QUANTITATIVE EVALUATION OF FATIGUE IN PATIENTS WITH MYASTHENIA GRAVIS

Kalbus O. I.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

The level and features of fatigue development in patients with myasthenia gravis remain not well studied, but their research is promising in order to improve the therapeutic tactics, social, domestic, professional adaptation and, as a consequence, the quality of life of patients in general. The purpose of this work was to quantify the fatigue parameters in patients with myasthenia gravis depending on the form and class of the disease, as well as on the immunological type of the disease. Object and methods. 182 patients with myasthenia were examined (147 (80.8%) patients with a generalized form of the disease, 35 (19.2%) – with ocular form). Clinical and neurological examination included complaints collection, history of disease and life, neurological examination. To evaluate the clinical form of myasthenia, the MGFA classification was used. For a quantitative assessment of fatigue, the Fatigue Severity Scale (FSS) was used. The assessment of the level of antibodies to acetylcholine receptors (AchR) and muscle-specific tyrosine kinase (MuSK) by ELISA was performed to all patients, as well as determination of antibodies to titin and SOX1 by indirect immunofluorescence method. In mathematical processing of data, methods of parametric and nonparametric statistics were used. Results and discussion. Among the surveyed patients by gender, women predominated — 128 (70.3%), the number of men was 54 (29.7%), the ratio of women to men — 2.37:1. Antibodies to acetylcholine receptors were detected in 68.1% of the patients in the general sample (in 73.5% patients with generalized form and in 45.7% - with an ocular form). Antibodies to muscle-specific tyrosine-kinase were detected in 16% of the total number of patients. These antibodies were not detected in patients with ocular myasthenia. Antibodies to titin were detected in almost a third of all subjects - 53 (29.1%). These antibodies were not detected in patients with ocular form of myasthenia gravis. Antibodies to SOX1 were not detected in patients with ocular myasthenia, but diagnosed in 5.5% patients with generalized form. The level of fatigue in patients increases with the increase of the MGFA class of the disease. The median fatigue rate in the general sample corresponded to a mild fatigue level (FSS:36- 44 points), and in patients with generalized myasthenia, it was consistent with moderate fatigue (FSS: 45-53 points). In patients with ocular myasthenia, median fatigue was significantly lower in comparison with the general sample and with the generalized form and did not reach the clinical value (p<0.001). When performing some comparisons by Spirmen’s rank correlation method, it was found that fatigue correlates with the presence of antibodies to AchR (ρ = 0,22; p <0,05) and with their titer (ρ=0,46; p <0,0001), to a lesser extent - with the presence of antibodies to titin (ρ=0.15; p <0.05). No correlations found between fatigue level and the presence or the titre of antibodies to MuSK (ρ = 0,07; p> 0,05; ρ = 0,08; p> 0,05, respectively), as well as the presence of antibodies to SOX1 (ρ = 0.06; p> 0.05). Fatigue significantly correlated with the clinical form of myasthenia (generalized) (ρ = -0,55; p <0,05), myasthenia class for MGFA (ρ = -0,32; p <0,05) and subclass of the disease (subclass B) (ρ = -0.38; p <0.05). Conclusions. The level of antibodies to acetylcholine receptors impact the degree of fatigue in patients with myasthenia gravis. The degree of fatigue in patients with ocular form did not reach clinically significant levels, as opposed to patients with a generalized form. In the generalized form of myasthenia there was a significant fatigue level increase with an increase of the MGFA class of disease, which reached a clinically meaningful level in all classes of the disease regardless of subclass.

myasthenia, fatigue, antibody, class, subclass, generalized form, ocular form.

1. Kulikova SL. Antitela k acetilholinovym receptoram v diagnostike razlichnyh form miastenii. Nevrologija i nejrohirurgija Vostochnaja Evropa. 2014;1(21):73-82. [in Russiаn].
2. Sanadze AG. Miastenija i miastenicheskie sindromy: rukovodstvo. M.: GJeOTAR-Media; 2017. 256 s. [in Russiаn].
3. Shkol’nik VM, Kal’bus AI, Baranenko AN, Pogorelov AV. Miastenija: sovremennye podhody k diagnostike i lecheniju. Ukrainskij nevrologicheskij zhurnal. 2014;2:12-7. [in Russiаn].
4. Andersen JB, Heldal AT, Engeland A, Gilhus NE. Myasthenia gravis epidemiology in a national cohort; combining multiple disease registries. Acta neurologica Scandinavica. Supplementum. 2014;198:26-31. Available from: https://doi.org/10.1111/ane.12233
5.  Blum S, Lee D, Gillis D, McEniery DF, Reddel S, McCombe P. Clinical features and impact of myasthenia gravis disease in Australian patients. Journal of Clinical Neuroscience. 2015;22(7):1164-9. Available from: https://doi.org/10.1016/j.jocn.2015.01.022
6. Breiner A, Widdifield J, Katzberg HD, Barnett C, Bril V, Tu K. Epidemiology of myasthenia gravis in Ontario, Canada. Neuromuscular Disorders. 2016;26(1):41-6. Available from: https://doi.org/10.1016/j.nmd.2015.10.009
7.  Breiner A, Young J, Green D, Katzberg HD, Barnett C, Bril V, et al. Canadian administrative health data can identify patients with myasthenia gravis. Neuroepidemiology. 2015;44:108-13. Available from: https://doi.org/10.1159/000375463
8. Carr AS, Cardwell CR, McCarron PO, McConville J. A systematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurology. 2010;10:46. Available from: https://doi.org/10.1186/1471-2377-10-46
9. Skeiea GO, Apostolskib S, Evolic A, Gilhus NE, Illa I, Harms L, et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur. J. Neur. 2010;17:1-10. Available from: https://doi.org/
10. 1111/j.1468-1331.2010.03019.x 10. Kalbus OI. Vyvchennia yakosti zhyttia ta tryvozhnosti u khvorykh na miasteniiu (kliniko-paraklinichne spivstavlennia). ScienceRise: Medical Science. 2018;3(23):10-3. Dostupno: https://doi.org/10.15587/2519-4798.2018.127557 [in Ukrainian].
11.  Kalbus OI. Otsinka yakosti zhyttia khvorykh na miasteniiu. ScienceRise: Medical Science. 2018;2(22):24-7. Dostupno: https://doi. org/10.15587/2519-4798.2018.124132 [in Ukrainian].

«Bulletin of problems biology and medicine» Issue 1 Part 2 (149), 2019 year, 147-151 pages, index UDK 616.74+616.8]-009.17-036.8

10.29254/2077-4214-2019-1-2-149-147-151