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RR MULTIPL SKLEROZLU BİREYLERDE NÖROVASKÜLER ÜNİTE BİOMARKERLARI İLE KLİNİK PROGRESYONU DEĞERLENDİREN DEĞİŞKENLER ARASINDAKİ İLİŞKİNİN İNCELENMESİ

Yıl 2025, Cilt: 10 Sayı: 2, 13 - 26, 31.08.2025
https://doi.org/10.52881/gsbdergi.1762684

Öz

Giriş: Multipl Skleroz, inflamasyon, demiyelinizasyon, akson hasarı ile karakterize otoimmün nörodejeneratif bir hastalıktır.
Amaç: Bu çalışma RR MS’li bireylerde nörovasküler ünite işleyişini değerlendiren biomarkerlar ile klinikte progresyon değerlendirmeleri için kullanılan fiziksel parametreler arasında olan ilişkiyi incelemek amacıyla tasarlanmıştır.
Yöntem: Çalışmaya kesin MS tanısı almış olan ve dahil edilme kriterlerini sağlayan 30 RRMS hastası dahil edilmiştir. Hastalara başlangıçta SMMT uygulanarak 24 puan ve üzeri alan hastalara demografik veri formu ve klinikte MS progresyonunu değerlendiren EDSS skalası, 6 Dakika yürüme testi, Zamanlı Kalk Yürü Testi ve 9 Delikli Peg Testi uygulanmıştır. Sonrasında hastalardan alınan kan örnekleriyle nörovasküler ünite fonksiyonunu değerlendiren GFAP, VEGF ve NfL biomarkerlarının ELİSA analizleri yapıldı.
Bulgular: Serum NfL düzeyi ile "son atak üzerinden geçen süre" değişkeni arasında pozitif yönde anlamlı ilişki saptandı (rho=0,366, p=0,047). Serum NfL, serum VEGF-a ve serum GFAP düzeyleri ile EDSS, DDPT (Dominant ve Non-Dominant), ZKYT ve 6DYT skorları arasında anlamlı bir ilişkisi olmadığı saptandı (p>0,05).
Sonuç: Sonuçlar serum VEGF-a, GFAP ve serum NfL seviyelerinin MS’de nörovasküler ünite disfonksiyonu ile karakterize hastalık progresyonunu belirleyen biomarkerlar olmayabileceğini ancak serum NfL’nin uzun dönem progresyonu ve Sekonder Progresif MS’e geçişi değerlendirmede önemli bir belirteç olabileceğini göstermektedir.

Kaynakça

  • 1. Paul A, Comabella M, Gandhi R. Biomarkers in multiple sclerosis. Cold Spring Harbor Perspectives in Medicine. 2019;9(3):a029058.
  • 2. Zéphir H. Progress in understanding the pathophysiology of multiple sclerosis. Revue Neurologique. 2018;174(6):358-63.
  • 3. Lassmann H. Multiple sclerosis pathology. Cold Spring Harbor Perspectives in Medicine. 2018;8(3):a028936.
  • 4. Brown LS, Foster CG, Courtney JM, King NE, Howells DW, Sutherland BA. Pericytes and neurovascular function in the healthy and diseased brain. Frontiers in Cellular Neuroscience. 2019;13:282.
  • 5. Benarroch E. What are the roles of pericytes in the neurovascular unit and its disorders?. Neurology. 2023;100(20):970-7.
  • 6. Schreiner TG, Romanescu C, Popescu BO. The blood–brain barrier—a key player in multiple sclerosis disease mechanisms. Biomolecules. 2022;12(4):538.
  • 7. Cashion JM, Young KM, Sutherland BA. How does neurovascular unit dysfunction contribute to multiple sclerosis?. Neurobiology of Disease. 2023;178:106028.
  • 8. Yang J, Hamade M, Wu Q, Wang Q, Axtell R, Giri S, et al. Current and future biomarkers in multiple sclerosis. International Journal of Molecular Sciences. 2022;23(11):5877.
  • 9. Arneth B, Kraus J. Laboratory biomarkers of multiple sclerosis (MS). Clinical Biochemistry. 2022;99:1-8.
  • 10. Barro C, Healy BC, Liu Y, Saxena S, Paul A, Polgar-Turcsanyi M, et al. Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis. Neurology: Neuroimmunology & Neuroinflammation. 2022;10(1):e200052.
  • 11. Amini Harandi A, Siavoshi F, Shirzadeh Barough S, Amini Harandi A, Pakdaman H, Sahraian MA, et al. Vascular endothelial growth factor as a predictive and prognostic biomarker for multiple sclerosis. Neuroimmunomodulation. 2022;29(4):476-85.
  • 12. Hansra GK, Jayasena T, Hosoki S, Poljak A, Lam BCP, Rust R, et al. Blood biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: a systematic review and meta-analysis. Cerebral Circulation - Cognition and Behavior. 2024;100216.
  • 13. Gong Y, Wu M, Huang Y, He X, Yuan J, Dang B. Research developments in the neurovascular unit and the blood brain barrier. Biomedical Reports. 2025;22(5):88.
  • 14. Moon S, Chang MS, Koh SH, Choi YK. Repair mechanisms of the neurovascular unit after ischemic stroke with a focus on VEGF. International Journal of Molecular Sciences. 2021;22(16):8543.
  • 15. Pekny M, Wilhelmsson U, Stokowska A, Tatlisumak T, Jood K, Pekna M. Neurofilament light chain (NfL) in blood—a biomarker predicting unfavourable outcome in the acute phase and improvement in the late phase after stroke. Cells. 2021;10(6):1537.
  • 16. Uzuner GT, Uzuner N. Neurovascular coupling in patients with relapsing-remitting multiple sclerosis. Clinical Neurology and Neurosurgery. 2016;146:24-8.
  • 17. Cashion JM, Young KM, Sutherland BA. How does neurovascular unit dysfunction contribute to multiple sclerosis?. Neurobiology of Disease. 2023;178:106028.
  • 18. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-54.
  • 19. Güngen C, Ertan T, Eker E, Yaşar R, Engin F. Standardize mini mental test’in Türk toplumunda hafif demans tanısında geçerlik ve güvenilirliği. Türk Psikiyatri Dergisi. 2002;13(4):273-81.
  • 20. Baert I, Freeman J, Smedal T, Dalgas U, et al. Responsiveness and clinically meaningful improvement, according to disability level, of five walking measures after rehabilitation in multiple sclerosis: a European multicenter study. Neurorehabilitation and Neural Repair. 2014;28(7):621-31.
  • 21. Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, et al. The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis. Multiple Sclerosis Journal. 2017;23(5):711-20.
  • 22. Kalron A, Dolev M, Givon U. Further construct validity of the Timed Up-and-Go Test as a measure of ambulation in multiple sclerosis patients. European Journal of Physical and Rehabilitation Medicine. 2017;53(6):841-7.
  • 23. Barton B, Peat J. Medical statistics: a guide to SPSS, data analysis and critical appraisal. Chichester: John Wiley & Sons. 2014.
  • 24. Field A. Discovering statistics using IBM SPSS statistics. London: SAGE Publications Limited. 2024.
  • 25. Charcot J. Histologie de la sclerose en plaques. Gazette Hôpitaux. 1868;41:554.
  • 26. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. New England Journal of Medicine. 1998;338(5):278-85.
  • 27. Adams CWM, Poston RN, Buk SJ, Sidhu YS, Vipond H. Inflammatory vasculitis in multiple sclerosis. Journal of the Neurological Sciences. 1985;69(3):269-83.
  • 28. Trotter JL, Wegescheide CL, Garvey WF, Tourtellotte WW. Studies of myelin proteins in multiple sclerosis brain tissue. Neurochemical Research. 1984;9(1):147-52.
  • 29. Traugott U, Reinherz EL, Raine CS. Multiple sclerosis: distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages. Journal of Neuroimmunology. 1983;4(3):201-21.
  • 30. Law M, Saindane AM, Ge Y, Babb JS, Johnson G, Mannon LJ, et al. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004;231(3):645-52.
  • 31. Filippi M, Campi A, Dousset V, et al. A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis. Neurology. 1995;45(3):478-82.
  • 32. Loevner LA, Grossman RI, Cohen JA, Lexa FJ, Kessler D, Kolson DL. Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements. Radiology. 1995;196(3):511-5.
  • 33. Ge Y, Grossman RI, Udupa JK, Babb JS, Mannon LJ, McGowan JC. Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis. Journal of Computer Assisted Tomography. 2002;26(1):62-8.
  • 34. Haacke EM, Ge Y, Sethi SK, Buch S, Zamboni P. An overview of venous abnormalities related to the development of lesions in multiple sclerosis. Frontiers in Neurology. 2021;12:561458.
  • 35. Filippi M, Preziosa P, Banwell BL, Barkhof F, Ciccarelli O, De Stefano N, et al. Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines. Brain. 2019;142(7):1858-75.
  • 36. El-Taibany AA, Heydarian P, Porada DA, Seeds MC, Atala A. Multiple sclerosis: etiology in the context of neurovascular unit and immune system involvement and advancements with in vitro blood–brain barrier models. Frontiers in Immunology. 2025;16:1595276.
  • 37. Balasa R, Barcutean L, Mosora O, Manu D. Reviewing the significance of blood–brain barrier disruption in multiple sclerosis pathology and treatment. International Journal of Molecular Sciences. 2021;22(16):8370.
  • 38. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews. 2004;25(4):581-611.
  • 39. Amini Harandi A, Siavoshi F, Shirzadeh Barough S, Amini Harandi A, Pakdaman H, Sahraian MA, et al. Vascular endothelial growth factor as a predictive and prognostic biomarker for multiple sclerosis. Neuroimmunomodulation. 2022;29(4):476-85.
  • 40. Kouchaki E, Shahreza BO, Faraji S, Nikoueinejad H, Sehat M. The association between vascular endothelial growth factor-related factors with severity of multiple sclerosis. Iranian Journal of Allergy, Asthma and Immunology. 2016;15(3):204-11.
  • 41. Sanchez JD, Martirosian RA, Mun KT, Chong DS, Llorente IL, Uphaus T, et al. Temporal patterning of neurofilament light as a blood-based biomarker for stroke: a systematic review and meta-analysis. Frontiers in Neurology. 2022;13:841898.
  • 42. Hansra GK, Jayasena T, Hosoki S, Poljak A, Lam BCP, Rust R, et al. Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: a systematic review and meta-analysis. Cerebral Circulation - Cognition and Behavior. 2024;6:100216.
  • 43. Kempuraj D, Dourvetakis KD, Cohen J, Valladares DS, Joshi RS, Kothuru SP, et al. Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders. Frontiers in Cellular Neuroscience. 2024;18:1491952.
  • 44. Uphaus T, Steffen F, Muthuraman M, Ripfel N, Fleischer V, Groppa S, et al. NfL predicts relapse-free progression in a longitudinal multiple sclerosis cohort study. EBioMedicine. 2021;72:103590.
  • 45. Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, et al. Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain. 2018;141(8):2382-91.
  • 46. Dimitriou NG, Meuth SG, Martinez-Lapiscina EH, Albrecht P, Menge T. Treatment of patients with multiple sclerosis transitioning between relapsing and progressive disease. CNS Drugs. 2023;37(1):69-92.
  • 47. Healy BC, Zurawski J, Chitnis T, Weiner HL, Glanz BI. Patient-reported outcomes associated with transition to secondary progressive multiple sclerosis. Quality of Life Research. 2022;31(6):1799-807.
  • 48. Thebault S, Abdoli M, Fereshtehnejad SM, Tessier D, Tabard-Cossa V, Freedman MS. Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis. Scientific Reports. 2020;10(1):10381.
  • 49. Mir IN, Chalak LF. Serum biomarkers to evaluate the integrity of the neurovascular unit. Early Human Development. 2014;90(10):707-11.
  • 50. Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. Journal of Neurotrauma. 2004;21(11):1553-61.
  • 51. Martínez MAM, Olsson B, Bau L, Matas E, Calvo ÁC, Andreasson U, et al. Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis. Multiple Sclerosis Journal. 2015;21(5):550-61.
  • 52. Kassubek R, Gorges M, Schocke M, Hagenston VA, Huss A, Ludolph AC, et al. GFAP in early multiple sclerosis: A biomarker for inflammation. Neuroscience Letters. 2017;657:166-70.
  • 53. Abdelhak A, Huss A, Kassubek J, Tumani H, Otto M. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Scientific Reports. 2018;8(1):14798.
  • 54. Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. The American Journal of Occupational Therapy. 1985;39(6):386-91.
  • 55. Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, et al. The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis. Multiple Sclerosis Journal. 2017;23(5):711-20.
  • 56. Lamers I, Feys P. Assessing upper limb function in multiple sclerosis. Multiple Sclerosis Journal. 2014;20(7):775-84.
  • 57. Sebastião E, Sandroff BM, Learmonth YC, Motl RW. Validity of the timed up and go test as a measure of functional mobility in persons with multiple sclerosis. Archives of Physical Medicine and Rehabilitation. 2016;97(7):1072-7.
  • 58. Nilsagard Y, Lundholm C, Gunnarsson LG, Denison E. Clinical relevance using timed walk tests and ‘timed up and go’ testing in persons with multiple sclerosis. Physiotherapy Research International. 2007;12(2):105-14.

INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS

Yıl 2025, Cilt: 10 Sayı: 2, 13 - 26, 31.08.2025
https://doi.org/10.52881/gsbdergi.1762684

Öz

Objective: Multiple sclerosis is an autoimmune neurodegenerative disease characterised by inflammation, demyelination and axonal damage. The present study was designed to examine the relationship between biomarkers assessing Neurovascular Unit functioning in individuals with RR MS and physical parameters used for progression assessment in the clinic.
Methods: Thirty RRMS patients who had a definitive diagnosis of MS and met the inclusion criteria were included in the study. Initially, the SMMT was administered to patients who scored 24 or higher. These patients completed a demographic data form and clinically assessed MS progression using the EDSS scale, the 6-Minute Walk Test, the Timed Up and Go Test, and the 9-Hole Peg Test. Blood samples were then collected for ELISA analysis of GFAP, VEGF, and NfL biomarkers, which assess Neurovascular Unit function.
Results: A positive and significant relationship was detected between serum NfL level and the “time since last attack” variable (rho=0.366, p=0.047). No significant relationship was detected between serum NfL, serum VEGF-a, and serum GFAP levels and EDSS, 9DPT (Dominant and Non-Dominant), TUG, and 6MWT scores (p>0.05).
Conclusions: The results suggest that serum VEGF-a, GFAP, and serum NfL levels may not be biomarkers for disease progression characterized by Neurovascular Unit dysfunction in MS, but serum NfL may be an important marker for assessing long-term progression and transition to Secondary Progressive MS.

Etik Beyan

For the implementation of the study, approval was obtained from the Lokman Hekim University Scientific Research Ethics Committee (Number: 2024313, dated 31.01.2025) and written permission was obtained from the relevant institution where the research was conducted. Written informed consent was obtained from all participants prior to the commencement of the study.

Destekleyen Kurum

The study did not receive any support from any funder.

Kaynakça

  • 1. Paul A, Comabella M, Gandhi R. Biomarkers in multiple sclerosis. Cold Spring Harbor Perspectives in Medicine. 2019;9(3):a029058.
  • 2. Zéphir H. Progress in understanding the pathophysiology of multiple sclerosis. Revue Neurologique. 2018;174(6):358-63.
  • 3. Lassmann H. Multiple sclerosis pathology. Cold Spring Harbor Perspectives in Medicine. 2018;8(3):a028936.
  • 4. Brown LS, Foster CG, Courtney JM, King NE, Howells DW, Sutherland BA. Pericytes and neurovascular function in the healthy and diseased brain. Frontiers in Cellular Neuroscience. 2019;13:282.
  • 5. Benarroch E. What are the roles of pericytes in the neurovascular unit and its disorders?. Neurology. 2023;100(20):970-7.
  • 6. Schreiner TG, Romanescu C, Popescu BO. The blood–brain barrier—a key player in multiple sclerosis disease mechanisms. Biomolecules. 2022;12(4):538.
  • 7. Cashion JM, Young KM, Sutherland BA. How does neurovascular unit dysfunction contribute to multiple sclerosis?. Neurobiology of Disease. 2023;178:106028.
  • 8. Yang J, Hamade M, Wu Q, Wang Q, Axtell R, Giri S, et al. Current and future biomarkers in multiple sclerosis. International Journal of Molecular Sciences. 2022;23(11):5877.
  • 9. Arneth B, Kraus J. Laboratory biomarkers of multiple sclerosis (MS). Clinical Biochemistry. 2022;99:1-8.
  • 10. Barro C, Healy BC, Liu Y, Saxena S, Paul A, Polgar-Turcsanyi M, et al. Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis. Neurology: Neuroimmunology & Neuroinflammation. 2022;10(1):e200052.
  • 11. Amini Harandi A, Siavoshi F, Shirzadeh Barough S, Amini Harandi A, Pakdaman H, Sahraian MA, et al. Vascular endothelial growth factor as a predictive and prognostic biomarker for multiple sclerosis. Neuroimmunomodulation. 2022;29(4):476-85.
  • 12. Hansra GK, Jayasena T, Hosoki S, Poljak A, Lam BCP, Rust R, et al. Blood biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: a systematic review and meta-analysis. Cerebral Circulation - Cognition and Behavior. 2024;100216.
  • 13. Gong Y, Wu M, Huang Y, He X, Yuan J, Dang B. Research developments in the neurovascular unit and the blood brain barrier. Biomedical Reports. 2025;22(5):88.
  • 14. Moon S, Chang MS, Koh SH, Choi YK. Repair mechanisms of the neurovascular unit after ischemic stroke with a focus on VEGF. International Journal of Molecular Sciences. 2021;22(16):8543.
  • 15. Pekny M, Wilhelmsson U, Stokowska A, Tatlisumak T, Jood K, Pekna M. Neurofilament light chain (NfL) in blood—a biomarker predicting unfavourable outcome in the acute phase and improvement in the late phase after stroke. Cells. 2021;10(6):1537.
  • 16. Uzuner GT, Uzuner N. Neurovascular coupling in patients with relapsing-remitting multiple sclerosis. Clinical Neurology and Neurosurgery. 2016;146:24-8.
  • 17. Cashion JM, Young KM, Sutherland BA. How does neurovascular unit dysfunction contribute to multiple sclerosis?. Neurobiology of Disease. 2023;178:106028.
  • 18. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-54.
  • 19. Güngen C, Ertan T, Eker E, Yaşar R, Engin F. Standardize mini mental test’in Türk toplumunda hafif demans tanısında geçerlik ve güvenilirliği. Türk Psikiyatri Dergisi. 2002;13(4):273-81.
  • 20. Baert I, Freeman J, Smedal T, Dalgas U, et al. Responsiveness and clinically meaningful improvement, according to disability level, of five walking measures after rehabilitation in multiple sclerosis: a European multicenter study. Neurorehabilitation and Neural Repair. 2014;28(7):621-31.
  • 21. Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, et al. The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis. Multiple Sclerosis Journal. 2017;23(5):711-20.
  • 22. Kalron A, Dolev M, Givon U. Further construct validity of the Timed Up-and-Go Test as a measure of ambulation in multiple sclerosis patients. European Journal of Physical and Rehabilitation Medicine. 2017;53(6):841-7.
  • 23. Barton B, Peat J. Medical statistics: a guide to SPSS, data analysis and critical appraisal. Chichester: John Wiley & Sons. 2014.
  • 24. Field A. Discovering statistics using IBM SPSS statistics. London: SAGE Publications Limited. 2024.
  • 25. Charcot J. Histologie de la sclerose en plaques. Gazette Hôpitaux. 1868;41:554.
  • 26. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. New England Journal of Medicine. 1998;338(5):278-85.
  • 27. Adams CWM, Poston RN, Buk SJ, Sidhu YS, Vipond H. Inflammatory vasculitis in multiple sclerosis. Journal of the Neurological Sciences. 1985;69(3):269-83.
  • 28. Trotter JL, Wegescheide CL, Garvey WF, Tourtellotte WW. Studies of myelin proteins in multiple sclerosis brain tissue. Neurochemical Research. 1984;9(1):147-52.
  • 29. Traugott U, Reinherz EL, Raine CS. Multiple sclerosis: distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages. Journal of Neuroimmunology. 1983;4(3):201-21.
  • 30. Law M, Saindane AM, Ge Y, Babb JS, Johnson G, Mannon LJ, et al. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004;231(3):645-52.
  • 31. Filippi M, Campi A, Dousset V, et al. A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis. Neurology. 1995;45(3):478-82.
  • 32. Loevner LA, Grossman RI, Cohen JA, Lexa FJ, Kessler D, Kolson DL. Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements. Radiology. 1995;196(3):511-5.
  • 33. Ge Y, Grossman RI, Udupa JK, Babb JS, Mannon LJ, McGowan JC. Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis. Journal of Computer Assisted Tomography. 2002;26(1):62-8.
  • 34. Haacke EM, Ge Y, Sethi SK, Buch S, Zamboni P. An overview of venous abnormalities related to the development of lesions in multiple sclerosis. Frontiers in Neurology. 2021;12:561458.
  • 35. Filippi M, Preziosa P, Banwell BL, Barkhof F, Ciccarelli O, De Stefano N, et al. Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines. Brain. 2019;142(7):1858-75.
  • 36. El-Taibany AA, Heydarian P, Porada DA, Seeds MC, Atala A. Multiple sclerosis: etiology in the context of neurovascular unit and immune system involvement and advancements with in vitro blood–brain barrier models. Frontiers in Immunology. 2025;16:1595276.
  • 37. Balasa R, Barcutean L, Mosora O, Manu D. Reviewing the significance of blood–brain barrier disruption in multiple sclerosis pathology and treatment. International Journal of Molecular Sciences. 2021;22(16):8370.
  • 38. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews. 2004;25(4):581-611.
  • 39. Amini Harandi A, Siavoshi F, Shirzadeh Barough S, Amini Harandi A, Pakdaman H, Sahraian MA, et al. Vascular endothelial growth factor as a predictive and prognostic biomarker for multiple sclerosis. Neuroimmunomodulation. 2022;29(4):476-85.
  • 40. Kouchaki E, Shahreza BO, Faraji S, Nikoueinejad H, Sehat M. The association between vascular endothelial growth factor-related factors with severity of multiple sclerosis. Iranian Journal of Allergy, Asthma and Immunology. 2016;15(3):204-11.
  • 41. Sanchez JD, Martirosian RA, Mun KT, Chong DS, Llorente IL, Uphaus T, et al. Temporal patterning of neurofilament light as a blood-based biomarker for stroke: a systematic review and meta-analysis. Frontiers in Neurology. 2022;13:841898.
  • 42. Hansra GK, Jayasena T, Hosoki S, Poljak A, Lam BCP, Rust R, et al. Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: a systematic review and meta-analysis. Cerebral Circulation - Cognition and Behavior. 2024;6:100216.
  • 43. Kempuraj D, Dourvetakis KD, Cohen J, Valladares DS, Joshi RS, Kothuru SP, et al. Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders. Frontiers in Cellular Neuroscience. 2024;18:1491952.
  • 44. Uphaus T, Steffen F, Muthuraman M, Ripfel N, Fleischer V, Groppa S, et al. NfL predicts relapse-free progression in a longitudinal multiple sclerosis cohort study. EBioMedicine. 2021;72:103590.
  • 45. Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, et al. Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain. 2018;141(8):2382-91.
  • 46. Dimitriou NG, Meuth SG, Martinez-Lapiscina EH, Albrecht P, Menge T. Treatment of patients with multiple sclerosis transitioning between relapsing and progressive disease. CNS Drugs. 2023;37(1):69-92.
  • 47. Healy BC, Zurawski J, Chitnis T, Weiner HL, Glanz BI. Patient-reported outcomes associated with transition to secondary progressive multiple sclerosis. Quality of Life Research. 2022;31(6):1799-807.
  • 48. Thebault S, Abdoli M, Fereshtehnejad SM, Tessier D, Tabard-Cossa V, Freedman MS. Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis. Scientific Reports. 2020;10(1):10381.
  • 49. Mir IN, Chalak LF. Serum biomarkers to evaluate the integrity of the neurovascular unit. Early Human Development. 2014;90(10):707-11.
  • 50. Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. Journal of Neurotrauma. 2004;21(11):1553-61.
  • 51. Martínez MAM, Olsson B, Bau L, Matas E, Calvo ÁC, Andreasson U, et al. Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis. Multiple Sclerosis Journal. 2015;21(5):550-61.
  • 52. Kassubek R, Gorges M, Schocke M, Hagenston VA, Huss A, Ludolph AC, et al. GFAP in early multiple sclerosis: A biomarker for inflammation. Neuroscience Letters. 2017;657:166-70.
  • 53. Abdelhak A, Huss A, Kassubek J, Tumani H, Otto M. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Scientific Reports. 2018;8(1):14798.
  • 54. Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. The American Journal of Occupational Therapy. 1985;39(6):386-91.
  • 55. Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, et al. The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis. Multiple Sclerosis Journal. 2017;23(5):711-20.
  • 56. Lamers I, Feys P. Assessing upper limb function in multiple sclerosis. Multiple Sclerosis Journal. 2014;20(7):775-84.
  • 57. Sebastião E, Sandroff BM, Learmonth YC, Motl RW. Validity of the timed up and go test as a measure of functional mobility in persons with multiple sclerosis. Archives of Physical Medicine and Rehabilitation. 2016;97(7):1072-7.
  • 58. Nilsagard Y, Lundholm C, Gunnarsson LG, Denison E. Clinical relevance using timed walk tests and ‘timed up and go’ testing in persons with multiple sclerosis. Physiotherapy Research International. 2007;12(2):105-14.
Toplam 58 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Fizyoterapi
Bölüm Makaleler
Yazarlar

Elif Asan 0000-0002-5586-0716

Sebati Sinan Ürkmez 0000-0002-8821-1835

Zeynep İrem Akyol 0009-0004-6030-2382

Murat Terzi 0000-0002-3586-9115

Banu Ünver 0000-0001-9758-6607

Yayımlanma Tarihi 31 Ağustos 2025
Gönderilme Tarihi 12 Ağustos 2025
Kabul Tarihi 25 Ağustos 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 10 Sayı: 2

Kaynak Göster

APA Asan, E., Ürkmez, S. S., Akyol, Z. İ., … Terzi, M. (2025). INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS. Gazi Sağlık Bilimleri Dergisi, 10(2), 13-26. https://doi.org/10.52881/gsbdergi.1762684
AMA Asan E, Ürkmez SS, Akyol Zİ, Terzi M, Ünver B. INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS. Gazi Sağlık Bil. Ağustos 2025;10(2):13-26. doi:10.52881/gsbdergi.1762684
Chicago Asan, Elif, Sebati Sinan Ürkmez, Zeynep İrem Akyol, Murat Terzi, ve Banu Ünver. “INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS”. Gazi Sağlık Bilimleri Dergisi 10, sy. 2 (Ağustos 2025): 13-26. https://doi.org/10.52881/gsbdergi.1762684.
EndNote Asan E, Ürkmez SS, Akyol Zİ, Terzi M, Ünver B (01 Ağustos 2025) INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS. Gazi Sağlık Bilimleri Dergisi 10 2 13–26.
IEEE E. Asan, S. S. Ürkmez, Z. İ. Akyol, M. Terzi, ve B. Ünver, “INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS”, Gazi Sağlık Bil, c. 10, sy. 2, ss. 13–26, 2025, doi: 10.52881/gsbdergi.1762684.
ISNAD Asan, Elif vd. “INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS”. Gazi Sağlık Bilimleri Dergisi 10/2 (Ağustos2025), 13-26. https://doi.org/10.52881/gsbdergi.1762684.
JAMA Asan E, Ürkmez SS, Akyol Zİ, Terzi M, Ünver B. INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS. Gazi Sağlık Bil. 2025;10:13–26.
MLA Asan, Elif vd. “INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS”. Gazi Sağlık Bilimleri Dergisi, c. 10, sy. 2, 2025, ss. 13-26, doi:10.52881/gsbdergi.1762684.
Vancouver Asan E, Ürkmez SS, Akyol Zİ, Terzi M, Ünver B. INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUROVASCULAR UNIT BIOMARKERS AND VARIABLES ASSESSING CLINICAL PROGRESSION IN INDIVIDUALS WITH RR MULTIPLE SCLEROSIS. Gazi Sağlık Bil. 2025;10(2):13-26.