Quantitative analysis of capsular microvasculature in relation to the thickness of chronic subdural hematoma

Boban Jelenković; Vesna Nikolov; Jovan Ilić; Marija Ilić; Aleksandar Marković; Hristina Jocić; Nikola Stojanović; Pavle Pešić

doi:10.2298/VSP241127010J

Boban Jelenković *University of Niš, Faculty of Medicine, Niš, Serbia; †University Clinical Center Niš, Department of Neurosurgery, Niš, Serbia
Vesna Nikolov *University of Niš, Faculty of Medicine, Niš, Serbia; †University Clinical Center Niš, Department of Neurosurgery, Niš, Serbia
Jovan Ilić University Clinical Center Niš, Department of Neurosurgery, Niš, Serbia
Marija Ilić University of Niš, Faculty of Medicine, Niš, Serbia
Aleksandar Marković University Clinical Center Niš, Department of Neurosurgery, Niš, Serbia
Hristina Jocić University Clinical Center Niš, Department of Neurosurgery, Niš, Serbia
Nikola Stojanović University Clinical Center Niš, Department of Neurosurgery, Niš, Serbia
Pavle Pešić University of Niš, Faculty of Medicine, Niš, Serbia

DOI: https://doi.org/10.2298/VSP241127010J

Keywords: blood vessels;, capillaries;, hematoma, subdural, chronic;, immunohistochemistry

Abstract

Background/Aim. Chronic subdural hematoma (CSDH) is an extra-axial, encapsulated, slow-growing hemorrhagic collection of blood, accompanied by local coagulopathy. This contributes to continuous re-bleeding from the newly formed capsule of hematoma, which leads to slow but progressive enlargement of the hematoma, with the potential to develop into a compressive intracranial lesion. The aim of this study was to investigate the relationship between the proliferation of sinusoid blood vessels and the growth and diameter of the CSDH. Methods. In this study, 33 cases of CSDH treated operatively were analyzed. A biopsy specimen (average size 3 × 3 mm) was obtained from the parietal capsule of the hematoma. The biopsied tissue samples were fixed in aqueous 4% buffered formaldehyde, routinely processed into paraffin-embedded slides, and immunohistochemically stained for the presence of the CD34 antigen. The profiles of microvascular bed blood vessels marked for CD34 were quantified, and the number of capillaries and sinusoids was expressed per one mm². Results. The variables age and number of blood vessels showed a statistically significant association with the increase in hematoma volume (β = 0.422, p = 0.007; β = 0.486, p = 0.022, respectively). Older patients had a higher risk of enlarged hematoma volume, as did patients with a larger number of sinusoidal blood vessels. Conclusion. The number of sinusoids in the parietal capsule of CSDH per surface unit of 1 mm² positively correlates with hematoma thickness, which emphasizes the importance of vascular theory in the development of a hematoma. Although CSDH is one of the most common neurosurgical diseases, its pathogenesis is still not fully understood. Further research in this field is necessary to develop potential new therapeutic options that would provide more comprehensive treatment modalities.

References

Yadav YR, Parihar V, Namdev H, Bajaj J. Chronic subdural hematoma. Asian J Neurosurg 2016; 11(4): 330–42. DOI: 10.4103/1793-5482.145102.

Uno M. Chronic subdural hematoma - evolution of etiology and surgical treatment. Neurol Med Chir (Tokyo) 2023; 63(1): 1–8. DOI: 10.2176/jns-nmc.2022-0207.

Catana D, Koziarz A, Cenic A, Nath S, Singh S, Almenawer S, et al. Subdural Hematoma Mimickers: A Systematic Review. World Neurosurg 2016; 93: 73–80. DOI: 10.1016/j.wneu.2016.05.084.

Mortazavi MM, Denning M, Yalcin B, Shoja MM, Loukas M, Tubbs RS. The intracranial bridging veins: a comprehensive re-view of their history, anatomy, histology, pathology, and neu-rosurgical implications. Childs Nerv Syst 2013; 29(7): 1073–8. DOI: 10.1007/s00381-013-2054-3.

Petrov A, Ivanov A, Dryagina N, Petrova A, Samochernykh, K, Rozhchenko L. Angiogenetic Factors in Chronic Subdural He-matoma Development. Diagnostics (Basel) 2022; 12(11): 2787. DOI: 10.3390/diagnostics12112787.

Levitt MR, Hirsch JA, Chen M. Middle meningeal artery embo-lization for chronic subdural hematoma: an effective treat-ment with a bright future. J Neurointerv Surg 2024; 16(4): 329–30. DOI: 10.1136/jnis-2024-021602.

Stubbs DJ, Davies BM, Edlmann E, Ansari A, Bashford TH, Braude P, et al. Clinical practice guidelines for the care of pa-tients with a chronic subdural haematoma: multidisciplinary recommendations from presentation to recovery. Br J Neuro-surg 2024; 1–10. DOI: 10.1080/02688697.2024.2413445.

Edlmann E, Giorgi-Coll S, Whitfield P, Carpenter KLH, Hutchinson PJ. Pathophysiology of chronic subdural haemato-ma: inflammation, angiogenesis and implications for pharma-cotherapy. J Neuroinflammation 2017; 14(1): 108. DOI: 10.1186/s12974-017-0881-y.

Thomas PAW, Marshman LAG, Rudd D, Moffat C, Mitchell PS. Growth and Resorption of Chronic Subdural Hematomas: Gardner, Weir, and the Osmotic Hypothesis Revisited. World Neurosurg 2019; 132: e202–7. DOI: 10.1016/j.wneu.2019.08.204.

Weigel R, Schilling L, Krauss JK. The pathophysiology of chron-ic subdural hematoma revisited: emphasis on aging processes as key factor. Geroscience 2022; 44(3): 1353–71. DOI: 10.1007/s11357-022-00570-y.

Holl DC, Volovici V, Dirven CMF, Peul WC, van Kooten F, Jellema K, et al. Pathophysiology and nonsurgical treatment of chronic subdural hematoma: from past to present to future. World Neurosurg 2018; 116: 402–11.e2. DOI: 10.1016/j.wneu.2018.05.037.

Ito H, Yamamoto S, Saito K, Ikeda K, Hisada K. Quantitative es-timation of hemorrhage in chronic subdural hematoma using the 51Cr erythrocyte labeling method. J Neurosurg 1987; 66(6): 862–4. DOI: 10.3171/jns.1987.66.6.0862.

Ito H, Saito K, Yamamoto S, Hasegawa T. Tissue-type plasmino-gen activator in the chronic subdural hematoma. Surg Neurol 1988; 30(3): 175–9. DOI: 10.1016/0090-3019(88)90269-8.

Ito H, Yamamoto S, Komai T, Mizukoshi H. Role of local hyper-fibrinolysis in the etiology of chronic subdural hematoma. J Neurosurg 1976; 45(1): 26–31. DOI: 10.3171/jns.1976.45.1.0026.

Ito H, Komai T, Yamamoto S. Fibrin and fibrinogen degradation products in chronic subdural hematoma. Neurol Med Chit (Tokyo) 1975; 15 pt 1: 51–5. DOI: 10.2176/nmc.15pt1.51.

Idowu OE, Oyeleke SO, Vitowanu JM. Impact of inflammatory cell ratio, biomarkers, activated partial thromboplastin time and prothrombin time on chronic subdural haematoma severi-ty and outcome. Eur J Trauma Emerg Surg 2022; 48(2): 1085–92. DOI: 10.1007/s00068-021-01665-5.

Nouri A, Gondar R, Schaller K, Meling T. Chronic Subdural Hematoma (cSDH): A review of the current state of the art. Brain Spine 2021; 1: 100300. DOI: 10.1016/j.bas.2021.100300.

El Rahal A, Beck J, Ahlborn P, Bernasconi C, Marbacher S, Wan-derer S, et al. Incidence, therapy, and outcome in the manage-ment of chronic subdural hematoma in Switzerland: a popula-tion-based multicenter cohort study. Front Neurol 2023; 14: 1206996. DOI: 10.3389/fneur.2023.1206996.

Suzuki K, Takano S, Nose T, Doi M, Ohashi N. Increased con-centration of vascular endothelial growth factor (VEGF) in chronic subdural hematoma. J Trauma 1999; 46(3): 532–3. DOI: 10.1097/00005373-199903000-00040.

Moskala M, Goscinski I, Kaluza J, Polak J, Krupa M, Adamek D, et al. Morphological aspects of the traumatic chronic subdural hematoma capsule: SEM studies. Microsc Microanal 2007; 13(3): 211–9. DOI: 10.1017/S1431927607070286.

Osuka K, Ohmichi Y, Ohmichi M, Honma S, Suzuki C, Aoyama M, et al. Angiogenesis in the outer membrane of chronic sub-dural hematomas through thrombin-cleaved osteopontin and the integrin α9 and integrin β1 signaling pathways. Biomedi-cines 2023; 11(5): 1440. DOI: 10.3390/biomedicines11051440.

Wei W, Yang T, Liu X, Li L, Fan Y. Gliomagenesis following chronic subdural hematoma: A case report. Exp Ther Med 2025; 30(1): 139. DOI: 10.3892/etm.2025.12889.

Kim H, Choi Y, Lee Y, Won JK, Lee SH, Suh M, et al. Neovas-cularization in outer membrane of chronic subdural hemato-ma: a rationale for middle meningeal artery embolization. J Korean Neurosurg Soc 2024; 67(2): 146–57. DOI: 10.3340/jkns.2023.0105.

Watanabe A, Tsutsumi S, Nonaka S, Ishii H. Microvascular pro-liferation in the clots: The key finding of acute subdural hema-toma transforming into chronic subdural hematoma? Surg Neurol Int 2021; 12: 601. DOI: 10.25259/SNI_1103_2021.