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Malignant middle cerebral artery (MCA) infarction: pathophysiology, diagnosis and management
  1. Sean D Treadwell1,
  2. Bhomraj Thanvi2
  1. 1University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK
  2. 2South Warwickshire Hospital, Warwick, UK
  1. Correspondence to Dr Sean D Treadwell, Consultant Stroke Physician, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester LE5 4PW, UK; seantreadwell{at}hotmail.com

Abstract

‘Malignant MCA infarction’ is the term used to describe rapid neurological deterioration due to the effects of space occupying cerebral oedema following middle cerebral artery (MCA) territory stroke. Early neurological decline and symptoms such as headache and vomiting should alert the clinician to this syndrome, supported by radiological evidence of cerebral oedema and mass effect in the context of large hemispheric infarction. The prognosis is generally poor, and death usually occurs as a result of transtentorial herniation and brainstem compression. Treatment options include general measures and pharmacological agents to limit the extent of oedema, and surgical decompression to relieve the pressure effects. Until recently there has been little evidence to guide appropriate treatment, though in the last few years randomised data have been published addressing the role of surgical decompression. A pooled analysis of three European randomised controlled trials suggests that hemicraniectomy performed within 48 h significantly reduces mortality, and improves functional outcome in selected patients, and this has been reflected in recent national guidelines.

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Introduction

In the UK stroke remains an important cause of death and disability, and occlusion of the middle cerebral artery (MCA) or one of its branches is one of the more common causes of ischaemic stroke. Space occupying oedema is the leading cause of mortality in the first week following stroke,1 and clinical features usually manifest between the second and fourth day. However, neurological deterioration may occur more rapidly within 24 h of symptom onset, and when associated with involvement of the whole MCA territory has been termed ‘malignant MCA infarction’. The annual incidence is between 10 and 20 per 100 000 people, and females are more commonly affected.2–4 The prognosis is generally poor, and mortality has been reported in up to 80%.5 Here we shall review the underlying pathophysiology of the condition, the clinical and radiological manifestations, and consider the evidence for the various pharmacological and surgical treatment options available.

Pathophysiology of ischaemic cerebral oedema

Progressive brain oedema following ischaemic stroke exerts a mechanical force on surrounding tissue structures. This occurs within the fixed volume of the intracranial cavity, and is therefore at the expense of other compartments, namely the vasculature and cerebrospinal fluid (CSF) space. Once accommodative mechanisms are exhausted, intracranial pressure (ICP) starts to rise. Consequently, cerebral blood flow is compromised, with failure of autoregulation and worsening ischaemia. Rising ICP may then result in tissue shifts, with transtentorial and uncal herniation leading to progressive brainstem dysfunction. At a molecular level, ischaemic cerebral oedema typically consists of both cytotoxic (intracellular) and vasogenic (extracellular) oedema, though there is much overlap, and this distinction is likely to be an oversimplification.

Cytotoxic oedema

Cytotoxic oedema occurs within minutes of ischaemic injury and results in movement of water from the extracellular to the intracellular space without disruption of the blood–brain barrier (BBB).6 7 This is not associated with an overall increase in brain volume and therefore does not contribute to significant swelling. Tissue ischaemia leads to reduced availability of oxygen and glucose which compromises energy dependent primary active transport systems.8 Failure of the Na+/K+ pump leads to an influx of Na+ and progressive loss of the ionic gradient, resulting in membrane depolarisation. Accumulation of intracellular Na+ generates an osmotic force resulting in secondary inflow of water from the extracellular space leading to cell swelling. Membrane failure also leads to the opening of channels which allow calcium influx,9 contributing to cell injury. This process eventually leads to membrane rupture and cell death.10

Vasogenic oedema

Vasogenic oedema is characterised by the movement of proteins and fluid from the intravascular to the interstitial space due to disruption of the BBB. Depletion of extracellular Na+ secondary to early cytotoxic oedema provides the initial driving force for the development of vasogenic oedema, by the formation of a Na+ and water gradient across the intact BBB.11 The later stages of vasogenic oedema are characterised by a breakdown in the BBB, with leakage of intravascular proteins and ions into the extracellular space. In this instance, hydrostatic pressure gradients determined by systemic blood pressure and ICP assume importance alongside osmotic pressure gradients in the formation of oedema. The exact mechanism whereby ischaemic injury disrupts the BBB is not fully understood, though active pinocytosis by endothelial cells appears to occur early, with disruption of the tight junctions a later feature.12–14 The role of ischaemia induced mediators including matrix metalloproteinases,15 16 nitric oxide synthase,17 vascular endothelial growth factors,18 and thrombin19 have all been suggested.

Clinical features

Clinically, patients typically present with signs of severe hemispheric syndrome including hemiparesis, gaze deviation, and higher cortical signs such as language and visuo-spatial deficits. Younger patients are generally more susceptible due to the absence of cerebral atrophy, and lack of potential compensatory space within the intracranial cavity. Following ischaemic stroke, the clinical features of cerebral oedema usually manifest between the second and fourth day, though in cases of malignant MCA infarction these occur earlier within 24 h of onset.20 Symptoms and signs which suggest the development of space occupying oedema include headache, vomiting, papilloedema, deteriorating neurological function, and reduced conscious level. It should be noted, however, that there are a number of other important causes of early deterioration following acute ischaemic stroke21 which are summarised in table 1. Systemic complications tend to occur later than neurological factors, though either may occur early on.

Table 1

Causes of early deterioration following ischaemic stroke

The mortality rate of acute ischaemic MCA territory stroke is between 5–45%22 though it has been reported to be up to 80% when associated with space occupying oedema, despite maximal conservative treatment.5 Transtentorial herniation is the most common cause of death following malignant MCA infarction. Factors which determine the variable extent of ischaemic cerebral oedema in individual cases is not well established. A number of clinical predictors of fatal cerebral oedema and poor outcome have been identified,23–25 and these have been outlined alongside radiological predictors in table 2.

Table 2

Clinical and radiological predictors of cerebral oedema and poor outcome following ischaemic stroke

Neuroimaging

Computed tomography (CT) typically demonstrates early ischaemic changes in the MCA distribution within the first few hours following stroke. These consist of subtle attenuation change initially involving the grey matter which appears darker, and isointense with respect to surrounding white matter. This results in the loss of normal grey–white matter differentiation at the cortex, loss of distinction of the lentiform nucleus, and loss of the insular ribbon. Early swelling results in effacement of the cortical sulci. As the infarct progresses, the white matter also becomes hypoattenuated resulting in a distinct area of infarction (figure 1). The ‘hyperdense MCA sign’ may be seen due to thrombus within the proximal portion of the MCA, and involvement of more distal branches within the sylvian fissure seen as the ‘MCA dot sign’ (figure 2). Increasing oedema due to extensive infarction may result in space occupying features with compression of adjacent structures, midline shift, and eventually herniation.

Figure 1

CT head scan demonstrating early subtle low attenuation change with loss of the normal grey–white matter differentiation in the left middle cerebral artery (MCA) territory (white arrows) (A). Repeat imaging 24 h later shows established left MCA infarct with extensive oedema and midline shift (B).

Figure 2

CT head scan in different patients demonstrating left ‘hyperdense middle cerebral artery (MCA) sign’ (A) and right ‘MCA dot sign’ in the sylvian fissure (B), suggesting thrombus within the proximal MCA, and more distal branches respectively (white arrows).

A number of radiological findings may predict the development of malignant MCA infarction. Early ischaemic change on CT affecting >50% of the MCA territory has been shown to reliably predict subsequent oedema formation associated with poor outcome in a number of studies.23 26 27 Involvement of additional vascular territories23 and horizontal displacement of the pineal gland28 are also associated with high mortality. Patients with malignant MCA infarction demonstrate more than two thirds involvement of the MCA territory on CT perfusion maps, with a high sensitivity (91%) and specificity (94%).29 Pronounced activity deficits on early single photon emission computed tomography (SPECT) scans have predicted malignant MCA infarction more accurately than CT changes or clinical features.30 Early diffusion weighted magnetic resonance imaging (MRI) has been shown to predict malignant MCA infarction accurately. Lesion volume >145 cm3 predicted this with 100% sensitivity and 94% specificity,31 and in a further study, apparent diffusion coefficient (ADC) >82 ml predicted this with 87% sensitivity and 91% specificity.32

Treatment

The management of patients with malignant MCA infarction should generally follow standard guidelines for acute ischaemic stroke. These have been detailed extensively elsewhere, and are outside the scope of this article. Here we shall address just those issues relating to the management of cerebral oedema complicating acute stroke.

General measures

Head elevation

Head elevation may reduce ICP by promoting venous outflow. Patients with traumatic brain injury (TBI) with elevated ICP are therefore usually nursed with moderate (30°) head elevation.33 However, this practice cannot be easily translated to patients with acute ischaemic stroke, as head elevation may also result in reduced cerebral perfusion pressure (CPP),34 further compromising already ischaemic brain tissue. Schwarz et al studied the effects of body position on ICP and CPP in patients with large MCA territory stroke.35 There was only a slight reduction in ICP associated with 30° head tilt, and this was at the expense of a more significant reduction in CPP. The authors concluded that this did not support the routine use of head elevation in this situation, though it should be noted that patients with acute ICP crises were excluded from this study.

Hyperventilation

Hypoxia and hypercarbia are potent cerebral vasodilators, and so hyperventilation lowers ICP by inducing hypocarbia, with resultant cerebral vasoconstriction. This effect has been demonstrated widely in patients with TBI,36 though data on functional outcome are lacking. Concerns in patients with ischaemic stroke arise from potential worsening of the hypoxic injury due to vasoconstriction,37 and the possibility of rebound vasodilatation after treatment discontinuation resulting in further ICP elevation. Hyperventilation is therefore generally not recommended in this instance, though may be considered as a holding measure until more definitive treatment is initiated.

Hypothermia

The deleterious effects of hyperthermia on stroke outcome are well established,38 though the role of therapeutic hypothermia is less well clear. Hypothermia is likely to exert a number of neuroprotective effects, and has been shown to reduce infarct size and improve outcome in a number of animal models.39 40 However, a number of safety concerns have arisen due to documented side effects of cardiac arrhythmia,41 infection,42 coagulopathy,43 and rebound intracranial hypertension associated with re-warming. Schwab et al44 studied the efficacy and safety of induced moderate hypothermia in 25 patients with acute MCA infarction associated with raised ICP. Hypothermia was induced 14 h (mean) from onset of ischaemia by external cooling with cooling blankets, and maintained at 33°C for 48 to 72 h. The mortality rate was just 44%, and survivors reached a favourable outcome with a mean Barthel Index of 70 at 3 months. Since then a number of observational studies in patients with space occupying MCA infarction have demonstrated similar mortality rates and favourable outcomes associated with therapeutic hypothermia,45–48 though larger randomised trials are needed.

Pharmacological agents

The rationale behind the use of osmotherapy for raised ICP is to create an osmotic gradient across the BBB, drawing water from the interstitial and intracellular space within the brain. The effects of osmotic agents in experimental models on the nervous system were noted as far back as 1919,49 and since then a number of different agents have been used. Agents which produce a more favourable osmotic gradient are those which are excluded by the intact BBB to a greater degree. Problems may arise in areas where the BBB is disrupted, resulting in reversal of the osmotic gradient and rebound cerebral oedema,50 especially on treatment withdrawal. This is clearly relevant in acute stroke where large areas of the BBB may be disrupted, and may also cause preferential effects on the normal hemisphere where BBB remains intact, thus worsening tissue shifts.51

Mannitol

Mannitol, a derivative of mannose, has remained one of the most frequently used osmotic agents for the treatment of cerebral oedema since its introduction in the 1960s. It has widespread use within neurosurgical centres for the treatment of raised ICP.52 As well as its osmotic properties, mannitol may have additional neuroprotective effects related to free radical scavenging,53 inhibition of apoptosis,54 and increase in CPP.55 Mannitol is effective at reducing ICP in patients with TBI,56 57 though effects on long term outcome are less clear. In a series of 105 patients with raised ICP due to a variety of intracranial pathology, James et al demonstrated a mean ICP reduction of 52% in patients treated with bolus mannitol.58 It is traditionally administered at a dose of 0.25–2 g/kg as an intravenous bolus injection, repeated if necessary at 4–8 h, guided by a target serum osmolality of 310–320 mOsm/l.

Despite its general widespread use in other settings, data surrounding the use of mannitol for space occupying oedema related to acute ischaemic stroke are lacking. Animal experiments investigating the effects of mannitol on infarct size and cerebral oedema have demonstrated both positive59 and negative results60 on outcome. As previously mentioned, osmotic agents may have detrimental effects in acute stroke due to disruption of the BBB, and mannitol has been identified in the CSF 8 h following intravenous administration.61 In an observational study involving 800 patients with acute stroke, there was no benefit associated with mannitol use.62 A recent Cochrane report63 which reviewed the use of mannitol for acute stroke identified three randomised trials fulfilling selection criteria which included just 226 patients. The reviewers concluded that there was currently insufficient evidence to guide the routine use of mannitol in acute stroke. Its effect on stroke outcome remains unclear, and its use in malignant MCA infarction is based upon experimental and non-randomised studies. Recent guidelines have therefore given mannitol a class IIa recommendation for the treatment of deteriorating patients with malignant brain oedema following large cerebral infarction.64

Hypertonic saline

The osmotic properties of hypertonic saline within the nervous system were first noted in experimental models back in 1919.49 Sodium chloride is excluded from the BBB to a greater degree than mannitol, suggesting that it is a more potent osmotic agent. Unlike mannitol it does not lead to intravascular volume depletion, and its use as an alternative osmotic agent has increased in recent years. However, concerns surround potential complications, most notably central pontine myelinolysis related to severe hypernatraemia, and rebound hyponatraemia following treatment withdrawal. Other potential complications include other electrolyte disturbances, congestive cardiac failure, and cardiac arrhythmias.

A number of experimental and animal models have suggested that hypertonic saline is at least as effective, or even superior to mannitol at lowering ICP,65–67 and also in the clinical setting in patients with a variety of diagnoses.68 69 However, there are limited data surrounding the use of hypertonic saline for stroke related oedema in clinical practice. Schwarz et al70 studied the effects of hypertonic saline in eight patients with raised ICP related to stroke (six hemispheric infarction, two intracerebral haemorrhage (ICH)) where mannitol treatment had proved ineffective. A 75 ml bolus of 10% saline effectively reduced ICP in all cases, and led to increased CPP, though by the end of the study four patients had died, and the remainder were left severely disabled. Although hypertonic saline has been shown to effectively reduce elevated ICP in acute stroke, there are no data evaluating long term outcome measures.

Glycerol

Glycerol is an osmotic agent which crosses the BBB more readily than either mannitol or hypertonic saline; though as it is metabolised by the brain, it appears to have a lower risk of causing rebound oedema.71 A recent Cochrane report identified 11 randomised trials comparing glycerol with control in acute stroke.72 By the end of follow-up glycerol was not associated with any significant difference in mortality or functional outcome. However, these trials included both ischaemic and haemorrhagic stroke, and did not look specifically at patients with cerebral oedema. In fact, many of the patients did not even undergo neuroimaging. There is therefore no evidence to support the routine use of glycerol in the management of malignant MCA infarction.

THAM

Tris-hydroxy-methyl-aminomethane (THAM) may reduce ICP by neutralisation of acidosis related vasodilatation.73 THAM has been shown to lower elevated ICP in both animal models74 and in patients with TBI75 (though without effect on neurological outcome); however, it has not been studied in patients with space occupying cerebral infarction.

Barbiturates

Barbiturates lower ICP by lowering cerebral metabolic activity, and may be used to treat oedema refractory to other measures. Results have been inconclusive regarding the use of barbiturates in the setting of TBI,76 77 and there are no randomised data looking at their use in stroke. In a prospective series, Schwab et al found barbiturates to be initially successful in treating cerebral oedema secondary to MCA infarction when other measures had failed, although only five out of 60 consecutive patients survived.78

Corticosteroids

Steroids act to stabilise the BBB and are effective at treating vasogenic oedema associated with intracranial tumours.79 Through this mechanism one may expect similar results in the treatment of infarct related oedema, and there has been some success noted in animal models.80 However, a recent Cochrane report81 which included seven randomised trials involving 453 patients failed to demonstrate any improvement in functional outcome or mortality in patients with acute stroke treated with corticosteroids compared to placebo.

Decompressive surgery

The rationale for decompressive surgery in patients with space occupying oedema due to massive cerebral infarction is to relieve the high ICP by creating additional space for the oedematous brain to expand, thus preserving cerebral blood flow and preventing downward herniation. It should be noted that massive cerebral infarction may lead to considerable neurological deficit in the absence of significant oedema, and these patients would clearly not benefit from decompressive surgery. The procedure involves hemicraniectomy with resection of a large bone flap ipsilateral to the side of the infarct, followed by duraplasty.

Provision of stroke services varies both at a local and national level across the UK. Comprehensive stroke centres with on-site neurosurgical availability generally have facilities to take referrals from other centres within a ‘hub and spoke’ model of care. The development of clinical networks is designed to improve the pathway of care, though referral processes will clearly be dictated by access and availability to specialist neurosurgical centres, and should be agreed at a local level.

Decompressive surgery was initially described in 1905,82 and first performed in the context of cerebral infarction in 1956.83 Since then, numerous case reports and case series have demonstrated potential benefits in patients with malignant MCA infarction,84–88 though until recently there have been no randomised trials. Earlier studies reported improved survival following surgery, though concerns remained as to whether this was at the expense of poor functional outcome among survivors. In light of these uncertainties, three European randomised controlled trials with primary end points based on functional outcome have recently been completed: DECIMAL (decompressive craniectomy in malignant middle cerebral artery infarcts)89; DESTINY (decompressive surgery for the treatment of malignant infarction of the middle cerebral artery)90; and HAMLET (hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial).91

In DECIMAL, there was a 53% absolute risk reduction in mortality at 6 months in the surgical group treated within 30 h of stroke as compared to the control group (standard therapy), which was statistically significant. Six month functional outcome data (modified Rankin Scale (mRS) ≤3) also favoured the surgery group (25% vs 5.6%), though this did not reach statistical significance due to early termination of the trial because of slow recruitment and the observed difference in mortality. The results did, however, suggest that the significant benefit on survival did not come at the expense of increased dependency, though it should be noted that none of the patients made a complete recovery (mRS ≤1). Subgroup analysis suggested that young age was associated with better outcome in the surgery group.

Despite favouring surgery, DESTINY also failed to demonstrate significance in improved functional outcome (mRS ≤3) at 6 months (47% vs 27%). The study planned to stop enrolment once significance was reached for 30 day mortality, until 6 month outcome data became available. However, sample size projections at this time suggested that it would not be possible to recruit enough patients to achieve significance for the primary end point of functional outcome. In light of this, and the published results of a pooled analysis of all three trials,92 the study was terminated in April 2006.

HAMLET extended the time window to recruit patients within 96 h from onset. Again there was improved survival in the surgical group with an absolute risk reduction of 38%, though this appeared to be at the expense of increased dependency. There was no improvement in good outcome (mRS ≤3), which was in fact exactly the same in both treatment groups, though functional outcome was improved in those patients treated within 48 h.

Data from a pooled analysis of these three trials have recently been published,92 including only the patients randomised and treated within 48 h (therefore excluding 34 patients in HAMLET). At the time of the analysis, HAMLET was still ongoing, though DECIMAL and DESTINY had been terminated. Mortality at 12 months was significantly improved with an absolute risk reduction (ARR) of 50.3% (odds ratio (OR) 0.1, 95% confidence interval (CI) 0.04 to 0.27) in the surgery group. Favourable outcome (mRS ≤3) was also significantly improved with an ARR 22.7% (OR 0.33, 95% CI 0.13 to 0.86). The numbers needed to treat for outcome measures of survival and favourable outcome were therefore 2 and 4, respectively. However, despite the increase in favourable outcome in the surgery group, it should be noted that the significantly reduced mortality did come at the expense of an increase in moderate disability (mRS 4) from 2% to 31%, though severe disability (mRS 5) was not increased. The distribution of mRS at 12 months between the two groups is illustrated in figure 3.

Figure 3

Distribution of the 12 month modified Rankin Scale (mRS) in patients treated with hemicraniectomy compared with those managed conservatively. Adapted from Vahedi K, et al.92

Patients considered for surgery should also be managed according to general management principles common to all patients with acute ischaemic stroke. The use of thrombolysis treatment should not deter from neurosurgical referral in appropriate patients in light of its short half life, and potential for reversal if necessary. Despite the potential benefits of decompressive surgery, unanswered questions remain. None of the three randomised trials included patients above the age of 60, and so these results should not be generalised to the older population. Cerebral oedema following MCA infarction commonly manifests at or beyond 48 h, though there are no data to support surgical decompression after this time. The National Institute for Health and Clinical Excellence (NICE) have issued guidance on patients with MCA infarction who should be considered for hemicraniectomy,93 and criteria are outlined in box 1. The recommendation states that patients should be referred within 24 h of symptom onset, and treated within a maximum of 48 h. Although there is no evidence to support improvement in functional outcome beyond this time, there may be improved survival at the expense of increased dependency. Treatment decisions in these patients are therefore much more difficult, and involve careful discussion with neurosurgeons and family members, considering any wishes the patient may have held relating to survival and dependency.

Box 1 National Institute for Health and Clinical Excellence (NICE) criteria for consideration of hemicraniectomy

  • Aged 60 years or under.

  • Clinical deficits suggestive of infarction in the territory of the middle cerebral artery (MCA) with a score on the National Institute of Health Stroke Scale (NIHSS) of above 15.

  • Decrease in the level of consciousness to give a score of 1 or more on item 1a of the NIHSS.

  • Signs on computed tomography of an infarct of at least 50% of the MCA territory, with or without additional infarction in the territory of the anterior or posterior cerebral artery on the same side, or infarct volume >145 cm3 as shown on diffusion weighted magnetic resonance imaging.

Summary

Malignant MCA infarction is associated with extremely high mortality and poor functional outcome. General measures to reduce ICP, such as head elevation and the use of osmotic agents, can effectively reduce cerebral oedema following massive hemispheric stroke, though the effects are short lived and data do not demonstrate improved outcomes. However, these measures may prove effective in the short term when more definitive treatment such as decompressive surgery is awaited. Hemicraniectomy for malignant MCA infarction is not a new concept, though only recently have randomised data been available. Surgery has proved to be effective in selected patients at significantly reducing mortality, which does not appear to be at the expense of increased dependency. The pooled analysis data showed that surgical intervention within 48 h doubled the chance of a good outcome, though questions still remain regarding whether the benefits persist beyond this time, and the role in older patients and those with other comorbidity. Surgery in these cases may improve survival, though at the expense of increased dependency, with potential impact and strain upon resources for post-acute care. Further studies are therefore needed to clarify these areas of uncertainty.

Multiple choice questions (true (T)/false (F); see page 242 for answers)

1. Established predictors of malignant MCA infarction include:

  1. A prior history of hypertension

  2. Reduced level of consciousness on admission

  3. >50% MCA territory involvement on computed tomography

  4. Elevated body temperature

  5. Advancing age

2. Regarding malignant MCA infarction:

  1. Clinical manifestations result from the effects of space occupying oedema

  2. Neurological deterioration typically occurs after the first week of stroke onset

  3. Transtentorial herniation is the most common cause of death

  4. Younger patients are generally more susceptible

  5. Mortality approaches 20% when treated conservatively

3. Cytotoxic oedema:

  1. Appears earlier than vasogenic oedema

  2. Relies upon breakdown of the BBB

  3. Does not contribute significantly to overall brain swelling

  4. Results from failure of cellular energy dependent primary active transport systems

  5. Is characterised by movement of fluid into the interstitial space

4. Regarding the treatment of malignant MCA infarction:

  1. Steroids improve functional outcome and mortality at 12 months

  2. Mannitol reduces ICP by generating an osmotic gradient across the BBB

  3. Hypertonic saline is a more potent osmotic agent than mannitol

  4. Antiplatelet agents should be withheld

  5. Surgical decompression should be considered only when medical therapy fails

5. Hemicraniectomy for malignant MCA infarction:

  1. Significantly reduces mortality at 12 months

  2. Does not improve favourable outcome (mRS <4) at 12 months

  3. Is more beneficial in patients aged >60 years

  4. Should be avoided within the first 48 h of stroke onset

  5. Is of no benefit in patients with dominant hemisphere infarction

Key learning points

  • Malignant MCA infarction describes the rapid neurological deterioration due to the effects of space occupying oedema following MCA territory stroke.

  • Other causes of early neurological deterioration following ischaemic stroke should also be considered.

  • Malignant MCA infarction carries a very poor prognosis, and early detection is essential if surgical intervention is to be considered.

  • Osmotherapy has limited value unless followed by definitive surgical treatment.

  • Hemicraniectomy improves both survival and functional outcome in selected patients.

Current research questions

  • Factors which determine the extent of ischaemic cerebral oedema in individual patients are unclear.

  • Mannitol is used widely for the treatment of cerebral oedema, though data regarding its use in the context of ischaemic stroke are lacking.

  • The role of hemicraniectomy in patients >60 years, and beyond 48 h of stroke onset, is unclear.

Key references

▶ Hacke W, Schwab S, Horn M, et al. ‘Malignant’ middle cerebral artery territory infarction. Arch Neurol 1996;53:309–15.

▶ Qureshi AI, Suarez JI, Yahia AM, et al. Timing of neurologic deterioration in massive middle cerebral artery infarction: a multicenter review. Crit Care Med 2003;31:272–7.

▶ Sacco RL. Risk factors and outcomes for ischaemic stroke. Neurology 1995;45(Suppl 1):10–14.

▶ Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol 2007;6:215–22.

▶ National Collaborating Centre for Chronic Conditions. Stroke: national clinical guideline for diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). London: Royal College of Physicians, 2008.

Answers

  1. A (T); B (T); C (T); D (T); E (F)

  2. A (T); B (F); C (T); D (T); E (F)

  3. A (T); B (F); C (T); D (T); E (F)

  4. A (F); B (T); C (T); D (F); E (F)

  5. A (T); B (F); C (F); D (F); E (F)

References

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Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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