Delva I. І., Vesnina L. E., Mamontova T. V

PROFILE OF BLOOD SYSTEMIC INFLAMMATORY MARKERS AND TIME-BASED CHARACTERISTICS OF POSTSTROKE FATIGUE


About the author:

Delva I. І., Vesnina L. E., Mamontova T. V

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

Post-stroke fatigue (PSF) is very common after stroke and is strongly related to poor quality of life, independent of depression and disability. PSF is heterogeneous phenomenon. During acute stroke period PSF is associated predominantly with biological factors, while at chronic stroke period PSF is connected, as rule, with emotional and behavioral factors. In recent years, among biological risk factors for PSF occurrence is being considered post-ischemic inflammatory response.Aim: to study the dynamic patterns of blood systemic inflammatory markers depending on the time of PSF onset and PSF clinical course. Object and methods. We recruited in the study 49 patients with ischemic acute cerebrovascular events (ACE) – strokes and transient ischemic attacks. PSF was diagnosed by use of questionnaire – Fatigue Assessment Scale. On the ground of the time-based PSF characteristics we conditionally divided all PSF cases as early PSF (that manifested within the first month after ACE onset with subsequent self-resolution not later than at 3 months time-point observation), persistent PSF (that manifested within the first post-stroke month and was still present at 3 months timepoint observation) and late PSF (that manifested at 3 months after ACE onset or later). It was included 15 patients with early PSF, 15 patients with persistent PSF and 9 patients with late PSF. Control group consisted of 10 patients without PSF. Diagnosis of PSF presence/absence and simultaneous measurement of systemic inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1 β, IL-6) in blood serum by ELISA method was carried out at the certain time points after ACE onset. Variables were expressed as mediana (Me) and interquartile (25%-75%) range (Q1- Q3). Data were evaluated using non-parametric comparisons (Mann-Whitney, Friedman, Wilcoxon, Newman-Keuls tests). A p-value less than 0,05 was considered statistically significant. Results and discussion. Within the first 3 days after ACE onset, regardless of presence (absence) of PSF, all patients had much less identical elevated mean CRP level (within the range of 27,8 (25,3-29,2) mg/l to 29,0 (26,8-30,3) mg/l). However, in the next months, dynamics of changes in mean CRP concentration were significantly different, depending on PSF presence and on PSF duration. In the non-PSF patients, mean CRP level was significantly lowered already at 1 month after ACE onset (to 14,6 (5,4-23,0) mg/l) compared to baseline values. In the patients with early PSF, at 3 months time-point observation, on the background of self-resolved PSF, mean CRP level was significantly reduced (to 15,5 (12,7-22,9) mg/l) compared to the previous two measurements (at the first 3 days and at 1 month after PSF onset) and compared with mean value of CRP concentration in the patients with persistent PSF at 3 months after ACE onset (28,3 (24,8-32,4) mg/l). In the patients with persistent PSF, mean CRP level was significantly reduced only at 6 months time-point observation (to 13,3 (7,3-23,0) mg/l), compared with the all three previous measurements. In the patients with late PSF, mean CRP level was relatively low (12,3 (4,8-21,8) mg/l) and practically didn’t differ from mean CRP serum value in the non-PSF patients at 1 month after the ACE onset. Mean L-1β levels were stable during the whole observation period with the exception for the patients with persistent PSF who had significant serum IL-1β elevation at 1 month time-point observation (to 24,0 (20,5-25,5) pg/l), compared with the first 3 days mean value (18,0 (17,0-20,0) pg/l), followed by decreasing to baseline mean value at 3 months time-point observation (to 18,0 (16,5-22,0) pg/l). Serum mean levels of IL-6 were unchanged during the whole observation period regardless of PSF presence (absence) and regardless of PSF clinical course as well. Conclusions 1. In PSF patients the time patterns of CRP reduction during the first months after ACE onset are much less synchronized with PSF duration. 2. In PSF patients, an increase of IL-1β level during acute ACE period is associated with prolongation of PSF duration at least till recovery ACE period. 3. PSF that first appeared during recovery ACE period is not associated with an increase in the blood level of any systemic inflammatory marker

Tags:

stroke, fatigue, intensity, interleukin, C-reactive protein.

Bibliography:

  1.  Joo H, George MG, Fang J, Wang G. A literature review of indirect costs associated with stroke. J Stroke Cerebrovasc Dis. 2014;23:1753-63.
  2.  Kim JS. Post-stroke mood and emotional disturbances: pharmacological therapy based on mechanisms. Journal of stroke. 2016;18(3):244-55.
  3.  De Groot MH, Phillips SJ, Eskes GA. Fatigue associated with stroke and other neurologic conditions: Implications for stroke rehabilitation. Arch Phys Med Rehabil. 2003;84:1714-20.
  4. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Heart disease and stroke statistics – 2014 update: a report from the American Heart Association. Circulation. 2014;129:28-292.
  5.  Haacke C, Althaus A, Spottke A, Siebert U, Back T, Dodel R. Long-term outcome after stroke: evaluating health-related quality of life using utility measurements. Stroke. 2006;37:193-8.
  6. Delva M, Lytvynenko N, Delva I. Factors associated with the time-based phenomenology of post-stroke fatigue over the first year after stroke occurrence. Georgian medical news. 2018;6(279):92-7.
  7. Chen K, Marsh ЕВ. Chronic post-stroke fatigue: It may no longer be about the stroke itself. Clinical neurology and neurosurgery. 2018;174:192-7.
  8.  Wu S, Mead G, Macleod M, Chalder T. Model of understanding fatigue after stroke. Stroke. 2015;46:893-8.
  9.  McKechnie F, Lewis S, Mead G. A pilot observational study of the association between fatigue after stroke and C-reactive protein. The journal of the Royal College of Physicians of Edinburgh. 2010;40(1):9-12.
  10. Wu S, Duncan F, Anderson NH, Kuppuswamy A, Macloed MR, Mead GE. Exploratory cohort study of associations between serum C-reactive protein and fatigue after stroke. PloS one. 2015;10(11):e0143784.
  11. Ormstad H, Aass HC, Amthor KF, Lund-Sorensen N, Sandvik L. Serum cytokine and glucose levels as predictors of poststroke fatigue in acute ischemic stroke patients. J Neurol. 2011;258:670-6.
  12. Ormstad H, Aass HC, Amthor KF, Lund-Sorensen N, Sandvik L. Serum levels of cytokines, glucose, and hemoglobin as possible predictors of poststroke depression, and association with poststroke fatigue. Int J Neurosc. 2012;122:682-90.
  13.  Becker KJ. Inflammation and the silent sequelae of stroke. Neurotherapeutics. 2016;13(4):801-10.
  14.  Michielsen HJ, De Vries J, Van Heck GL. Psychometric qualities of a brief self-rated fatigue measure: The Fatigue Assessment Scale (FAS). J Psychosom Res. 2003;54:345-52.
  15. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46-56. DOI: 10.1038/nrn2297
  16.  Miller AH, Haroon E, Raison CL, Felger JC. Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress Anxiety. 2013;30(4):297-306. DOI: 10.1002/da.22084
  17. Moron JA, Zakharova I, Ferrer JV, Merrill GA, Hope B, Lafer EM, et al. Mitogen-activated protein kinase regulates dopamine transporter surface expression and dopamine transport capacity. J Neurosci. 2003;23(24):8480-8.
  18.  Malynn S, Campos-Torres A, Moynagh P, Haase J. The pro-inflammatory cytokine TNF-alpha regulates the activity and expression of the serotonin transporter (SERT) in astrocytes. Neurochem Res. 2013;38(4):694-704. DOI: 10.1007/s11064-012-0967-y
  19.  Ronnback L, Hansson E. On the potential role of glutamate transport in mental fatigue. J Neuroinflammation. 2004;1:22. DOI: 10.1186/1742- 2094-1-22
  20. Syed AB, Castell LM, Ng A, Winward C, Rothwell PM. Plasma glutamate levels predict fatigue after TIA and minor stroke. Cerebrovasc Dis. 2007;23:117.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 1 Part 2 (149), 2019 year, 130-134 pages, index UDK 616.831-005.1-002-06-07

DOI: