REVIEW URRENT C OPINION
Haemorrhage and hemicraniectomy: refining surgery for stroke Julian Bo¨sel a, Klaus Zweckberger b, and Werner Hacke a
Purpose of review Intracerebral haemorrhage is a devastating cerebrovascular disease with no established treatment. Its course is often complicated by secondary haematoma expansion and perihemorrhagic oedema. Decompressive hemicraniectomy is effective in the treatment of space-occupying hemispheric ischaemic stroke. The purpose of this review is to assess the role of decompressive hemicraniectomy in intracerebral haemorrhage. Recent findings After few small previous studies had suggested advantages by the combination of decompressive hemicraniectomy with haematoma removal, decompression on its own has been investigated within the last 5 years. Two case series and one case–control study in altogether 40 patients with severe spontaneous intracerebral haemorrhage have shown mortality rates ranging from 13 to 25% and favourable outcome from 40 to 65%. Summary Decompressive hemicraniectomy appears to be a feasible and relatively well tolerated individual treatment option for selected patients with spontaneous intracerebral haemorrhage. Data are insufficient to judge potential benefits in outcome. A randomized trial is justified and mandatory. Keywords decompressive hemicraniectomy, haematoma evacuation, haemorrhagic stroke, hemispheric stroke, intracerebral haemorrhage
INTRODUCTION Decompressive hemicraniectomy (DHC) is a neurosurgical procedure that relieves raised intracranial pressure (ICP) resulting from progressive ischaemic, haemorrhagic or traumatic brain diseases [1–4]. Secondary brain damage caused by these diseases, in particular oedema, leads to compression and midline shift within the rigid skull and compromises so far healthy brain tissue. Removal of the bone flap above the affected hemisphere and duroplasty by DHC allows the affected brain tissue to swell outwards and hence reduces ICP. So far, clinical benefits in mortality and morbidity have only been demonstrated by studies of sufficient quality for large ischaemic hemispheric stroke [’malignant’ middle cerebral artery (MCA) infarction, MMI] [1,5,6 ]. Spontaneous intracerebral haemorrhage (ICH) constitutes 15–20% of all strokes and its affected patients are burdened with a mortality rate of up to 40% and a high rate of moderate to severe disability if they survive [7–9]. Optimal conservative management of ICH, including general intensive care measures, blood pressure regulation, coagulation
and temperature management, is still unclear. Surgical treatment of ICH, that is evacuation of hematomas, is of equally unclear benefit, as two large randomized trials, STICH and STICH II have yielded neutral results [10 ,11]. It has been consistently shown that space-occupying effects in ICH, such as secondary haematoma expansion, intraventricular haemorrhage (IVH) and perihemorrhagic oedema, all contributing to the resulting lesion volume, are predictors of mortality and poor outcome [12–15]. Despite these insights, relief of spaceoccupying effects by DHC has hardly been employed or studied in patients with ICH. This review summarizes evidence gathered on DHC in &
&&
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a
Department of Neurology and bDepartment of Neurosurgery, University of Heidelberg, Heidelberg, Germany Correspondence to PD Dr. med. Julian Bo¨sel, MD, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. Tel: +49 6221 56 39145; fax: +49 6221 56 5461; e-mail: [email protected] Curr Opin Neurol 2015, 28:16–22 DOI:10.1097/WCO.0000000000000167 Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Haemorrhage and hemicraniectomy Bo ¨ sel et al.
ICH focusing on the last 5 years and discussing pathophysiological considerations between ischaemic and haemorrhagic oedema as well as potential future directions of this form of stroke treatment. Infratentorial ICH or supratentorial ICH as part of subarachnoid haemorrhage (SAH) or related to structural vascular lesions or trauma are not addressed.
compartment. As these mechanisms are not only limited to neurons but also involve neuroglia and endothelial cells, they promote disruption of the blood–brain barrier and eventually cause vasogenic oedema, also driven by inflammatory processes developing from hours to days after ischaemic stroke [16]. In the rigid skull, enlarging strokerelated oedema can hardly be compensated by reductions of the blood and cerebrospinal fluid (CSF) compartments, hence compression of as yet unaffected brain tissue or vessels and eventually rise in ICP and herniation might follow. In most patients with hemispheric stroke, secondary brain oedema develops in a fairly linear and almost predictable fashion, with a radiologically evident spaceoccupying effect beginning on day 2, peaking at days 4 or 5 [17]. In some patients, however, relevant brain oedema does not occur or occurs with delayed dynamics, for unknown reasons. Past attempts to treat oedema from MMI conservatively by nonspecific agents such as steroids, mannitol, hypertonic saline or other measures of intensive care could not be linked to benefits in outcome [18]. More recently identified treatment targets, such as specific ion and water channels and their inhibitors, as well as therapeutic hypothermia, are currently being investigated as potential options in the treatment of ischaemic brain oedema [19]. To date, the only proven effective form of treating oedema in MMI is DHC within 48 h from stroke onset [1,6 ,20].
SECONDARY BRAIN INJURY AFTER LARGE ISCHAEMIC STROKE
SECONDARY BRAIN INJURY AFTER LARGE HAEMORRHAGIC STROKE
Large hemispheric infarction in the territory of the internal carotid artery (ICA) or the MCA (and possibly adjacent territories) leads to same pathophysiological changes in the infarcted brain tissue and its vicinity as in any acute ischaemic stroke (AIS). However, due to the size of the infarction, the consequences of these mechanisms have a much greater and often fatal magnitude. In the first minutes to hours after stroke, massive release of excitatory neurotransmitters such as glutamate cause excitotoxicity, while at the same time the energy breakdown of the cells, due to cessation of oxygen and glucose supply, causes failure of the active membrane pumps and channels to stabilize the ionic membrane potential. The energy dysbalance is further enhanced by peri-infarct depolarizations that ensue over the first hours after stroke. Together, this leads to uncontrolled influx of cations into the cells dragging water after them causing, together with other factors, cytotoxic oedema. Once the capacity of cell swelling is overwhelmed, water will enter the interstitial
Although secondary brain damage after ICH might share some molecular mechanisms with that after MMI, certain distinct features should be acknowledged [21 ]. The primary impact of ICH is mechanical, with disruption of the cerebral cellular architecture within seconds. Very early, depending in its dimension on the initial size of the ICH, compression can compromise adjacent brain tissue and vessels and lead to secondary mechanical and ischaemic damage in the surroundings. In about 30% of patients, secondary haematoma expansion occurs within the first 24 h, either due to ongoing or recurring bleeding for mostly unknown reasons. Haematoma expansion with eventually enlarged final haematoma volume and/or invasion of the ventricles (IVH) is a consistent factor worsening the prognosis [15,22]. Reported attempts to prevent or ameliorate haematoma expansion have either failed or been limited to single, small studies [23], with the exception of two treatment approaches. One is the haemostatic stabilization employing substances such as recombinant factor VII, tranexamic
KEY POINTS Conservatively treated patients with space-occupying spontaneous intracerebral haemorrhage often have a high mortality and a poor functional outcome. Open surgical haematoma evacuation has not yielded convincing benefits in functional outcome, so far. Decompressive hemicraniectomy, beneficial in malignant MCA infarction, has been applied to patients with spontaneous ICH with or without haematoma evacuation. Few small case series and case–control studies of limited quality have reported benefits or trends of benefits for decompressive hemicraniectomy in spontaneous intracerebral haemorrhage. A prospective randomized trial is justified and mandatory if decompression of intracerebral haemorrhage is to be regarded more than an individual treatment option for selected patients.
&&
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&
www.co-neurology.com
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17
Cerebrovascular disease
acid or platelet infusion. The other is the early and aggressive blood pressure lowering. Although preclinical and small clinical studies have reported reduced haematoma expansion by such approaches, this could not be linked to improved outcomes [21 ,24]. Perihemorrhagic oedema evolves at a slower pace, contributes to total lesion volume and mass effect, and peaks during the second week from ICH onset in most cases [22]. Factors that promote perihemorrhagic oedema come from the clot itself, its degradation products or are a direct response of the coagulation cascade to the bleeding. They include thrombin, haemoglobin, iron and are associated with inflammation and free radicals [25]. Preclinical and first clinical studies have been started on these treatment targets, such as chelating iron by deferoxamine, but these studies are either ongoing or have not shown functional benefits. A particular challenge in targeting these factors is that most of them may on the one side be detrimental but may on the other side support regeneration. An apparent effective way to prevent or reduce perihemorrhagic oedema was achieved by therapeutic mild hypothermia applied over 10 days, however only reported in two small studies of the same group [26,27]. Because of the role of the clot itself in both early compressive damage to the surrounding tissue and in promoting secondary injury such as perihemorrhagic oedema, most surgical attempts have been directed at clot removal. As open craniotomy and haematoma evacuation have not been found to improve outcome in large randomized trials [10 ,11], current approaches involve minimally invasive (endoscopic) techniques [28] and the combination thereof with intrahaematomally applied recombinant tissue type plasminogen activator (rtPA) [29]. Data on these approaches from larger patient numbers are pending. Comparing secondary oedema from haemorrhage to that from ischaemia, the first appears to evolve later and in a less linear fashion than the latter. But haematoma expansion due to ongoing or rebleeding may create a significant space-occupying effect within the first 24 h. This would support to initiate relieving measures early after ICH. &
&
THE TECHNIQUE OF DECOMPRESSIVE HEMICRANIECTOMY WITH AND WITHOUT HAEMATOMA EVACUATION The aim of DHC is to gain space to allow the affected brain tissue to swell. Following a large skin incision, preparation of a skin-galea flap and mobilization of the temporal muscle, several boreholes are drilled parallel to the sagittal sinus, occipital and fronto-temporal. Conceding that there are no 18
www.co-neurology.com
recommendations with respect to the size of the craniectomy in ICH patients, referring to studies of ischaemic stroke, large craniectomies with a minimum of 12 cm in diameter might be advisable. In order to decompress the middle cranial fossa to prevent transtentorial herniation, temporal osteoclastic enlargement of the craniecotomy is mandatory. To achieve sufficient decompression, the dura should be opened followed by any form of duraplasty avoiding CSF leakages or infections, such as autologous or artificial materials as well as hemostyptic tissues. According to the literature, so far, no specific form of duraplasty has shown ascendency over the others. In patients with space-occupying ICH, the evacuation of the haematoma is often feasible, especially if it is located at or close to the surface of the cortex. Most surgeons might advocate microsurgical corticotomy and clot evacuation by careful aspiration or the use of forceps followed by rigorous haemostasis. Figure 1 demonstrates an example of an escalative approach to decompressive surgical treatment of ICH.
STUDIES ON DECOMPRESSIVE HEMICRANIECTOMY IN INTRACEREBRAL HAEMORRHAGE Recent comparative experimental studies in rats and mice showed that DHC after experimental ICH reduces mortality, although findings were controversial with regard to neurological outcome. Although Omary et al. [30] found no effect on haematoma volume and neurological disability in mice, the study by Marinkovic et al. [31] in rats injected with autologous blood and craniectomized after 1 h (n ¼ 10), 6 h (n ¼ 10), 24 h (n ¼ 11), compared with no craniectomy (n ¼ 20) and craniectomy without ICH (n ¼ 10), revealed more benefits. DHC resulted in significant, time-dependent (the earlier the better) reduction of mortality, poor neurological and poor behavioural outcome. In humans, most studies on DHC have involved haematoma evacuation. A recent systematic review summarized seven studies (191 patients) on DHC with hematoma evacuation (and two studies without). None of those studies was a randomized trial, and the study design was case series or case–control studies. Common findings were a patient age between 40 and 60 years, a Glasgow Coma Scale (GCS) less than 8 before surgery, a mixture of ganglionic and lobar haematomas, an ICH volume more than 60 ml, a considerable percentage of IVH and surgery within 24 h from onset. Complications after surgery were, as far as reported, hydrocephalus Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Haemorrhage and hemicraniectomy Bo ¨ sel et al.
(a)
(b)
(c)
(d)
FIGURE 1. Escalative decompressive surgical treatment of intracerebral haemorrhage. Skull computed tomography scans. (a) Right-sided ganglionic intracerebral haematoma and marked midline-shift. (b) After minimally invasive endoscopic evacuation of haematoma and placement of intraparenchymatous intracranial pressure probe, note oedema and persistent mid-line shift. (c) After decompressive hemicraniectomy. (d) Follow-up imaging after 3 months prior to reinsertion of bone-flap. Source: PD Dr med. Klaus Zweckberger, MD, private collection.
(20%), additional haemorrhage (3%) and infections (3%). Despite the preoperative characteristics mentioned that would predict a bleak clinical course, average mortality in the reviewed studies was 28% and favourable outcome 41%. The authors of the review concluded for DHC with haematoma evacuation that it appears well tolerated and effective for the treatment of large hemispheric ICH in selected patients. They emphasized the need of randomized trials and judged the effect of DHC without haematoma evacuation as inconclusive due to the small number of patients reported so far. A recent retrospective analysis involving 51 ICH patients comparing the combination of DHC and haematoma evacuation with the latter only showed significantly
reduced midline-shift and a trend to less poor outcome by the combined approach in patients with ganglionic ICH but not in those with lobar ICH [32]. Indeed, DHC only, that is without haematoma evacuation, has hardly been studied in humans. As that is the focus of the present review and the evidence has been gathered over the last 5 years, however, this form of treatment will be discussed in more detail in the following. We have identified three small, but noteworthy studies, displayed in Table 1. In a small study on five cases, Heuts et al. [33] have prospectively analysed the effects of DHC performed between the first and seventh day postICH, which was ganglionic or lobar, of a median volume of 53 ml and had led to a median preoperative
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19
20
40
DHC, decompressive hemicraniectomy; GCS, Glasgow Coma Scale; ICH, intracerebral haemorrhage; IVH, intraventricular haemorrhage; nr, not reported; preop, preoperative.
24 (40), 48 (20), >48 (40) Ganglionic (60), lobar (40) 5
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Heuts et al. [33]
Case–control
Median 43
Median 7
Median 53
40
20
75 Median 12 Ganglionic (42), lobar (58) 12
Ramnarayan et al. [34]
&
Fung et al. [35 ]
Case–control
Median 48
Median 8
Median 61
nr
25
56 13 6 (87) Ganglionic (100) 23 Case series
31–68
8 (30)
>60 (30%)
26
Mortality (%) Hours to DHC (%) Presence of IVH (%) ICH volume (ml) ICH location (%) GCS preop (%) Age (years) N Study design Author
Table 1. Recent studies on decompressive hemicraniectomy without haematoma evacuation in spontaneous supratentorial intracerebral haemorrhage
Favourable outcome (%)
Cerebrovascular disease
midline-shift of 7.6 mm. DHC was performed within 24 h in two, between 24 and 48 h in one and between 2 and 7 days in two patients. At 6 months after surgery, one patient had died, and of the four survivors, two were functionally dependent [modified Rankin Scale (mRS) 4–5] and two were functionally independent (mRS 0–3). These five patients were compared with five nonoperated similar controls and 144 nonselected ICH patients from the centre’s registry who were mostly treated conservatively. It turned out that the DHC patients had a lower mortality and mRS (20%, 4) than the matched controls (60%, 6) and the nonselected controls (47%, 5), although this was not statistically significant [33]. In a larger case series, Ramnarayan et al. [34] subjected 23 patients with ganglionic ICH to DHC only. Age was 31–68 years, GCS was below 8 in 30% and ICH volume was more than 60 ml in 30% of patients. After 3 months, 56% had a favourable outcome, 30% an unfavourable outcome and 14% had died [34]. In a small retrospective case–control study, Fung et al. [35 ] compared 12 ICH patients treated by DHC without haematoma evacuation with 15 matched patients treated conservatively. The 12 patients had a median age of 48 years, a median preoperative GCS of 8 and a median haematoma volume of 61 ml, hence constituted a very severely affected ICH population. Three patients (25%) died, while nine (75%) survived with a favourable outcome (mRS at 6 months 0–4), compared with a mortality of 53% and survival with favourable outcome of 47% in the matched control group. Despite clear trends, these results were not statistically significant, certainly owing to the small sample size. Surgical complications of DHC in the 15 patients were remote haemorrhage (one), subdural haematoma (one), subdural empyema (one) and aseptical bone resorption after cranioplasty (1), and were judged manageable [35 ]. The results of these studies, as well as of those on DHC with haematoma evacuation, have to be interpreted with great caution, as these small and often retrospective case series or case–control studies do not only suffer from selection and detection bias but also involve substantial heterogeneity with regard to ICH origin, size, location and presence of IVH, and with regard to patient characteristics and method and time of outcome assessment. &
&
FUTURE DIRECTIONS Given the poor prognosis of conservatively managed ICH, the neutral results of trials on surgical clot removal alone and the results on safety and feasibility of DHC from the above-named – admittedly low quality – studies in altogether more than 200 patients, a randomized trial appears justified. Volume 28 Number 1 February 2015
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Haemorrhage and hemicraniectomy Bo ¨ sel et al.
That trial should answer, at best, whether DHC alone or DHC combined with haematoma evacuation is superior to conservative treatment with regard to outcome. Ideally, a three-arm trial should compare guideline-based best medical treatment with DHC alone and DHC combined with haematoma evacuation. As this would result in a very high sample size, a two-arm randomized controlled trial (RCT) comparing the first two treatment options may be preferred. The trial should be limited to either lobar or ganglionic ICH or recruit enough patients to allow for later subgroup analysis with regard to that. Inclusion criteria should contain a haematoma volume of more than 30 ml (and probably less than 90 ml), some degree of midline-shift on admission computed tomography (CT) and a decline in level of consciousness (e.g. GCS
Haemorrhage and hemicraniectomy: refining surgery for stroke Julian Bo¨sel a, Klaus Zweckberger b, and Werner Hacke a
Purpose of review Intracerebral haemorrhage is a devastating cerebrovascular disease with no established treatment. Its course is often complicated by secondary haematoma expansion and perihemorrhagic oedema. Decompressive hemicraniectomy is effective in the treatment of space-occupying hemispheric ischaemic stroke. The purpose of this review is to assess the role of decompressive hemicraniectomy in intracerebral haemorrhage. Recent findings After few small previous studies had suggested advantages by the combination of decompressive hemicraniectomy with haematoma removal, decompression on its own has been investigated within the last 5 years. Two case series and one case–control study in altogether 40 patients with severe spontaneous intracerebral haemorrhage have shown mortality rates ranging from 13 to 25% and favourable outcome from 40 to 65%. Summary Decompressive hemicraniectomy appears to be a feasible and relatively well tolerated individual treatment option for selected patients with spontaneous intracerebral haemorrhage. Data are insufficient to judge potential benefits in outcome. A randomized trial is justified and mandatory. Keywords decompressive hemicraniectomy, haematoma evacuation, haemorrhagic stroke, hemispheric stroke, intracerebral haemorrhage
INTRODUCTION Decompressive hemicraniectomy (DHC) is a neurosurgical procedure that relieves raised intracranial pressure (ICP) resulting from progressive ischaemic, haemorrhagic or traumatic brain diseases [1–4]. Secondary brain damage caused by these diseases, in particular oedema, leads to compression and midline shift within the rigid skull and compromises so far healthy brain tissue. Removal of the bone flap above the affected hemisphere and duroplasty by DHC allows the affected brain tissue to swell outwards and hence reduces ICP. So far, clinical benefits in mortality and morbidity have only been demonstrated by studies of sufficient quality for large ischaemic hemispheric stroke [’malignant’ middle cerebral artery (MCA) infarction, MMI] [1,5,6 ]. Spontaneous intracerebral haemorrhage (ICH) constitutes 15–20% of all strokes and its affected patients are burdened with a mortality rate of up to 40% and a high rate of moderate to severe disability if they survive [7–9]. Optimal conservative management of ICH, including general intensive care measures, blood pressure regulation, coagulation
and temperature management, is still unclear. Surgical treatment of ICH, that is evacuation of hematomas, is of equally unclear benefit, as two large randomized trials, STICH and STICH II have yielded neutral results [10 ,11]. It has been consistently shown that space-occupying effects in ICH, such as secondary haematoma expansion, intraventricular haemorrhage (IVH) and perihemorrhagic oedema, all contributing to the resulting lesion volume, are predictors of mortality and poor outcome [12–15]. Despite these insights, relief of spaceoccupying effects by DHC has hardly been employed or studied in patients with ICH. This review summarizes evidence gathered on DHC in &
&&
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a
Department of Neurology and bDepartment of Neurosurgery, University of Heidelberg, Heidelberg, Germany Correspondence to PD Dr. med. Julian Bo¨sel, MD, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. Tel: +49 6221 56 39145; fax: +49 6221 56 5461; e-mail: [email protected] Curr Opin Neurol 2015, 28:16–22 DOI:10.1097/WCO.0000000000000167 Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Haemorrhage and hemicraniectomy Bo ¨ sel et al.
ICH focusing on the last 5 years and discussing pathophysiological considerations between ischaemic and haemorrhagic oedema as well as potential future directions of this form of stroke treatment. Infratentorial ICH or supratentorial ICH as part of subarachnoid haemorrhage (SAH) or related to structural vascular lesions or trauma are not addressed.
compartment. As these mechanisms are not only limited to neurons but also involve neuroglia and endothelial cells, they promote disruption of the blood–brain barrier and eventually cause vasogenic oedema, also driven by inflammatory processes developing from hours to days after ischaemic stroke [16]. In the rigid skull, enlarging strokerelated oedema can hardly be compensated by reductions of the blood and cerebrospinal fluid (CSF) compartments, hence compression of as yet unaffected brain tissue or vessels and eventually rise in ICP and herniation might follow. In most patients with hemispheric stroke, secondary brain oedema develops in a fairly linear and almost predictable fashion, with a radiologically evident spaceoccupying effect beginning on day 2, peaking at days 4 or 5 [17]. In some patients, however, relevant brain oedema does not occur or occurs with delayed dynamics, for unknown reasons. Past attempts to treat oedema from MMI conservatively by nonspecific agents such as steroids, mannitol, hypertonic saline or other measures of intensive care could not be linked to benefits in outcome [18]. More recently identified treatment targets, such as specific ion and water channels and their inhibitors, as well as therapeutic hypothermia, are currently being investigated as potential options in the treatment of ischaemic brain oedema [19]. To date, the only proven effective form of treating oedema in MMI is DHC within 48 h from stroke onset [1,6 ,20].
SECONDARY BRAIN INJURY AFTER LARGE ISCHAEMIC STROKE
SECONDARY BRAIN INJURY AFTER LARGE HAEMORRHAGIC STROKE
Large hemispheric infarction in the territory of the internal carotid artery (ICA) or the MCA (and possibly adjacent territories) leads to same pathophysiological changes in the infarcted brain tissue and its vicinity as in any acute ischaemic stroke (AIS). However, due to the size of the infarction, the consequences of these mechanisms have a much greater and often fatal magnitude. In the first minutes to hours after stroke, massive release of excitatory neurotransmitters such as glutamate cause excitotoxicity, while at the same time the energy breakdown of the cells, due to cessation of oxygen and glucose supply, causes failure of the active membrane pumps and channels to stabilize the ionic membrane potential. The energy dysbalance is further enhanced by peri-infarct depolarizations that ensue over the first hours after stroke. Together, this leads to uncontrolled influx of cations into the cells dragging water after them causing, together with other factors, cytotoxic oedema. Once the capacity of cell swelling is overwhelmed, water will enter the interstitial
Although secondary brain damage after ICH might share some molecular mechanisms with that after MMI, certain distinct features should be acknowledged [21 ]. The primary impact of ICH is mechanical, with disruption of the cerebral cellular architecture within seconds. Very early, depending in its dimension on the initial size of the ICH, compression can compromise adjacent brain tissue and vessels and lead to secondary mechanical and ischaemic damage in the surroundings. In about 30% of patients, secondary haematoma expansion occurs within the first 24 h, either due to ongoing or recurring bleeding for mostly unknown reasons. Haematoma expansion with eventually enlarged final haematoma volume and/or invasion of the ventricles (IVH) is a consistent factor worsening the prognosis [15,22]. Reported attempts to prevent or ameliorate haematoma expansion have either failed or been limited to single, small studies [23], with the exception of two treatment approaches. One is the haemostatic stabilization employing substances such as recombinant factor VII, tranexamic
KEY POINTS Conservatively treated patients with space-occupying spontaneous intracerebral haemorrhage often have a high mortality and a poor functional outcome. Open surgical haematoma evacuation has not yielded convincing benefits in functional outcome, so far. Decompressive hemicraniectomy, beneficial in malignant MCA infarction, has been applied to patients with spontaneous ICH with or without haematoma evacuation. Few small case series and case–control studies of limited quality have reported benefits or trends of benefits for decompressive hemicraniectomy in spontaneous intracerebral haemorrhage. A prospective randomized trial is justified and mandatory if decompression of intracerebral haemorrhage is to be regarded more than an individual treatment option for selected patients.
&&
1350-7540 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
&
www.co-neurology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
17
Cerebrovascular disease
acid or platelet infusion. The other is the early and aggressive blood pressure lowering. Although preclinical and small clinical studies have reported reduced haematoma expansion by such approaches, this could not be linked to improved outcomes [21 ,24]. Perihemorrhagic oedema evolves at a slower pace, contributes to total lesion volume and mass effect, and peaks during the second week from ICH onset in most cases [22]. Factors that promote perihemorrhagic oedema come from the clot itself, its degradation products or are a direct response of the coagulation cascade to the bleeding. They include thrombin, haemoglobin, iron and are associated with inflammation and free radicals [25]. Preclinical and first clinical studies have been started on these treatment targets, such as chelating iron by deferoxamine, but these studies are either ongoing or have not shown functional benefits. A particular challenge in targeting these factors is that most of them may on the one side be detrimental but may on the other side support regeneration. An apparent effective way to prevent or reduce perihemorrhagic oedema was achieved by therapeutic mild hypothermia applied over 10 days, however only reported in two small studies of the same group [26,27]. Because of the role of the clot itself in both early compressive damage to the surrounding tissue and in promoting secondary injury such as perihemorrhagic oedema, most surgical attempts have been directed at clot removal. As open craniotomy and haematoma evacuation have not been found to improve outcome in large randomized trials [10 ,11], current approaches involve minimally invasive (endoscopic) techniques [28] and the combination thereof with intrahaematomally applied recombinant tissue type plasminogen activator (rtPA) [29]. Data on these approaches from larger patient numbers are pending. Comparing secondary oedema from haemorrhage to that from ischaemia, the first appears to evolve later and in a less linear fashion than the latter. But haematoma expansion due to ongoing or rebleeding may create a significant space-occupying effect within the first 24 h. This would support to initiate relieving measures early after ICH. &
&
THE TECHNIQUE OF DECOMPRESSIVE HEMICRANIECTOMY WITH AND WITHOUT HAEMATOMA EVACUATION The aim of DHC is to gain space to allow the affected brain tissue to swell. Following a large skin incision, preparation of a skin-galea flap and mobilization of the temporal muscle, several boreholes are drilled parallel to the sagittal sinus, occipital and fronto-temporal. Conceding that there are no 18
www.co-neurology.com
recommendations with respect to the size of the craniectomy in ICH patients, referring to studies of ischaemic stroke, large craniectomies with a minimum of 12 cm in diameter might be advisable. In order to decompress the middle cranial fossa to prevent transtentorial herniation, temporal osteoclastic enlargement of the craniecotomy is mandatory. To achieve sufficient decompression, the dura should be opened followed by any form of duraplasty avoiding CSF leakages or infections, such as autologous or artificial materials as well as hemostyptic tissues. According to the literature, so far, no specific form of duraplasty has shown ascendency over the others. In patients with space-occupying ICH, the evacuation of the haematoma is often feasible, especially if it is located at or close to the surface of the cortex. Most surgeons might advocate microsurgical corticotomy and clot evacuation by careful aspiration or the use of forceps followed by rigorous haemostasis. Figure 1 demonstrates an example of an escalative approach to decompressive surgical treatment of ICH.
STUDIES ON DECOMPRESSIVE HEMICRANIECTOMY IN INTRACEREBRAL HAEMORRHAGE Recent comparative experimental studies in rats and mice showed that DHC after experimental ICH reduces mortality, although findings were controversial with regard to neurological outcome. Although Omary et al. [30] found no effect on haematoma volume and neurological disability in mice, the study by Marinkovic et al. [31] in rats injected with autologous blood and craniectomized after 1 h (n ¼ 10), 6 h (n ¼ 10), 24 h (n ¼ 11), compared with no craniectomy (n ¼ 20) and craniectomy without ICH (n ¼ 10), revealed more benefits. DHC resulted in significant, time-dependent (the earlier the better) reduction of mortality, poor neurological and poor behavioural outcome. In humans, most studies on DHC have involved haematoma evacuation. A recent systematic review summarized seven studies (191 patients) on DHC with hematoma evacuation (and two studies without). None of those studies was a randomized trial, and the study design was case series or case–control studies. Common findings were a patient age between 40 and 60 years, a Glasgow Coma Scale (GCS) less than 8 before surgery, a mixture of ganglionic and lobar haematomas, an ICH volume more than 60 ml, a considerable percentage of IVH and surgery within 24 h from onset. Complications after surgery were, as far as reported, hydrocephalus Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Haemorrhage and hemicraniectomy Bo ¨ sel et al.
(a)
(b)
(c)
(d)
FIGURE 1. Escalative decompressive surgical treatment of intracerebral haemorrhage. Skull computed tomography scans. (a) Right-sided ganglionic intracerebral haematoma and marked midline-shift. (b) After minimally invasive endoscopic evacuation of haematoma and placement of intraparenchymatous intracranial pressure probe, note oedema and persistent mid-line shift. (c) After decompressive hemicraniectomy. (d) Follow-up imaging after 3 months prior to reinsertion of bone-flap. Source: PD Dr med. Klaus Zweckberger, MD, private collection.
(20%), additional haemorrhage (3%) and infections (3%). Despite the preoperative characteristics mentioned that would predict a bleak clinical course, average mortality in the reviewed studies was 28% and favourable outcome 41%. The authors of the review concluded for DHC with haematoma evacuation that it appears well tolerated and effective for the treatment of large hemispheric ICH in selected patients. They emphasized the need of randomized trials and judged the effect of DHC without haematoma evacuation as inconclusive due to the small number of patients reported so far. A recent retrospective analysis involving 51 ICH patients comparing the combination of DHC and haematoma evacuation with the latter only showed significantly
reduced midline-shift and a trend to less poor outcome by the combined approach in patients with ganglionic ICH but not in those with lobar ICH [32]. Indeed, DHC only, that is without haematoma evacuation, has hardly been studied in humans. As that is the focus of the present review and the evidence has been gathered over the last 5 years, however, this form of treatment will be discussed in more detail in the following. We have identified three small, but noteworthy studies, displayed in Table 1. In a small study on five cases, Heuts et al. [33] have prospectively analysed the effects of DHC performed between the first and seventh day postICH, which was ganglionic or lobar, of a median volume of 53 ml and had led to a median preoperative
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19
20
40
DHC, decompressive hemicraniectomy; GCS, Glasgow Coma Scale; ICH, intracerebral haemorrhage; IVH, intraventricular haemorrhage; nr, not reported; preop, preoperative.
24 (40), 48 (20), >48 (40) Ganglionic (60), lobar (40) 5
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Heuts et al. [33]
Case–control
Median 43
Median 7
Median 53
40
20
75 Median 12 Ganglionic (42), lobar (58) 12
Ramnarayan et al. [34]
&
Fung et al. [35 ]
Case–control
Median 48
Median 8
Median 61
nr
25
56 13 6 (87) Ganglionic (100) 23 Case series
31–68
8 (30)
>60 (30%)
26
Mortality (%) Hours to DHC (%) Presence of IVH (%) ICH volume (ml) ICH location (%) GCS preop (%) Age (years) N Study design Author
Table 1. Recent studies on decompressive hemicraniectomy without haematoma evacuation in spontaneous supratentorial intracerebral haemorrhage
Favourable outcome (%)
Cerebrovascular disease
midline-shift of 7.6 mm. DHC was performed within 24 h in two, between 24 and 48 h in one and between 2 and 7 days in two patients. At 6 months after surgery, one patient had died, and of the four survivors, two were functionally dependent [modified Rankin Scale (mRS) 4–5] and two were functionally independent (mRS 0–3). These five patients were compared with five nonoperated similar controls and 144 nonselected ICH patients from the centre’s registry who were mostly treated conservatively. It turned out that the DHC patients had a lower mortality and mRS (20%, 4) than the matched controls (60%, 6) and the nonselected controls (47%, 5), although this was not statistically significant [33]. In a larger case series, Ramnarayan et al. [34] subjected 23 patients with ganglionic ICH to DHC only. Age was 31–68 years, GCS was below 8 in 30% and ICH volume was more than 60 ml in 30% of patients. After 3 months, 56% had a favourable outcome, 30% an unfavourable outcome and 14% had died [34]. In a small retrospective case–control study, Fung et al. [35 ] compared 12 ICH patients treated by DHC without haematoma evacuation with 15 matched patients treated conservatively. The 12 patients had a median age of 48 years, a median preoperative GCS of 8 and a median haematoma volume of 61 ml, hence constituted a very severely affected ICH population. Three patients (25%) died, while nine (75%) survived with a favourable outcome (mRS at 6 months 0–4), compared with a mortality of 53% and survival with favourable outcome of 47% in the matched control group. Despite clear trends, these results were not statistically significant, certainly owing to the small sample size. Surgical complications of DHC in the 15 patients were remote haemorrhage (one), subdural haematoma (one), subdural empyema (one) and aseptical bone resorption after cranioplasty (1), and were judged manageable [35 ]. The results of these studies, as well as of those on DHC with haematoma evacuation, have to be interpreted with great caution, as these small and often retrospective case series or case–control studies do not only suffer from selection and detection bias but also involve substantial heterogeneity with regard to ICH origin, size, location and presence of IVH, and with regard to patient characteristics and method and time of outcome assessment. &
&
FUTURE DIRECTIONS Given the poor prognosis of conservatively managed ICH, the neutral results of trials on surgical clot removal alone and the results on safety and feasibility of DHC from the above-named – admittedly low quality – studies in altogether more than 200 patients, a randomized trial appears justified. Volume 28 Number 1 February 2015
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Haemorrhage and hemicraniectomy Bo ¨ sel et al.
That trial should answer, at best, whether DHC alone or DHC combined with haematoma evacuation is superior to conservative treatment with regard to outcome. Ideally, a three-arm trial should compare guideline-based best medical treatment with DHC alone and DHC combined with haematoma evacuation. As this would result in a very high sample size, a two-arm randomized controlled trial (RCT) comparing the first two treatment options may be preferred. The trial should be limited to either lobar or ganglionic ICH or recruit enough patients to allow for later subgroup analysis with regard to that. Inclusion criteria should contain a haematoma volume of more than 30 ml (and probably less than 90 ml), some degree of midline-shift on admission computed tomography (CT) and a decline in level of consciousness (e.g. GCS
