15 Natural History and Management Options of Chronic Subdural Hematoma
Dana C. Holl, Angelos G. Kolias, Ruben Dammers, and Ivan Timofeev
Abstract
Keywords: chronic subdural hematoma pathophysiology surgical, nonsurgical middle meningeal artery embolization
15.1 Introduction
Chronic subdural hematoma (CSDH) is an abnormal collection of blood, blood breakdown products, and cerebrospinal fluid in the subdural space. It is an increasingly common neurological condition among the elderly, with a preponderance among men (male-to-female ratio across all age groups of 2:1).1, 2, 3, 4, 5, 6, 7 Its incidence has increased over time from 1.7 to 31.2 per 100,000 persons per year (before 2000)7, 8, 9 to 20.6 to 79.6 per 100,000 persons per year (from 2000 onward).7, 10, 11, 12 With the growing aging population, availability of neuroimaging, and the mounting use of antiplatelet medication and anticoagulant, the incidence of CSDH is expected to increase.13, 14
Clinical manifestations of CSDH are variable and mainly caused by immediate intracranial compression through expansion of the hematoma. CSDH has an indolent course of disease progression with an average latent period of weeks or even months3, 15, 16 until patients present with slowly progressive symptoms, such as headache, behavioral disturbance (cognitive decline, acute confusion), gait disturbance and falls, limb weakness, drowsiness, or coma. Aphasia, collapse, seizure, incontinence, visual disturbance, and vomiting have also been reported.3, 5, 17, 18
The increasing incidence of CSDH underscores the importance of understanding the pathophysiology, natural history, and the available treatment options. Whereas treatment goals for CSDH are well established, several important aspects of its clinical management remain controversial. This chapter examines available literature on the natural history and treatment options for CSDH.
15.2 Selected Papers on the Natural History of Chronic Subdural Hematoma
●Edlmann E, Giorgi-Coll S, Whitfield PC, Carpenter KLH, Hutchinson PJ. Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy. J Neuroinflammation 2017;14(1):108
●Holl DC, Volovici V, Dirven CMF, et al; Dutch Chronic Subdural Hematoma Research Group (DSHR). Pathophysiology and nonsurgical treatment of chronic subdural hematoma: from past to present to future. World Neurosurg 2018;116:402–411.e2
15.3 Natural History
Studies looking at the natural history of CSDH are sparse and are predominantly of low level of evidence. The natural history of CSDH remains unclear and is only described in case reports or small case series.
A recent phase 2 placebo-controlled trial of atorvastatin as primary therapy enrolled patients with a CSDH and mild symptoms (90% had a Glasgow Coma Scale [GCS] of 15 and no neurological deficits) found that the rate of progression to surgery due to increased CSDH volume and/or neurological worsening was 23.5% in the control group (74% within the first month and 26% during months 2–4).21 It has to be noted that the baseline CSDH volume was 62 mL in this study, which is substantially less than the baseline CSDH volume in most surgical series. Without any treatment, few CSDHs have been reported to regress spontaneously, whereas 40% of all patients may eventually recover on medical management without surgical intervention. At least 20% of patients undergoing conservative management will experience clinical deterioration and require surgical intervention. However, it seems that there are no clear clinical or radiological signs indicating whether the CSDH will resolve spontaneously or not.
CSDH is often preceded by a minor head trauma, which can cause cleavage of the dural border cell layer (Fig. 15.1).18, 19, 20 This cell layer is a sublayer of the dura mater consisting of flattened fibroblasts with minimal extracellular collagen.22, 23, 24 Damage of the dural border cell layer leads to the formation of the subdural space with an external and an internal membrane, which develop within 1 and 3 weeks, respectively.25, 26 In contrast to the internal membrane, the external membrane is abundant with highly permeable capillaries, which leads to extravasation of vascular contents into the newly formed subdural space. In addition, the external membrane is thicker, with layers of active fibroblasts and collagen fibrils, a source of angiogenic and inflammatory mediators.18, 19, 20, 24 Once the dural border cell layer is damaged, CSF and/or small quantities of blood are interposed within this cell layer. This leads to a vicious cycle resulting in enlargement of the subdural space and the formation of a CSDH.19, 20
Three pathophysiological processes can be distinguished within the vicious CSDH cycle: inflammation, angiogenesis, and hyperfibrinolysis (Fig. 15.2).19, 20
Fig. 15.2 The pathophysiology of the chronic subdural hematoma (CSDH), characterized by inflammation, angiogenesis, and hyperfibrinolysis. This cycle perpetuates (CSF, cerebrospinal fluid; IL, interleukin; t-PA, tissue plasminogen activator; VEGF, vascular endothelial growth factor).
15.3.1 Inflammation
Damaged dural cells, fibroblasts, and endothelial cells release chemokines and cytokines, which activate a range of inflammatory cells, among which are neutrophils, eosinophils, lymphocytes, and macrophages.19, 20, 27, 28, 29, 30, 31, 32, 33 Cytokines, such as interleukin-6 (IL-6), IL-8, and the anti-inflammatory IL-10, are present in the CSDH at higher concentrations than in serum.34, 35, 36, 37, 38 CSDH is, therefore, a local inflammatory process, and does not inflict a systemic responses such as elevation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Inflammatory IL-6 is secreted within the subdural space by fibroblasts, monocytes, and endothelial cells39 in response to cell injury and hemorrhage.40, 41 It provides an acute response to inflammation with B and T cell differentiation, enhancement of leucocyte recruitment, and acute phase protein induction.39, 40 In addition, it increases platelet production and enlarges endothelial gap junctions with subsequent increased vascular permeability.42 Proinflammatory IL-8 attracts inflammatory cells, among which are neutrophils, to the inflammation site.43 IL-8 also acts as an angiogenic factor.38, 44 Anti-inflammatory IL-10 deactivates T cells, monocytes, and macrophages, and reduces proinflammatory cytokine production.45, 46
15.3.2 Angiogenesis
Vascular endothelial growth factor (VEGF) is one of the proangiogenic factors, which is found at significantly higher concentrations in the external membrane and in CSDH fluid compared to serum and cerebrospinal fluid.28, 29, 30, 47, 48, 49, 50 It has been suggested that the probability of CSDH recurrence is higher in patients with a strong VEGF expression in the external membrane.34 VEGF is produced by macrophages and vascular endothelial cells within the external membrane. This production is stimulated by prostaglandin E2 and by hypoxia-inducible factor 1, present in the external membrane. It activates several pathways51, 52, 53 that induce angiogenesis and increase vascular permeability. VEGF, in combination with angiopoietin 2, leads to the formation of immature capillaries.
15.3.3 Hyperfibrinolysis
Inflammation causes the release of tissue plasminogen activator (t-PA) from endothelial cells. The level of t-PA is significantly higher in CSDH fluid than in plasma.54 When relatively high concentrations of t-PA are found in the CSDH, the risk of recurrence is higher.55, 56 t-PA activates plasminogen, which is converted into plasmin. This causes degradation of coagulation factors V, VIII, and XI. Plasmin also breaks down fibrin clots into fibrinogen degradation products, among which is D-dimer, a platelet aggregation inhibitor.57, 58 The external membrane is also considered a source of thrombomodulin, which is found in high levels in CSDH fluid and enhances fibrinolysis.59 This thrombin receptor inhibits blood clotting by binding with thrombin and the activated protein C.37 Fibrin clots disintegrate and platelets cannot aggregate. This produces more cell injury and results in a higher inflammatory response and increased VEGF production.
The pathophysiological processes, in some patients, create a vicious cycle with the subdural collection gradually enlarging. High levels of inflammatory, angiogenic, and fibrinolytic factors are present in this newly formed subdural space. This can lead to gradual but progressive neurological deterioration in some patients. In order to break this pathological cycle, treatment is usually required. Surgical treatment is aimed at drainage and irrigation of the subdural space to decrease the mass effect and to reduce the levels of the inflammatory, angiogenic, and fibrinolytic factors. Nonsurgical treatments aim to control these processes pharmacologically. Conservative management with simple observation can also be used in some patients, especially those with very mild or no symptoms. However, to date it is unknown which factors contribute to the spontaneous resolution of CSDHs or may affect the balance between progression and spontaneous resolution. An increase or decrease in hematoma volume depends on the rebleed absorption rate and on the maturation and stabilization of the neomembrane.60
15.4 Selected Papers on the Management of Chronic Subdural Hematoma
●Kolias AG, Chari A, Santarius T, Hutchinson PJ. Chronic subdural haematoma: modern management and emerging therapies. Nat Rev Neurol 2014;10(10):570–578
●Almenawer SA, Farrokhyar F, Hong C, et al. Chronic subdural hematoma management: a systematic review and meta-analysis of 34,829 patients. Ann Surg 2014;259(3):449–457
●Brennan PM, Kolias AG, Joannides AJ, et al; British Neurosurgical Trainee Research Collaborative. The management and outcome for patients with chronic subdural hematoma: a prospective, multicenter, observational cohort study in the United Kingdom. J Neurosurg 2017;127(4):732–739
15.5 Treatment Options
Both surgical and nonsurgical approaches have been employed in the management of CSDH. Nevertheless, surgery remains the mainstay of management of patients with significant symptoms or enlarging collections. Further research on the pathophysiology and complexity of the CSDH is necessary to assess which treatment is most beneficial for individual patients. Several prospective trials have already been set up to provide class I evidence on the management of CSDH.63
In general, patients with significant symptoms or neurological deficits (e.g., hemiplegia) that can be attributed to a sizable CSDH will be offered surgical evacuation, if their premorbid status is reasonable. Patients with a poor premorbid status (e.g., dependent on others for activities of daily living and with several comorbidities) require careful consideration of the available options, including the option not to intervene. Patients with minimal symptoms or subtle deficits (e.g., slight pronator drift) can be managed expectantly or with pharmacotherapy (e.g., steroids).
15.5.1 Surgical
In general, three surgical techniques may be used to treat CSDH, namely, bur hole craniostomy (BHC), twist-drill craniostomy (TDC), and craniotomy.64 There are ongoing debates as to which of these techniques best influence on operative morbidity, mortality, recurrence rates, and overall outcome. The comparative effectiveness of these three surgical procedures remains poorly characterized and class I evidence is sparse. Retrospective studies are at high risk of bias, since treatment decisions are often based on the patients’ preoperative performance and on the individual preference of the treating physician.
Worldwide, BHC is the most employed procedure. Differences in effects on outcomes of BHC, TDC, and craniotomy are summarized in Table 15.1. In craniotomy, reported morbidity and mortality are higher compared to BHC and TDC; however, recurrence rates are substantially lower compared to TDC and BHC.61, 65, 66, 67 Craniotomy is mostly reserved for CSDH with large acute components and in CSDH with multiple membranes, or as a secondary treatment in recurrent CSDH and in subdural empyema after BHC or TDC. This might lead to higher morbidity and mortality numbers in this treatment group. Mini-craniotomy as primary surgical technique might, however, be an effective surgical technique for all types of CSDH and is the first-line option for some surgeons.68
Table 15.1 Surgical outcomes of CSDH
