Original ArticleThe Pathogenesis of Chronic Subdural Hematomas: A Study on the Formation of Chronic Subdural Hematomas and Analysis of Computed Tomography Findings
Introduction
Chronic subdural hematoma (CSDH) is one of the most common neurosurgical disease of elderly patients. With advances in medical care, the elderly population will continue to increase and will remain more active, with therefore a potential increase in incidence of CSDHs. Currently, the overwhelming treatment modalities of fully developed CSDH are various forms of surgery, addressing its mass effect, but ideally, early medical treatment could prevent the formation of CSDH and avoid surgical procedures. The main obstacle to developing a more rational treatment of CSDH is our poor understanding of its origins, particularly the pathophysiology of its enlargement, despite the large body of literature dealing with this subject.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26
In 1826, Bayles ascribed the pathophysiology of CSDHs to “chronic rebleeding.” Virchow went on to further classify subdural hematomas (SDHs) in 1857 with the initial description of pachymeningitis hemorrhagica interna.3, 9
It was believed that CSDHs develop initially as acute SDHs after presumed trauma,21 but experience shows that in most instances small acute hematomas reabsorb spontaneously. Although recent research by Lee et al.,5, 6 supported by Nakaguchi et al.,14 suggests that traumatic subdural hygromas may be the major source of its transformations into CSDH, there are questions about the methodology of their studies and their conclusions, as pure subdural hygromas are quite rare. Lee5 in fact admits that the distinction between subdural hygromas and CSDH is difficult and often impossible.
Just as the several theories of the origin of the CSDH are not entirely satisfactory, so are the many theories of its enlargement. An early hypothesis by Gardner in 19323 was based on the hypothesis that SDHs grow in volume because blood components break down with time into smaller molecules, thereby increasing the osmotic pressure within the hematoma. This in turn pulls water into the hematoma “sac” from the cerebrospinal fluid (CSF), thereby causing a progressive expansion of the clot. Weir23 measured osmotic activity in the CSDH and serum and found them to be same and suggested that this theory alone cannot explain the enlargement, although its methodology is now being questioned.
Studies in which the authors used radioisotopes, however, found the presence of serum albumin in the subdural fluid, suggesting that plasma ultrafiltrate leaking through poorly developed microvasculature of the neomembranes may contribute to the CSDH enlargement.27 Another hypothesis suggests that the CSF leak into the hematoma is the primary cause of the enlargement through a disruption of the arachnoid membrane. Kristof et al.,4 using β-trace protein (βTP) as an indicator of CSF presence, reported that CSF was present in CSDH in 93% of their patients.
Whatever the initial step in development of CSDH, it currently is accepted that the next step is the migration of inflammatory cells derived from the dural border cells (DBCs) followed by fibroblasts along the dura and the development of outer membrane. In this membrane, there is a growth of fragile sinusoidal vessels with poorly developed endothelial cell junctions containing thrombomodulin, which is one of the factors that prevent the blood in the CSDH from clotting.13 These vessels are thought to be the source of repeated multifocal bleeding,11 which is accompanied by clotting prevention and hemolysis. This process currently is considered to be the main causative factors in the enlargement of CSDH.
We attempted to determine whether CSF leak into the hematoma in fact plays a significant role in the enlargement of CSDH and whether a different concentration of the products of hemolysis between CSDH fluid and serum may elucidate whether there is an active process versus plasma ultrafiltration. i.e., rebleeding/clot prevention. We further tested whether the chemical composition of the CSDH and/or CSF presence contribute the different appearance of CSDH on computed tomography (CT) scans. We analyzed the CSDH for the presence of CSF using beta-2 transferrin (β2T). Total protein, lactate dehydrogenase (LDH), total bilirubin, red blood cells (RBC), glucose, and K+ in both CSDH and serum also were measured.
Section snippets
Materials and Methods
After approval from institutional review board was obtained, samples were collected by a single investigator from consecutive patients older than the age of 18 years presenting for drainage of CSDH who were treated at Saint Barnabas Medical Center, a 597-bed regional hospital, from November 2006 to July 2008. Bilateral subdural collections, repeat drainage samples, and partial fluid analysis were included.
Each patient had at least one noncontrast head CT on admission and one more postsurgery.
Results
There were 41 patients with 58 total samples. The median age was 79 years, ranging from 41 to 96 years; 63% of the total patients were male. The results are shown in Table 1.
Twenty-seven samples were obtained from the right side, and 31 were obtained from the left side. Of these, 13 samples were bilateral. Four samples, 7% of total, were redrained. The results are shown in Table 2.
There were incomplete samples due to hemolysis of the sample or laboratory error. There are 8 patients with only
Discussion
Our result, based on the value of β2T, a transferrin variant that is restricted almost completely to the CSF, indicates that 24% of our patients had CSF in the sample of the CSDH. β2T is highly sensitive (94%–100%) and specific (98%–100%).28 These findings are highly statistically significant and confirm that CSF is present in approximately one quarter of CSDHs. This number, however, is substantially less than one reported by Kristof et al.,4 who found the presence of CSF in 93% of their
References (28)
The course of chronic subdural hematomas after burr-hole craniostomy with and without closed-system drainage
Neurosurg Clin N Am
(2000)- et al.
Rapid accurate and non-invasive detection of cerebrospinal fluid leakage using combined determination of beta-trace protein in secretion and serum
Clin Chim Acta
(2005) - et al.
MR characteristics of subdural hematomas and hygromas at 1.5T
AJR Am J Roentgenol
(1989) - et al.
Various magnetic resonance imaging patterns of chronic subdural hematoma: indicators of the pathogenesis?
Neurol Med Chir (Tokyo)
(2006) Traumatic subdural hematoma: with particular reference to the latent interval
Arch Neurol Psychiatry
(1932)- et al.
Cerebrospinal fluid leakage into the subdural space: possible influence on the pathogenesis and recurrence frequency of chronic subdural hematoma and subdural hygroma
J Neurosurg
(2008) The pathogenesis and clinical significance of traumatic subdural hygroma
Brain Inj
(1998)- et al.
Location of the traumatic subdural hygroma: role of gravity and cranial morphology
Brain Inj
(2000) - et al.
The computed tomographic attenuation and the age of subdural hematomas
J Korean Med Sci
(1997) - et al.
The fate of traumatic subdural hygroma in serial computed tomographic scans
J Korean Med Sci
(2000)
Origin of chronic subdural hematoma and relation to traumatic subdural lesions
Brain Inj
Chronic subdural hematomas: a review
J Neurosurg
Influence of neomembranous organization, cortical expansion and subdural pressure on the post-operative course of chronic subdural haematoma—an analysis of 201 cases
Acta Neurochir
Why do chronic subdural hematomas continue to grow slowly and not coagulate? Role of thrombomodulin in the mechanism
J Neurosurg
Cited by (20)
Nationwide trends in middle meningeal artery embolization for treatment of chronic subdural hematoma: A population-based analysis of utilization and short-term outcomes
2021, Journal of Clinical NeuroscienceCitation Excerpt :SDH is caused by tearing of bridging veins traversing the subdural space [22]. After SDH formation, a membrane develops around the hematoma through an inflammatory process which subsequently undergoes neovascularization, resulting in leaky and fragile microcapillaries, and ultimately leading to cSDH enlargement and recurrence [23–27]. Previously, the angiographic “wispiness” of distal MMA branches was reported to be associated with the neovascularization involved in cSDH formation [28].
Letter to the editor: Vascular endothelial growth factor in the pathogenesis of chronic spontaneous subdural hematoma
2021, Clinical Neurology and NeurosurgeryTreatment of Chronic Subdural Hematomas Utilizing Middle Meningeal Artery Embolization
2020, Journal of Radiology NursingCitation Excerpt :The hematoma is believed to form as a result of damage to bridging veins either by trauma or from chronic atrophy and stretching of the vessels in the elderly population (Soleman et al., 2017). The growth and formation of the hematoma then involves separation of the dural bilayer and dural boarder cells which triggers granulation tissue formation, macrophage deposition, and angiogenesis leading to the formation of a membrane around the hematoma (Haldrup et al., 2020; Jafari et al., 2017; Link et al., 2019; Srivatsan et al., 2019). The neovessels formed allow for continued microhemorrhages and recurrence of the hematoma (Jumah et al., 2020; Link et al., 2019; Soleman et al., 2017).
Embolization of the Middle meningeal artery in chronic subdural hematoma — A systematic review
2019, Clinical Neurology and NeurosurgeryCitation Excerpt :Based on the pathophysiology of cSDH, MMAE could be an interesting paradigm. The current model of SDH chronicization involves the formation of an inflammatory membrane lining the dura mater capable of both perpetuating the hematoma and of bleeding acutely [43–45]. The generation of such a membrane involves neovascularization, in which the vessels are derived from the dura mater and perfused mainly by distal branches of the MMA [8].
Middle Meningeal Artery Embolization Combined With Endoscopic Treatment for Chronic Subdural Hematoma
2023, Journal of Craniofacial Surgery
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.