Working Toward Rational and Evidence-Based Treatment of Chronic Subdural Hematoma
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17 Working Toward Rational and Evidence-Based Treatment of Chronic Subdural Hematoma Thomas Santarius, MD, PhD, Peter J. Kirkpatrick, FRCS (SN), FMedSci, Angelos G. Kolias, MSc, MRCS, and Peter J. Hutchinson, FRCS (SN), PhD Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions that can usually be treated with relatively simple and effective surgical procedures. It affects primarily the elderly, a rising population worldwide. Together with improved awareness among the medical profession and greater access to modern imaging facilities, the incidence of CSDH is set to rise significantly. Maximization of the efficiency of management of CSDH is therefore a priority. To this end, a review of the findings of clinical and laboratory research underpinning the basis of the modern management of CSDH has been carried out. This review focuses on the pathophysiology and briefly discusses the epidemiology, clinical presentation, and surgical treatments of CSDH, concluding that a one-for-all management strategy is not appropriate. Creating rational bases for the selection of an ideal treatment strategy for an individual patient should be the target. This can be achieved through better understanding of the nature of the condition through systematic basic science research, ascertaining the merits of different surgical techniques in well- designed and rigorously executed clinical trials, using advances in imaging techniques to classify CSDH (a subject not addressed here), and training in and ongoing refinement of clinical acumen and surgical skills of individual surgeons. C hronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions that can usually be treated with relatively simple and effective surgical proce- dures. However, its management is not always straightforward. The preferred surgical method continues to attract debate, and the time for an evidence-based approach is now overdue. CSDHs affect primarily the elderly. According to the 2001 Report of the US Census Bureau, the proportion of people $ 65 years of age is expected to double worldwide between 2000 and 2030. 1 A corresponding rise in the incidence of CSDH is expected, particularly with a more active aging population. Improved awareness among the medical profession, together with greater access to modern imaging facilities, has improved the detection of CSDH; hence, the neurosurgical burden from CSDH is set to increase significantly. Here, we review the findings and highlight the targets of clinical and laboratory research that underpin the basis of the modern management of CSDH. We focus on the pathophys- iology and briefly discuss surgical treatments (the latter was comprehensively reviewed by Weigel et al 2 ). The epidemiology and clinical presentation of CSDH are also included because they are important for understanding the nature of CSDH. ANATOMY: THE SUBDURAL SPACE CSDHs are found between the dura mater and the arachnoid. Under normal conditions, however, a space or cavity does not exist at the junction between the dura and the arachnoid. Instead, a layer of cells with unique morphological features and a propensity to shear open is found at this point (Figure 1). 3-6
This layer is called the dural border cell (DBC) layer.
5,6 It is characterized by a relative paucity of tight junctions and enlarged extracellular space containing nonfilamentous, amorphous material. This layer therefore lacks strength and can easily be dissected, for example, by a surgeon during the elevation of dura or blood from shearing of a vein traversing the DBC layer. 7 The veins are anchored firmly within the arachnoid and the dural layers but less so within the DBC layer. With increasing brain atrophy, the arachnoid is pulled toward the center, whereas the dura remains attached to the skull. The resultant force stretches the DBC layer and veins traversing through it. Only a minor additional force may be required to cause shearing of a vein and leakage of blood that will further dissect the DBC layer, creating a subdural cavity. Indeed, this has been observed in experimental models. 8 Similarly, a trau- matic tear of the arachnoid can cause a hygroma, which can later transform into a CSDH (see more below). PATHOPHYSIOLOGY Although it is likely that CSDHs were treated by ancient civilizations in many parts of the world, 9-13
the first medical description of CSDH is probably that of Johannes Wepfer 14 in
Ó 2010 by The Congress of Neurological Surgeons 0148-396X 112 Clinical Neurosurgery Volume 57, 2010 his Observationes Anatomicae published in 1675. Uncertain of its nature, Wepfer described the fluid found in one of his postmortem cases as ‘‘serum.’’ In his 1857 article ‘‘Das Ha¨matom der Dura mater,’’ Virchov called CSDH pachyme- ningitis haemorrhagica interna, recognizing both its in- flammatory and hemorrhagic elements. 15 In 1914, Trotter 16 suggested the role of trauma to the bridging veins in the pathogenesis of the subdural hemorrhagic cyst, and Yamashima and Friede 17 later demonstrated, using electron microscopic data, that human bridging veins have thin walls of variable thickness, circumferential arrangement of collagen fibers, and a lack of outer reinforcement by arachnoid trabecules, all likely contributory factors to the subdural portion of the vein being more fragile than its subarachnoid portion. Today, it is widely accepted that CSDHs are a result of the failure of acute subdural hematomas to heal. Indeed, trans- formation of acute subdural hematoma is observed by neuro- surgeons in daily practice, and it has been documented in patients followed up with serial computed tomography. 18 However, in some cases, CSDH seems to have developed from an initial subdural hygroma. 19-26 Some authors maintain that, in fact, the majority of CSDHs develop from subdural hygromas rather than acute subdural hematomas. 20 Park et al 25 studied 145 cases of post-traumatic subdural hygroma of whom 13 developed into CSDH. The proportion of CSDHs arising from hygromas was even higher (6 out of 24) in a series by Yamada et al. 27 Kristof et al 28 found b-trace protein in subdural fluid in 90% of CSDHs, and b-trace protein was predictive of recurrence. It is possible that leakage of cerebrospinal fluid into the CSDH, at least in some cases, may play a role in hematoma growth. Both blood and cerebrospinal fluid are likely to shear open the DBC layer and create a subdural collection. It is possible that hemorrhage from a blood vessel traversing the DBC occurs even in the case of hygroma as the primary FIGURE 1. Schematic represen- tation of the ultrastructure of the meninges (adapted from Haines et al 5
posed of fibroblasts and a large amount of collagen. The arach- noid barrier cells are supported by a basement membrane and bound together by numerous tight junctions (red diamonds). The dural border cell layer (light blue) is formed by flattened fibroblasts with no tight junc- tions and no intercellular colla- gen. It is therefore a relatively loose layer positioned between the firm dura matter and arach- noid. The subdural space is a potential space that can form within the dural border cell layer. FIGURE 2. Age distribution of chronic subdural hematoma of the cohort of patients published by Santarius et al. 88 q
113 Clinical Neurosurgery
Volume 57, 2010 Chronic Subdural Haematoma-Review pathology. As in other tissue injuries, this triggers a complex reparatory response that aims to heal the tissues. Whatever the primary insult, it triggers an early inflammatory reaction characterized by proliferation of the DBCs, formation of granulation tissue with collagen fibers, and deposition of macrophages. 6,29,30 New blood vessels form that supply cellular and noncellular components necessary for tissue remodeling and final healing. It is likely that such a process is successfully completed in many cases, especially in young and healthy patients with nonatrophic brain. 20,31-33 However, in a proportion of cases, the repair process fails to achieve healing, and CSDH ensues. The CSDH consists of a subdural fluid surrounded by a membrane arising within the DBC layer. 29,30 Its visceral part is adjacent to the arachnoid and is relatively thin and avascular. 29,30 The parietal membrane is composed of multilayered tiers and clusters of cells derived from the DBCs, transfixed by multiple capillaries, with collagen fibrils and elastic fibers between them (Capillaries and collagen fibrils are absent from the normal DBC layer). 29,30 What causes CSDH hematoma to enlarge? All surgeons have observed a great variety of subdural fluid types, ranging from bright red liquid through to thick engine oil to light, serous fluid. Similarly, some CSDHs contain a very think parietal membrane, whereas in others the membrane is hardly visible with a naked eye. Therefore, it is likely that multiple factors are responsible for the maintenance and enlargement of CSDH, the relative importance of which varies from case to case. In 1925, Putnam and Cushing 34 proposed rebleeding from thin-walled sinusoidal blood vessels in the outer neomembrane. Since then compelling evidence for repeated hemorrhages as an important cause of for CSDH enlargement has been accumulated. Ito et al 35 infused 50 CSDH patients with 51 Cr- labeled erythrocytes and studied their concentra- tion in a fluid obtained during craniotomy performed between 6 and 24 hours later. They estimated that the new hemorrhages accounted on average for 6.7% of the hematoma content. Similarly, in an experimental mouse model of CSDH, Aikawa et al
36 observed fresh hemorrhages surrounded by hemosid- erin-laden macrophages in the outer membrane. Friede and Schachenmayr 29 reported that the loose and irregular de- position of collagen and DBCs provides little mechanical support for the sprouting new capillaries, which are fragile and bleed easily. Yamashita et al 37 studied the ultrastructure of the microcapillaries using an electron microscope. They reported that the endothelial cells have numerous large gap junctions (6-8 mm) and the basement membrane is either thin or absent, rendering the capillaries fragile and susceptible to bleeding. Moreover, erythrocytes and plasma were observed in the gap junctions, providing direct evidence of blood leakage. Murakami et al 38 identified high levels of plasma soluble thrombomodulin in the subdural fluid, an indication of an ongoing injury to the sinusoidal capillaries, thus demonstrating another potential mechanism of rebleeding. Thrombomodulin itself can inhibit coagulation by forming a complex with thrombin and activating protein C 111
. Under normal circumstances, capillary leaks would be stopped with blood clots. However, subdural and the parietal membrane are awash with profibrinolytic and anticoagulation factors. Indeed, subdural fluid was shown to accelerate fibrinolysis, a finding consistent with the clinical observation of a liquid, nonclotting contents of CSDH. 39 High levels of tissue plasminogen activator were measured in the subdural fluid and parietal membrane. 8,40-44 This enhanced fibrinolytic activity is further documented by the high concentration of fibrin degradation products in both the subdural fluid and the parietal membrane. 43,45,46
Moreover, Katano et al 42 have found tissue plasminogen activator to be predictive of recurrence, and Rughani et al 47 reported a patient with plasminogen activator inhibitor type I deficiency whose recurrent CSDH healed only after a course of aminocaproic acid. Relative reduction in the concentration of the profibrinolytic agents in the subdural fluid has frequently been used to explain the highly effective therapeutic burr hole drainage. 33,40,48,49 In addition to coagulation factors, the role of inflamma- tory and growth factors in CSDH has been investigated. High concentrations of vascular endothelial growth factor (VEGF) were found in subdural fluid and high expression of the VEGF receptor subtype 1 (FLT1) in the cells of the parietal membrane. 50-52 Hohenstein et al 50 found a markedly higher level of VEGF mRNA expression in cells floating in the hematoma fluid compared with cells obtained from the outer membrane. Thus, the hematoma fluid itself appears to be a strong promoter of ongoing angiogenesis and hyperperme- ability in CSDH rather than a mere reflection of an abnormally high demand for healing-associated angiogenesis. VEGF is also known to increase the permeability of capillaries and thus contribute directly to the increase in the volume of CSDH. Weigel et al 53 analyzed 310 patients, 81 of whom were taking angiotensin-converting enzyme (ACE) as a treatment for hypertension. Hypothesizing that hyperangiogenesis plays an important role in the pathogenesis of CSDH, the authors studied retrospectively the recurrence rate of patients with and without concurrent treatment with ACE inhibitors, agents that had been shown to inhibit angiogenesis. 53 Indeed,
the recurrence rate was 5% in patients taking and 18% in those not taking ACE inhibitors (P = .003). Moreover, the VEGF content was significantly lower (P = .012) in the hematomas of patients taking than those not taking ACE inhibitors. High concentrations of various molecules known to play a role in inflammation such as platelet-activating factor, interleukin-6 and -8, and bradykinins have also been found in subdural fluid. 55-59
Because of the important role of both inflammation and angiogenesis in CSDH, corticosteroids have been proposed in the management of CSDH. Steroids inhibit 114
q 2010 The Congress of Neurological Surgeons Santarius et al Clinical Neurosurgery
Volume 57, 2010 tissue plasminogen activator activity 60 and interleukin-6 and -8, and VEGF expression can be inhibited with corticosteroids. 61-63
Despite the fact that corticosteroids are used to treat CSDH, especially if conservative management is adopted, surprisingly few systematic studies of their role in CSDH have been published. Glover and Labadie 64 have shown that cortico- steroids inhibit the growth CSDH membrane. Although the use of steroids in the management of CSDH has been reported. 65-71 treatment with steroids has never been compared in a meaning- ful way with no treatment (in the case of nonoperative management). Similarly, we are not aware of a study that provides useful guidance about the role of steroids in surgically treated CSDH. Thus far, the rationale for using steroids has largely been based on theory, and clearly, more research into their treatment of CSDH is warranted. A once popular explanation for the maintenance and growth of CSDH, the osmotic theory, introduced by Gardner 72 in 1932 and later modified by Zollinger and Gross, 73 was largely abandoned after Weir’s 74,75
1971 and 1980 publications. The osmotic theory was based on the premise that fluid is attracted into the subdural space along the osmotic gradient created by the breakdown of blood products of the acute hematoma. However, Weir 74 compared the osmolality of the subdural hematoma fluid, venous blood, and cerebrospinal fluid and found no significant difference between them. Weir 75 also
found no significant difference between oncotic pressures of the fluid from subdural hematoma and venous blood, whereas the oncotic pressure of subdural hygroma was significantly lower. Similarly, Markwalder et al 48 found that the concentration of proteins in CSDH fluid is similar to that of blood. Recently, Heula et al 76 and Sajanti and Majamaa 77 found very high concentrations of the propeptides of type I and type III protocollagens in the subdural fluid (relative to their concen- trations in serum), suggesting sustained collagen synthesis. These concentrations were similar to those observed in wound fluid during the first few days after a surgical operation. 78-80
The authors suggest that the increased synthesis of the components of the extracellular matrix and their deposition in the subdural fluid may lead to the increase in its oncotic pressure. 77 This
notion also seems to be in line with data suggesting that exudation plays an important role in CSDH. Fujisawa et al 81 and
Tokmak et al 82 have observed a significant uptake of 99m Tc-
labeled human serum albumin into the subdural fluid, thus demonstrating that exudation takes place. EPIDEMIOLOGY The age distribution of patients with CSDH varies somewhat between published series, depending on the population from which it is derived. In a series of 2300 patients from Tivandrum, India, by Sambasivan 83 (patients treated between 1966 and 1996), the most frequent decade of presentation was 41 to 50 years. Similar to most other published series, 84-87
our recently published cohort 88 was substantially older (Figure 1). CSDH has a strong male preponderance, with a male-to-female ratio approximately 3:1. 84-87 To the best of our knowledge, a satisfactory explanation of this striking gender difference has not been published, nor has its biological basis been thoroughly investigated. PRESENTATION Most commonly, the presentation is subacute or chronic with gait disturbance, mental deterioration, headache, and limb weakness. In 10% to 20% of cases, patients present acutely with depressed level of consciousness. The relative frequency of presenting symptoms varies in different series, depending on the way the symptoms are categorized, the historical and cultural context, and the accuracy with which these were documented (Table 1). History of trauma can usually be elicited in 50% to 70% cases. 26,86-89
Numerous articles have listed predisposing factors identified in the studied populations. These are listed in Table 2. MANAGEMENT Surgical drainage is well recognized as an effective treatment of CSDH. Drainage can be achieved via craniotomy, burr hole craniostomy (BHC; 5-30 mm in diameter according to Weigel et al 2 ) or twist drill craniostomy (TDC; , 5 mm in diameter). General or local anesthesia can be used, and the procedure can be performed in the operating theater or at bedside. Numerous variations of each technique have been developed and are practiced (see also recent reviews by Weigel et al 2 and Lega et al. 90 Burr Hole Craniostomy Probably the most widely practiced treatment is evacuation via burr holes. 83,84,86,87,89,91-93 Both the systematic review by Weigel et al 2 and the decision analysis model based on the previously published data by Lega et al 90 have identified BHC as the most efficient choice to treat an ‘‘uncomplicated’’ CSDH because it balances a low recurrence rate against morbidity and mortality better than craniotomy and TDC. Over the last 2 decades, evidence has been emerging that the usage of drains with BHC is associated with lower recurrence rates. 84,87,89,94-98 In the review by Weigel et al, 2 the
use of drains was endorsed with Type B recommendation. The results of a Monte Carlo simulation in the 2009 article by Lega et al 90
an in-dwelling drain. Many surgeons remain unconvinced about the role of drains in burr hole evacuation. Results of a survey commissioned by the Society of British Neurological Surgeons in 2006 showed that most neurosurgeons in the United Kingdom and the Republic of Ireland do not use drains most of the time. 93 The perceived risk, surgeons’ experience of a patient with complications, and insufficient or a perception of insufficient evidence might play a part in their decision. q 2010 The Congress of Neurological Surgeons 115 Clinical Neurosurgery
Volume 57, 2010 Chronic Subdural Haematoma-Review Recently, we published results of a randomized con- trolled trial of the use of drains versus no drains after BHC for primary (nonrecurrent) CSDH in adults. 88 The primary end point was recurrence (reoperation) rate. The secondary Yüklə 236 Kb. Dostları ilə paylaş:
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