Chronic subdural hemorrhage: from pathophysiology to treatment options
Article information
Abstract
Chronic subdural hematoma is defined as a predominantly hypodense or isodense crescentic collection along the cerebral convexity on cranial computed tomography, with ≥3 weeks onset. This paper summarizes the current knowledge of pathophysiology and treatment options including conservative and surgical treatment. Pharmacological therapy consists of steroids, statins, tranexamic acid, and antiepileptics. The surgical treatment of burr-hole craniostomy, twist-drill craniostomy, craniotomy/minicraniotomy, and middle-meningeal artery embolization are also covered.
Introduction
Subdural hemorrhage (SDH) is an accumulation of blood between arachnoid & inner dural layers of meninges [1]. According to their clinical onset, SDH can be classified into acute (<72 hours), subacute (72 hours to 3 weeks) & chronic (≥3 weeks) [2].
Chronic subdural hematoma (CSDH) is defined as a predominantly hypodense or isodense crescentic collection along the cerebral convexity on cranial computed tomography (CT) [1]. Intraoperatively, it can be defined as an SDH surrounded by a thin capsule (hematoma membrane) and consisting of dark reddish liquefied blood at operation [3]. It can be caused by traumatic stretching & tearing of cortical bridging veins that cross subdural space & drain into dura or dural sinus, coagulopathy, subdural dissection of parenchymal hematomas & rupture of vascular anomaly into subdural space [1,4].
Epidemiology
CSDH is a common neurosurgical disease among elderly, but can also occur in infants. It is associated with substantial morbidity and mortality. Multiple etiological concepts has been proposed, such as trauma, inflammation and aging [4–7]. Furthermore, several studies had been published regarding its incidence. In Awaji, Japan and it is reported an overall incidence of 13.1 per 43 100,000 persons per year from 1986 to 1988 [4]. In Finnish CSDH cohort study (1990–2015), the overall incidence of CSDH among 80 years and older doubled from 8.2 to 17.6/100,000/year [8]. In infants, it is 16.5 per 100.000 [9]. From 2005 to 2007, a national registry in Japan revealed an incidence rate of 20.6 per 100,000 per year. Among United States veteran population between 2000 and 2012, the incidence of CSDH is 79.4 per 100,000/year. Global population of people aged 80 and older is expected to be more than triple between 2015 and 2050 [10,11]. Consequently, there will be a growing burden related to CSDH.
Anatomical Considerations
The dura mater is separated from the arachnoid by a thin layer of dural border cells. The dural border cell layer contains flattened, elongated cells connected by desmosomes with amorphous extracellular matrix and limited extracellular fibers which makes this cell layer a natural cleavage plane easily separated. Walls of veins traversing from cortex to the dura (bridging veins of dura to venous sinuses) are as thin as 10 µm when passing through the dural border cell layer. These veins are predisposed to tearing when traversing from potentially mobile brain to the fixed points in dural sinuses (Fig. 1) [1,4].
Dural border cell layer SAS, subarachnoid space. Adapted from Kliot et al. Youmans & Winn neurological surgery. 8th ed. Elsevier; 2023. p. 360-67, with permission [4] and Valadka AB. Traumatic brain injury. In: Moore EE, Feliciano DV, Mattox KL, editors. Trauma. 8th ed. McGraw-Hill Education; 2017. p. 381-400, with permission [1].
Pathophysiology
CSDHs are encapsulated, flattened structures. It developed by proliferation from cells of the dura and probably of dural border cell layer with ingrowth of dural capillaries. It contains numerous thin-walled sinusoidal blood vessels, fibroblasts, mast cells, eosinophils, and myofibroblasts. The inner membrane is a thin (30 to 300 µm), relatively avascular layer of cells that adheres to the residual dural border cells and arachnoid cells. CSDHs also contain fluid ranging from yellow to dark brown [3,4,7].
In the past, pathophysiological concepts suggested that CSDH is secondary to degradation of subdural collections of blood and its products exerting merely a mass effect on the underlying brain. Development of CSDH also requires a predisposing factor of a shrinking volume within the cranial vault [5]. Nowadays, pathophysiologic cycle of CSDH formation and expansion involves traumatic and inflammatory components that promote formation of membranes with permeable neo-vessels, in which molecular & angiogenic factors involved (Fig. 2) [7,10,11].
Contemporary etiological concept of chronic subdural hematoma. (A) Anatomical schema of dural border cells. These cells exist between the arachnoid and dura mater. (B) After minor trauma, bleeding occurs from dural border cells. (C) After inflammatory reaction and additional minor trauma, the subdural space is noted to enlarge. (D) Blood leaks and inflammatory reactions are repeated; then, an outer membrane forms. Next, an inner membrane forms. Granulation and angiogenesis of the membrane gradually induce thickening of the dural border cell layer. (E) The outer membrane participates in the enlargement of the hematoma associated with various actions, and the inner membrane participates in liquefaction of the hematoma. These reactions lead to the enlargement of the hematoma and, ultimately, formation of the chronic subdural hematoma. Adapted from Uno. Neurol Med Chir (Tokyo) 2023;63:1–8, according to the Creative Commons license [7].
After initial development phase of an acute subdural hematoma, clotted blood can liquefy and cellular components of the hemorrhage can disintegrate, leaving serous fluid in the subdural space. This serous fluid is often intermixed with clotted blood. Its resolution relies on neuroparenchymal counterpressure. Reorganization and formation of vascular membranes that encapsulate the CSDH can further prevent reabsorption. Clotting cascade dysfunction can result in defective clot formation and hemorrhage recurrence, with elevated levels of tissue plasminogen activators which exacerbates this problem [12].
More specifically, subclinical traumatic injury can split open the dural border cell layer which leads to a reactive inflammatory cascade and the release of angiogenic factors leading to formation of an inflammatory membrane and fragile neo-vessels that cause continuous exudation of fluid and blood over time. As the hematoma expands, it raises intracranial pressure, and compresses nearby brain parenchyma, variable clinical manifestations may result, including headache, nausea or vomiting, mental status change, seizure, weakness, sensory disturbance, gait abnormality, and coma. CSDH has also been known as the ‘great immitator’ because of its heterogenous presentation [6,11].
Other theories why CSDHs can enlarge over time: (1) Self-perpetuating cycle of recurrent hemorrhage, fibrinolysis, inflammation, and angiogenesis. (i) Extravasated blood undergoes platelet activation, which causes the release of platelet-derived growth factor and clotting, which causes the release of thrombin and fibrinogen; (ii) Recurrent cycles of bleeding will start new cycles of clotting-fibrinolysis-inflammation-angiogenesis cycle that overlap with other ongoing phases; (iii) Hemolysis of blood will cause the cycle of recurrent CSDH. (2) Difference in osmolarity between CSF, blood and CSDH fluid cause the CSDH to enlarge by imbibing CSF. But this concept is not supported by studies [4].
Diagnosis
Mainstay in diagnosing CSDH is CT Scan. It is a rapid & cost-effective modality. It is well suited for identifying hematoma site, thickness, midline displacement and presence of subdural clots [6]. CSDH can be identified on CT scan as a crescent-shaped mass, and based on density, it can be classified as hyperdense (>60 Hounsfield unit [HU]), isodense (30–60 HU), or hypodense (8–30 HU) mass [4,7]. With time, the hematoma becomes less dense. It is due to hemoglobin in CSDH fluid. CSDH is often more hypodense in the early stage, isodense or of high density in the mature stage, of mixed density in the progressive stage, and of low density in the resolving phase (Fig. 3) [4,12].
Different chronic subdural hemorrhage on computed tomography scans. (A) Homogenous hypodense, (B) homogenous isodense, (C) trabeculated, (D) layering separated, (E) laminar, (F) layering gradated, Adapted from Kliot et al. Youmans & Winn neurological surgery. 8th ed. Elsevier; 2023. p. 360-67, with permission [4].
Based on its internal architecture and density, CSDHs can be classified into 4 types: (1) Homogeneous type was defined as a hematoma with homogeneous density (low–high=hypo, iso & hyperdense) [3]. (i) Outer and inner membranes develop around the subdural space. As the hematoma matures, blood vessels derived from the middle-meningeal artery (MMA) extend into hematoma membrane, causing vascular congestion. Arterial pressure stresses the walls of the sinusoidal microcapillaries, resulting in minor, but persistent, subdural bleeding episodes [3,4]; (ii) Risk for enlargement and recurrence is 10% to 15% [4]. (2) Laminar type was defined as a subtype of homogeneous type that had a thin high-density layer along inner membrane [3]. (i) High-density laminar structure running along the inner membrane is considered to consist of fresh blood from the hematoma membrane [3]; (ii) Higher risk for enlargement [4]. (3) Layered Separated type is a hematoma containing 2 components of different densities with a clear boundary (distinct boundary) lying between, where a lower density component located above a higher density component [3,6]. (i) As the hematoma matures, fibrinolysis occurs. Hematoma separates into 2 components, such that a thin component becomes mixed with a thick component of the liquefied hematoma and normal head motion cannot homogenize these components. It increases in volume and compress & congest surrounding brain [3]. (4) Layered Gradation type is a hematoma with indistinct boundary, in which the low and high density being mingled at the border, this was called the “gradation” type and was considered to be a subtype of the separated type. Mild head movement causes homogenization of hematoma. Therefore, the hematoma is not completely separated [3,6]. (5) Trabecular (multilocular) type is a hematoma with inhomogeneous contents and a high-density septum running between inner and outer membrane on a low-density to isodense (mixed density) background (high-density septa created by fibrosis) usually with low-intensity or isointense background [3]. (i) Interstitial hematoma matrix changes from an isodense to a low-density signal on CT scans, and on surgical inspection (from a dark reddish to xanthochromic translucent liquefied hematoma) which diminishes in volume over time; (ii) Low risk for growth and recurrence [4].
Treatment Options
Conservative
This treatment measures consist of observation period, medical management, intracranial pressure control, anticoagulation reversal & serial exams. Generally nonoperative treatment is offered to patients in whom operative risks believed to outweigh benefits of surgery, whom are asymptomatic with small collections at 1 end of spectrum, moribound with poor baseline function [4,11].
There are several medical therapies can be used for treatment of CSDH such as antiepileptic medications, steroids, statins, tranexamic acid & angiotensin-converting enzyme (ACE) inhibitors. (1) Antiepileptic medication (levetiracetam & valproic acid) has been shown not to significantly decrease incidence of seizures with a pooled risk ratio of 0.82 (P=0.79) in a systematic review & meta analysis,. The pooled incidence of seizures was 7.8% in patients who did not receive any antiepileptic drug (AED) as compared with 5.4% those who received AEDs. This may be due to etiology of seizure in CSDH is due to higher concentration of fibrin degradation products (which can irritate the brain parenchyma and lead to the formation of membranes) & cortical injury in surgery. So, it is only indiated if there is any significant behavioral/psychiatric issue [13]. (2) A 2-week course of dexamethasone (8 mg twice daily on days 1 to 3, then 6 mg twice daily on days 4 to 6, then 4 mg twice daily on days 7 to 9, then 2 mg twice daily on days 10 to 12, and then 2 mg once daily on days 13 and 14) in symptomatic CSDH can lower reoperative rate but worse functional outcome at 6 months. Efficacy of steroids is due to its influence in reducing inflammatory pathway in pathogenesis of CSDH [14]. (3) Atorvastatin (20 mg daily for 8 weeks) has been reported to be favoring clinical improvement. This is due to its antiinflammatory effects & facilitation of blood vessel repair by recruiting endothelial progenitor cells [15]. (4) Tranexamic acid (an anti-fibrinolytic agent, 750 mg/day until resolution) has the ability to halt fibrinolysis and the kinin-kallikrein inflammatory system, favoring hematoma resolution [16]. (5) ACE inhibitors have ability to induce induce bradykinin, leading to an increase in permeability of the highly cellular and vascular neomembranes. It is also known to have antiangiogenic effec via tempering of vascular endothelial growth factor expression [16,17].
Typically CSDH patients are often elderly with multiple comorbidities. So, during initial admission, efforts must be made to reverse coagulopathy & thrombopathy and managed in conjunction with other specialties. CHA2DS2-VAsC thromboembolism risk score and HAS-BLED bleeding risk score can be used as assessment tool for patients with other comorbidities of bleeding & thrombosis [4].
Surgical treatment
Surgical drainage is indicated in symptomatic radiologically confirmed CSDH. There are 3 primary surgical techniques utilized: twist-drill craniostomy (TDC) (<10 mm opening), burr-hole craniostomy (BHC) (10 to 30 mm opening) and Craniotomy. When considering which technique be used, take into account the frailty physiology, comorbidities & risk of recurrence.
TDC is indicated in predominantly hypodense collection with no membranes and unsuitable for general anesthesia, desirably for elderly with several medical comorbidities & provides relatively slow decompression, which will decrease incidence of complications (such as intraparenchymal hemorrhage). It may be performed at bedside on ward or neurocritical care unit. 2 or more twist-drill holes placed over maximal width of hematoma, dura & outer membrane pierced with spinal needle and drainage system (e.g., subdural irrigating, nonirrigating drains & hollow-screw system) are placed. Drains may be removed after approximately 48 hours. It has a morbidity rate of 24% and a complication rate of 9% [4,11].
BHC is indicated in symptomatic CSDH without multiple membranes or significant component to hematoma. It is usually performed with general anesthesia but can be performed under local anesthesia. 2 burr holes are placed over the maximum width of hematoma, roughly 7 cm apart. Usually 1 frontal & 1 parietal burr hole are made and just superior to superior temporal line, dura & outer membrane of CSDH incised & releasing hematoma fluid. Subdural space is then irrigated with saline until effluent runs clear (Jacques catheter may be used to augment thorough irrigation in remote areas from burr holes. It carries blind insertion risk). Thick wafer of absorbable sponge can be used to achieve hemostasis & improve seal then wound is closed. Drain (tube length at least 50 cm) can be inserted into subdural space via frontal burr hole (parietal hole is closed) and positioned below level of patient’s head and can be removed after 48 hours. Compared to 2 other techniques, BHC have the lowest complication rate (as low as 8%, higher if patient kept upright after surgery). BHC group showed significantly lower pooled failure & cure rates and a lower reoperation rate compared with the TDC group (12% vs. 28%) (Fig. 4) [4,6,11].
Chronic subdural hematoma surgical evacuation. (A) Burr-hole craniostomy with subdural drain, 2 burr holes created with a perforator. (B) Twist-drill craniostomy: single twist-drill hole created over thickest portion of haematoma with a minimally invasive hollow screw in situ. (C) Minicraniotomy with subdural drain. Adapted from Kolias et al. Nat Rev Neurol 2014;10:570–8, with permission [6].
Craniotomy (>6 cm opening) and minicraniotomy (<6 cm opening) are indicated with significant acute component, multiple membranes, encapsulated or recurrent CSDH. In this technique, general anesthesia must be used. After placing head on horsehoe headrest, head & shoulders tilted 45 degrees to contralateral side, aiming for frontal half of craniotomy to be in highest point of head. A free bone flap of varying sizes (usually >30 mm) is created over hematoma to provide maximal access. Dura & outer membrane opened & cavity is irrigated with saline. Soft silicone drain inserted subdurally & bone flap is replaced & secured. Drain is removed after 48 hours. In this technique, the mortality rate is 13,5%. Minicraniotomy is utilized in recurrent CSDH with extensive organization & membrane formation or primary evacuation of CSDH with significant acute component. This method is utilized as secondary prevention of recurrence after initial recurrence (Fig. 5) [4,7,11,18].
Procedure-specific complications include focal brain injury, postoperative acute subdural or intracranial hemorrhage, seizures, surgical site infection, subdural empyema, and tension pneumocephalus [4,6].
Recurrence rates in literature varies widely from 0% to 76% but only around 10% neccesitates reoperation when optimum techniques including subdural drains used. Factors associated with recurrence include bilateral CSDH, preoperative anticoagulant and/or antiplatelet medication, intraoperative visualization of poor brain reexpansion and thick membranes, and postoperative persistence of midline shift and intracranial air [6,11]. To lower this rate, further use of steroids or MMA embolization after surgery may be utilized.
Middle-meningeal artery embolization
This technique is utilized by neuro-endovascular means, targetting on major underlying pathophysiological mechanism sustaining CSDH: leakage of blood products & exudate from permeable vascular membrane. By de-vascularizing this membrane by embolization usually with polyvinyl alcohol, leakage can be minimized and facilitates effective reabsorbtion. Bright-Falx sign must be achieved after embolization to ensure success. Its failure is associated with blood supply in newly formed vessels due to inflammation (Fig. 6) [11,19].
Digital substraction angiography view of middle meningeal artery embolization & bright-falx sign by using the “sugar rush technique.” (A) Selective catheterization of posterior branch of the MMA (white arrow), the cast of substance injected extended beyond the midline (black arrows). (B) Post-embolization computed tomography depicted the spread of the cast to the internal membrane of the hematoma and “bright falx” sign. Adapted from Nakagawa et al. Neurol Med Chir (Tokyo) 2023;63:327–33, with Creative Commons Licence [19].
Postoperative Care
After surgery, bed rest is adviced to reduce recurrent rates by promoting brain expansion, early mobilization is thought to decrease medical complications associated with immobility, specifically venous thromboembolism and hospital-acquired infection. There is no difference in recurrent rates but increased medical complicated in delayed mobilization (after 3 days) compared with early mobilization (on 1st postoperative day) [6]. Patients with impaired mobility should receive physiotherapy assistance, thromboprophylaxis (thromboembolism deterrent stockings, low molecular weight heparin after drain removal) [11].
Patients can be discharged when mobile or returning to baseline function. Early postop CT scans are not performed unless clinically indicated (symptomatic) [4].
Conclusions
CSDH is a common neurosurgical problem in elderly. In the future, the burden of this disease will become heavier. Knowledge about pathophysiology of this disease is changing over time, and so do the modalities of treatment, with their own indications, advantages and disadvantages. Nowadays, BHC is the most common procedure performed because of its efficacy. MMA embolization has also play a part in reducing recurrence rate after surgery.
Notes
Conflict of Interest
No potential conflict of interest relevant to this article was reported.