolezn Altsgeimera i sosudistaia dementsiia. Pod red. N.N. Iakhno [Alzheimer's disease and vascular dementia. In: Yakhno NN (Ed)]. Moscow, 2002:85
42. Zakharov VV. Clinic, diagnosis, and treatment of discirculatory encephalopathy. Russkii meditsinskii zhurnal = Russian Medical Journal. 2202009;2:140. (In Russ.)
43. Rockwood K, Wentzel C, Hachinscki V, et al. Prevalence and outcomes of vascular cognitive impairment. Neurology. 2000;54(2):447-451. doi: 10.1212/wnl.54.2.447
44. Bowler JV, Hachinski V. The concept of vascular cognitive impairment. In: Erkinjuntti T, Gauthier S (eds). Vascular cognitive impairment. Martin Dunitz. 2002: 9-26
45. Yakhno NN, Zakharov VV, Lokshina AB. Syndrome of mild cognitive impairment in discirculatory encephalopathy. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2005;105(2):13-17. (In Russ.)
46. Shchulkin AV. Effect of mexidol on the development of the phenomenon of the neuronal excitotoxicity in vitro. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2012;112(2):35‑39. (In Russ.)
47. Voronina TA. Pioneer of antioxidant neuroprotection. 20 years in clinical practice. Russkii meditsinskii zhurnal = Russian Medical Journal. 2016;7:434-438. (In Russ.)
48. Abramenko YV. The influence of mexidol on changes in the lipid-phospholipid profile in elderly patients with acute cerebral circulation disorders. Nevrologiia, neiropsikhiatriia, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(2):68–75. (In Russ.)
49. Mikhaylova SA. Neuroprotection in arterial hypertension and transient ischemic attack. Mexidol in clinic and experiment. Terapiia = Therapy. 2019:214-215. (In Russ.)
50. Sharafutdinova KM, Novikova LB, Sharapova LR. The use of Mexidol in the acute and subacute periods of ischemic stroke. Mexidol in clinic and experiment. Terapiia = Therapy. 2019;226-229. (In Russ.)
51. Berezhnaya SV, Iakupov ÉZ, Zaharov YuA. The efficacy of combination therapy with mexidol and cerebrolysin in chronic cerebral ischemia. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2016;116(5):23‑27. (In Russ.)
https://doi.org/10.17116/jnevro20161165123-27
52. Shishkova VN. Cognitive impairment as a universal clinical syndrome in a therapist”s practice Terapevticheksii arkhiv = Therapeutic Archive. 2014;86(11):128 134. (In Russ.)
53. Torshin IYu, Gromova OA, Sardaryan IS, Fedotova LE. Comparative chemoreactomic analysis of mexidol. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. Special issues. 2017;117(1 2):75 83. (In Russ.)
54. Gromova OA, Torshin IYu, Stakhovskaya LV, Pepelyaev EG, Semenov VA, Nazarenko AG. Experience of mexidol application in neurological practice. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2018;118(10):97–107. (In Russ.). doi: 10.17116/jnevro201811810197
55. Fedin AI, Zakharov VV, Tanashyan MM, Chukanova EI, Majidova EN, Shchepankevich LA, Ostroumova OD. Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO). SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2021;121(11):7–16. (In Russ.). https://doi.org/10.17116/jnevro20211211117
56. Chukanova EI, Chukanova AS, Mamaeva KI. Results of a study of the effectiveness and safety of mexidol in patients with chronic cerebral ischemia. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2015;2:71-74 (In Russ.). doi: 10.17116/jnevro20151152171-74
57. Chukanova EI, Chukanova AS. The effectiveness and safety of Mexidol FORTE 250 in the context of sequential therapy in patients with chronic cerebral ischemia. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2019;119:939-45. (In Russ.). doi.org/10.17116/jnevro201911909139
58. Pugacheva EL. Efficacy of Mexidol in patients with type 2 diabetes mellitus with neurological complications. SS Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2022;122(5):84–89. (In Russ.). https://doi.org/10.17116/jnevro202212205184
59. Shchepankevich LA, Nikolaev YA, Dolgova NA. Optimization of lipid-lowering therapy in patients with ischemic stroke and type 2 diabetes mellitus. S. Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni SS Korsakova. 2016;2:42–45. (In Russ.)
60. Maksyutova LA. The use of mexidol in the therapy of patients with chronic cerebral ischemia against the background of metabolic syndrome in the practice of a general practitioner. Terapiia = Therapy. 2019;389-391 (In Russ.)
