Early neurological deterioration in acute ischaemic stroke: predictors, mechanisms and management

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1 1 Southwarwikshire Hospital, Warwik, UK; 2 Integrated Mediine, Glenfield Hospital, Leiester, UK; 3 Cerebrovasular Mediine, University Hospitals of Leiester NHS Trust, Leiester, UK Correspondene to: Dr B Thanvi, Southwarwikshire Hospital, Lakin Road, Warwik CV34 5BW, UK; bthanvi@ hotmail.om Reeived 13 November 2007 Aepted 27 April 2008 Early neurologial deterioration in aute ishaemi stroke: preditors, mehanisms and management B Thanvi, 1 S Treadwell, 2 T Robinson 3 ABSTRACT Early neurologial deterioration (END) in aute ishaemi stroke is a ommon event. The underlying mehanisms are heterogeneous. The linial preditors of END inlude severity of the initial stroke, large vessel olusion, diabetes mellitus, hypotension, and atrial fibrillation. Serial observations and detailed assessment by the trained staff in speialised stroke units are key to the suessful management of these patients. Advanes in brain and vasular imaging have provided insight into the underlying mehanisms, enabling liniians to use preventative and therapeuti interventions speifially targeted at them, though several questions still remain unanswered. END has potentially serious onsequenes on the short term (morbidity and death) and long term (reovery from stroke) outomes for the patient. Therefore, attempts to prevent and treat END should be made promptly and aggressively. Worsening of aute stroke early in its ourse (within h of its onset) is a ommon ourrene and has potentially serious short term and long term onsequenes for the patient. The underlying mehanisms are mostly neurologi as opposed to the worsening in the later part of stroke when systemi fators (for example, infetion, eletrolyte disturbanes, myoardial ishaemia, venous thromboembolism, et) tend to play a greater role. 1 In primary intraerebral haemorrhage, worsening is often related to ontinuous bleeding whereas reurrene of bleeding and vasospasm aount for most of the worsening in aneurysmal subarahnoid haemorrhage. In ishaemi stroke, several possible mehanisms exist that an lead to worsening. The issues surrounding the use of terminology, role of potential preditors and underlying mehanisms, and management of early worsening in ishaemi stroke shall be disussed. TERMINOLOGY One of the issues in the field of researh in early neurologi deterioration (END) has been the lak of a standard definition of deterioration or worsening as used here. Various terms, suh as progressive stroke, stroke in evolution, and stroke in progression have been used. In one of the earlier studies, neurologi worsening was determined to be present if worsening of the neurologi ondition, inluding onsiousness level, was observed by trained neurologists and nurses at and after admission to the stroke unit. 2 The European Cooperative Aute Stroke Study (ECASS) I group diagnosed early progression when there was a derease of two or more points in onsiousness or motor power or a derease of three or more points in speeh sore in the Sandinavian Neurologial Stroke sale between baseline and 24 h after. 3 Tei et al used the definition of deterioration as a derease of one or more points in the Canadian Neurologial Sale in total or partial anterior irulatory infarts and posterior irulatory infarts or one or more points on the Rankin Sore in launar infarts. 4 A reent study used an inrease in the National Institute of Health Stroke Sore (NIHSS) by two or more points (or stroke related death) between admission and day 5 as the riterion for END. 5 The time of first assessment after initial stroke onset may have an important bearing on the frequeny of END in hospitalised patients, as some of the patients seen very early after stroke may still be going through their natural worsening and would not have been inluded had they been admitted and assessed late after their stroke had stabilised. HOW COMMON IS END? The inidene of END in ishaemi stroke among hospitalised patients varies widely in different studies. In a reently published Australian study, 19% of aute stroke patients had END. 5 Inidene was greater in haemorrhagi stroke subtype than in non-haemorrhagi subtype (22% vs 7%). In the Harvard Cooperative Stroke Registry that inluded haemorrhagi and non-haemorrhagi strokes, early worsening was noted in,20% of patients. 6 In the Barelona Stroke Registry of 3577 onseutive patients hospitalised with stroke (all types), 37% showed END. 7 Rates of 29% and 25%, respetively, were reported for all aute strokes in Swiss 2 and Japanese 4 studies. In a study that exluded haemorrhagi strokes, 256 out of 1964 (13.0%) onseutive patients admitted within 4 h of the onset of aute erebral ishaemi symptoms had an inreased sore of one point or more on the NIHSS sale after h. 8 Aording to the authors, a lower frequeny of END in this study ould partly be explained by the inlusion of 18 patients with transient ishaemi attaks. Similar figures (16.1%) have been reported in a reent study. 1 It ould be argued that the availability of modern treatment (for example, thrombolysis and interventional reanalisation proedures) and stroke units might aount for the lower frequeny in the reent studies. The differenes in the time sale of assessments after aute stroke, diagnosti riteria used for END, and the ase mix of stroke patients ould aount for the wide variations reported in the studies. Even among ishaemi strokes, subtypes differ in the rates of END Postgrad Med J: first published as /pgmj on 2 Otober Downloaded from on 7 July 2018 by guest. 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2 Table 1 Preditors of early neurologial deterioration in ishaemi stroke Clinial preditors Radiologial preditors Initial stroke severity Large vessel olusion History of diabetes Hypodensity.33% in the MCA mellitus territory? Low blood pressure Hyperdense MCA sign on brain CT? Raised blood pressure Cerebral oedema on early brain CT Launar infartion Atrial fibrillation MCA, middle erebral artery. PREDICTORS OF END Several studies have looked into the linial and radiologial fators that ould possibly predit END in aute stroke (table 1). Age, gender, and pre-stroke level of independene do not generally appear to be signifiant risk fators for END, 3 5 though age was reognised as a risk fator for END in some studies. 10 Initial stroke severity inreases the risk of END. In a study to determine the value of initial NIHSS sore for risk stratifiation in ishaemi stroke, patients with an initial NIHSS (7 experiened lower frequeny of worsening (14.8%) than those with a sore.7 (65.9%), with a dihotomy in early outome surrounding an initial NIHSS sore of A redued level of onsiousness on admission is assoiated with greater END. 1 4 Severe strokes were independently related to the greater frequeny of worsening in another study. 4 Different subtypes of ishaemi strokes differ in the rates of END, with non-ardioemboli strokes being more likely to deteriorate than ardioemboli, and launar types more than the non-launar types Also, signifiantly more patients (67% vs 8%) with total anterior irulation strokes worsen than those with partial anterior irulation stroke. 4 5 Hyperglyaemia is noted on admission in approximately one third of patients with stroke and is assoiated with poor outomes after ishaemi stroke, inluding among patients treated with thrombolyti agents High serum gluose values and history of diabetes have been assoiated with END In a ase ontrolled study, previous history of diabetes along with elevated admission systoli blood pressure predited END. 18 Persistent hyperglyaemia during the first 24 h after stroke independently predited expansion of the volume of ishaemi infart and poor neurologial outomes. 19 The detrimental effets of hyperglyaemia have been attributed to tissue aidosis seondary to anaerobi glyolysis, lati aidosis, free radial prodution, disruption of the blood brain barrier, the development of brain oedema, and inreased risk of hemorrhagi transformation Hyperglyaemia may be marker of a more severe stroke. 23 It is not known whether treatment of hyperglyaemia in aute stroke has a benefiial effet on patient outome. In the reently published UK Gluose Insulin in Stroke Trial (GIST-UK), gluose potassium insulin infusion in patients with hyperglyaemia in the aute stroke setting was assoiated with a redution in blood gluose and blood pressure, but there was no signifiant effet on the 90 day mortality. 24 However, the study was underpowered to reah a definitive onlusion regarding the mortality outome. A history of elevated admission systoli blood pressure along with diabetes mellitus has been suggested to predit early deterioration. 18 The independent role of hypertension as a preditor of END has not been established. On the ontrary, it is suggested that the rates of neurologial worsening, poor neurologial outomes, or death inrease with a baseline systoli blood pressure,100 mm Hg or a diastoli blood pressure,70 mm Hg. 25 The urrent stroke guidelines, therefore, do not advise treatment of hypertension in aute stroke, exept when thrombolysis is ontemplated or in the presene of extremely severe hypertension. It is not lear whether there are high and low thresholds of optimal blood pressures in ishaemi stroke. Three ongoing studies Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS), Effiay of Nitri Oxide in Stroke (ENOS), and Continue or Stop post Stroke Antihypertensives Collaborative Study (COSSACS) aim to provide an answer to the blood pressure dilemma in aute stroke The presene of large vessel olusion has been reognised as a major independent risk fator for END in several studies In a study of early magneti resonane imaging (MRI) and outomes of patients with ishaemi stroke,,10% of patients eligible for aute reperfusion therapy exluded on the basis of mild or rapidly improving symptoms showed END with infart expansion within 48 h. 30 Authors omment that persisting large vessel olusion substantially inreases risk of END. Sequential angiographi hanges in patients with neurologi worsening show progression of arterial stenosis. 31 Interestingly, a history of prior transient ishaemi attaks is negatively related to END. 2 Sine severe stenosis is assoiated with a greater risk of transient ishaemi attaks, it is possible that mehanisms other than embolisation may operate for END in vessel olusion. Atrial fibrillation and high serum urea have also been shown to inrease risk of END. 5 Extent of hypodensity.33% in the middle erebral territory, hyperdense middle erebral artery sign, and brain swelling on omputed tomography (CT) san at 24 h are assoiated with END. 3 These may simply reflet severe initial stroke. MECHANISMS OF END Several mehanisms have been proposed to explain END in aute ishaemi stroke. They inlude failure of ollateralisation, lot progression, reurrent (loal or remote) stroke, raised intraranial pressure, seizures, and haemorrhagi transformation. Advanes in the brain and vasular imaging tehniques have provided great insight into their role in END in aute stroke. Failure of ollaterals Olusion of major erebral vessels is one of the most important independent preditors of END. Vasular olusion leads to distal hypoperfusion with its potential to ompromise perfusion of the affeted region unless effetive ollateral irulation develops. Development of ollaterals appears to be the mehanism underlying transient ishaemi attaks and rapid reovery from an ishaemi stroke. 32 Diabeti miroangiopathy and hroni hypertension 33 impair mirovasular funtion, reduing the potential for ollateral development. This leads to redued oxygen delivery and regional metaboli disturbanes, whih may aggravate ellular damage by enhaning brain oedema and free radial injury Insuffiient ollaterals with the adverse metaboli onsequenes on the ishaemi penumbra appear to be the most ommon mehanism for END. 35 Initially, linial worsening is due to synapti dysfuntion with preserved ell membrane integrity and is potentially reversible with vessel reanalisation. 35 Serial transranial Doppler studies may be useful for haemodynami evaluation in aute stroke 36 and large vessel pateny an be evaluated by duplex ultrasound, magneti resonane angiography, and CT angiography. Postgrad Med J: first published as /pgmj on 2 Otober Downloaded from on 7 July 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

3 Clot progression In the past, END in aute ishaemi stroke had been attributed to lot progression, 37 though this had never been demonstrated. Reent studies of early MRI in aute stroke have shown large vessel olusion and failure of ollaterals rather than lot progression as the main mehanism of END. Hypoperfusion due to oluded vessels may impair washout of distal emboli and the two may at synergistially to ause END. 32 Reurrent stroke Patients with aute ishaemi stroke are at a high risk of reurrent stroke in the first week. However, most of the reurrent strokes deteted on diffusion weighted MRI sans do not produe linial defiit. 40 Weimer et al 8 reported reurrent erebral ishaemia as the ause of END in 11.3% of ases. Reurrent embolism an our in the original region or in a remote loation. Transranial Doppler an detet miroemboli signals and may be useful for identifying patients at risk of early reurrent stroke. 41 Cerebral oedema Raised intraranial pressure aounts for,19% of ases of early deterioration in ishaemi stroke. 8 The overall risk of brain swelling in patients with anterior irulation stroke is low and is estimated to be 10 20%. 42 In patients with an oluded stem of the middle erebral artery, erebral oedema tends to appear 4 days after the onset of stroke. The term malignant has been used to desribe brain oedema in patients with a large territorial infart that swells within 24 h, ausing signs of brain herniation. 43 Clinial features suh as a deteriorating level of onsiousness, bilateral ptosis and involvement of the nondominant hemisphere may suggest a high risk of deterioration. In middle erebral infarts, NIHSS sore.20, involvement of two thirds or more of the artery on initial brain imaging, onomitant anterior and posterior erebral artery infartion, and lesion volume.145 ml on diffusion weighted imaging san predit evolution to fatal erebral oedema. 44 Cerebral oedema in ishaemi stroke tends to be ytotoxi and does not respond to osmoti diuretis. Haemorrhagi transformation Haemorrhagi transformation in ishaemi stroke is ommon and ranges from small asymptomati petehiae to a large haematoma with pressure effets. Symptomati transformation ours only in 0.6% of patients treated with supportive are, whereas the inidene is higher in those treated with intravenous reombinant tissue plasminogen ativator (rt-pa) (6%), mehanial emboletomy (8%), and intra-arterial fibrinolytis Thrombolysis related transformation has been lassified into four types: haemorrhagi infartion types 1 and 2, and parenhymal haematoma types 1 and Haemorrhagi infartion is defined as small petehiae along the margins of the infart or more onfluent petehiae within the infarted area, but without spae oupying effet. Parenhymal haematoma is defined as blood lot with spae oupying effet. Only parenhymal haematoma type 2 (large haematoma.30% of ishaemi lesion volume) are onsidered to be assoiated with adverse outome. 49 Haemorrhagi infartion 1 and 2 may represent reperfusion injury (and suessful reanalisation) leading to redution in infart size and improved linial outome. 48 The risk fators for thrombolysis related intraerebral haemorrhage inlude old age, severe initial stroke, high serum gluose values, and signs of mass effet on pre-treatment imaging. 50 Though thrombolysis with rt-pa inreases risk of haemorrhage, it requires 100 patients to be treated with rt-pa to get one signifiant adverse outome. 51 Seondary haemorrhage aounted for,10% of ases of END in one study. 8 Re-olusion of a reanalised artery With the advent of thrombolysis and mehanial reanalisation proedures in stroke treatment, re-olusion has been inreasingly reognised as a ause of END. 32 Early re-olusion ours in 34% of rt-pa treated patients with any initial reanalisation, aounting for two thirds of deteriorations following improvement. 51 Stroke severity, partial reanalisation after rt-pa, and ipsilateral severe arotid artery disease independently predit reolusion after rt-pa indued reanalisation of the middle erebral artery. 52 Real-time use of transranial Doppler in suh patients may identify re-olusion and help to predit whih patients will benefit from intra-arterial thrombolysis or mehanial emboletomy. 51 Seizures Seizures are ommon in large ortial ishaemi infarts and may aount for END in,5% of patients with ishaemi strokes. 53 Seizures often ause only temporary worsening, though prolonged partial seizures an lead to persistent worsening. 54 Non-onvulsive seizures, diffiult to detet linially and requiring eletroenephalography (EEG) to diagnose, may aount for worsening in some ases. 55 MANAGEMENT OF END Given the signifiantly high frequeny of END, all patients with aute stroke should be admitted to speialised stroke units with trained multidisiplinary staff apable of arrying out detailed and frequent assessments of the general and neurologial status of patients. Those patients with risk fators for END and those with overt signs of deterioration should be admitted to the high dependeny or intensive are areas. Sine there are several auses of END, no single intervention is likely to be effetive for all patients. Good supportive are and attention to temperature, oxygenation, hydration, interurrent infetions, thromboprophylaxis, positioning, pressure areas, bowel and bladder are, et, is essential to the are of all patients with aute stroke. Speifi interventions for prevention and treatment of END depend upon the underlying mehanism. A detailed work-up with serial neurologial assessments using NIHSS and appropriate seletion of diagnosti tests for example CT, MRI, MR angiography, duplex and transranial Doppler, and EEG is required to eluidate the ause(s) of END. Large vessel olusion and failure of ollaterals is the most ommon mehanism of END. Reanalisation interventions for example, thrombolysis with rt-pa or mehanial emboletomy in appropriate ases may redue frequeny of END, though diret evidene for this is laking. In a series of patients where thrombolysis was not given in view of rapidly improving symptoms or minor symptoms, END ourred in 38% of patients with large vessel olusion but in only 3% of those with no olusion. 30 In future, general availability of penumbral imaging ombined with vasular imaging might help in seleting patients who would benefit from late reanalisation therapies. 35 An alternative approah is ollateral augmentation. In patients where a drop in blood pressure or redued erebral perfusion is the likely mehanism of deterioration, head down position and pressor therapy (with fluids or pressor agents) may Postgrad Med J: first published as /pgmj on 2 Otober Downloaded from on 7 July 2018 by guest. Proteted by opyright. 414 Postgrad Med J 2008;84: doi: /pgmj

4 Box 1: Some of the unanswered questions in relation to the early neurologial worsening in aute stroke Does treatment of hyperglyaemia in aute stroke improve survival? What is the optimum ontrol of blood pressure in aute stroke? What is the ideal method for improving ollateral irulation in aute stroke? How to redue the risk of potentially detrimental haemorrhagi transformation (parenhymal haematoma) in aute stroke? What is the best medial treatment for erebral oedema in aute stroke? be appropriate. However, evidene for pressor therapy is insuffiient. In a pilot randomised trial of 15 patients with aute ishaemi stroke and.20% diffusion perfusion mismath on MRI, signifiant improvement in NIHSS, ognitive sore and volume of hypoperfused tissue (132 to 58 ml) on perfusion weighted imaging was reported in patients given phenylephrine as a pressor agent. 56 No signifiant untoward effets were observed. However, no large sale studies are available to draw definitive onlusions. In an approah to augment erebral blood flow by partial aorti obstrution using a double-balloon devie in patients with vasospasm ompliating aneurysmal subarahnoid haemorrhage, Lylyk et al reported improvement in neurologial defiits. 57 In the Early use of Existing Preventive Strategies of Stroke (EXPRESS) trial, early initiation of preventive treatments after transient ishaemi attaks or minor stroke was assoiated with an 80% redution in the risk of early reurrent stroke. 58 Antiplatelet agents are used to redue reurrent embolism in ishaemi stroke. A ombination of aspirin and dipyridamole is superior to aspirin alone. 59 Clopidogrel an be used in patients with genuine aspirin allergy. An ongoing study is aiming to ompare the effiay of aspirin plus dipyridamole versus lopidogrel in stroke prevention. 60 A reent study suggested superiority of ombination of aspirin and lopidogrel over aspirin alone in reduing stroke reurrene (7% vs 10.8%) when given early after a transient ishaemi attak or minor stroke. 61 The authors omment that the benefit was not negated by the inreased risk of haemorrhage with the ombination treatment. Antioagulation with heparin is sometimes used in ishaemi stroke to redue reurrent embolism, though evidene for its effiay is not proven and safety onerns exist. The International Stroke Trial tested two doses (5000 U/day or U/day) of subutaneously administered heparin within 48 h of stroke. 62 Although heparin was effetive in lowering the risk of early reurrent stroke, an inreased rate of bleeding ompliations negated this benefit.. The reommendation from urrent guidelines from the Amerian Heart Assoiation/ Amerian Stroke Assoiation 63 says urgent antioagulation with the goal of preventing early reurrent stroke, halting neurologial worsening, or improving outomes after aute ishaemi stroke is not reommended for treatment of patients with aute ishaemi stroke. There is no evidene for use of glyoprotein IIb/IIIa inhibitors in ishaemi stroke. Cerebral oedema in ishaemi stroke is ytotoxi and is unresponsive to steroids, hyperventilation, and osmoti agents. Deompressive surgery, inluding hemiranietomy and durotomy with temporal lobe resetion, may be onsidered in seleted patients with pronouned ishaemi brain swelling. 64 In patients with malignant middle erebral artery infartion, deompressive surgery undertaken within 48 h of stroke onset redues mortality and has a favourable effet on the funtional outome. 65 No intervention is urrently available to redue the risk of haemorrhagi transformation exept that patients for thrombolysis should be appropriately seleted. Spae oupying haematoma resulting from thrombolysis may require neurosurgial evauation. There is no evidene for prophylati use of antiepilepti agents. Patients with evident seizures should be treated with antiepilepti agents. CONCLUSION Early neurologial deterioration in ishaemi stroke is ommon and is assoiated with poor outome and death. Development of stroke units has evidently improved outomes in aute stroke and it is possible, though not proven, that reent reports of deline in the rates of early worsening may partly be attributed to the inreasing are in stroke units. Reognition of the preditors of early worsening may help in seleting patients for admission to the high dependeny units equipped with intensive monitoring and treatment of these ill patients and prompt initiation of appropriate therapy. Prompt institution of antithromboti treatment may help in reduing risk of reurrent stroke. Reognition and appropriate management of raised temperature, hyperglyaemia, hypotension, atrial fibrillation, and large vessel olusion may prevent early worsening and improve patient outome. Despite advanes in the treatment of aute stroke, several questions remain unanswered (box 1). Hyperglyaemia is a reognised preditor of early worsening but the evidene for a benefiial effet of treating hyperglyaemia in aute stroke on outomes is laking. Similarly, diret evidene for reduing frequeny of early worsening with reanalisation interventions for example, thrombolysis with rt-pa or mehanial emboletomy is not available. Blood pressure management in aute stroke is still a matter of debate and is a subjet of ongoing studies (COSSACS, ENOS). Craniotomy for large ishaemi infartions assoiated with erebral oedema is appliable for Key learning points Worsening of aute stroke early in its ourse is a ommon ourrene and is assoiated with inreased morbidity and mortality. The underlying mehanisms inlude failure of ollaterals, lot progression, reurrent (loal or remote) stroke, raised intraranial pressure, seizures, and haemorrhagi transformation of the ishaemi infart. Clinial preditors of early worsening inlude severity of initial stroke, large vessel olusion, diabetes mellitus, hypotension, and atrial fibrillation. Radiologial preditors inlude extent of hypodensity.33% in the middle erebral territory, hyperdense middle erebral artery sign and brain swelling on CT san at 24 h. Modern imaging tehniques are very useful for the assessment, risk stratifiation, and management of these patients. As the patient s ondition an deteriorate rapidly, urgent and aggressive approah to diagnose, assess and treat these patients is warranted. Postgrad Med J: first published as /pgmj on 2 Otober Downloaded from on 7 July 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

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6 59. The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after erebral ishaemia of arterial origin (ESPRIT). Lanet 2006;367: Diener HC, Sao R, Yusuf S, Steering Committee for the PRoFESS Study Group. Rationale, design and baseline data of a randomized, double-blind, ontrolled trial omparing two antithromboti regimens (a fixed-dose ombination of extendedrelease dipyridamole plus ASA with lopidogrel) and telmisartan versus plaebo in patients with strokes: the Prevention Regimen for Effetively Avoiding Seond Strokes Trial (PRoFESS). Cerebrovas Dis 2007;23: Kennedy J, Hill MD, Rykborst KJ, et al. Fast Assessment of Stroke and Transient ishaemi attak to prevent Early Reurrene (FASTER): a randomised ontrolled pilot trial. Lanet Neurol 2007;6: International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subutaneous heparin, both, or neither among 9435 patients with aute ishaemi stroke. Lanet 1997;349: Transendental meditation and hypertension A 58-year-old woman was referred to our lini for advie on the management of hypertension. As part of her pre-lini assessment a 24 h ambulatory blood pressure measurement was performed (fig 1). This revealed a striking dip in blood pressure at around 17:00 with her systoli and diastoli measurements both being lower than when she was asleep. On review in lini it transpired that this dip orresponded to the patient pratising transendental meditation. There is some evidene to suggest that regular transendental meditation may redue blood pressure in hypertensive patients, although at around 5/3 mm Hg, 1 this is onsiderably less than the striking, aute redution in blood pressure seen in our patient. J W Dear, K Gough, D J Webb Cardiovasular Risk Clini, Western General Hospital, Edinburgh, UK Correspondene to: Dr J Dear, Cardiovasular Risk Clini, Western General Hospital, Edinburgh, UK; james.dear@ed.a.uk 63. Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ishemi stroke: a guideline from the Amerian Heart Assoiation/ Amerian Stroke Assoiation Stroke Counil, Clinial Cardiology Counil, Cardiovasular Radiology and Intervention Counil, and the Atherosleroti Peripheral Vasular Disease and Quality of Care Outomes in Researh Interdisiplinary Working Groups: the Amerian Aademy of Neurology affirms the value of this guideline as an eduational tool for neurologists. Cirulation 2007;115:e Shwab S, Steiner T, Ashoff A, et al. Early hemiranietomy in patients with omplete middle erebral artery infartion. Stroke 1998;29: Vahedi K, Hofmeijer J, Juettler E, et al, for the DESTINY, and HAMLET Investigators. Early deompressive surgery in malignant infartion of the middle erebral artery: a pooled analysis of three randomised ontrolled trials. Lanet Neurol 2007;6: Figure 1 Images in mediine 24 h ambulatory blood pressure measurement. Competing interests: None. Patient onsent: Obtained. Postgrad Med J 2008;84:417. doi: /pgmj REFERENCE 1. Anderson JW, Liu C, Krysio RJ. Blood pressure response to transendental meditation: a meta-analysis. Am J Hypertens 2008;21: Postgrad Med J: first published as /pgmj on 2 Otober Downloaded from on 7 July 2018 by guest. Proteted by opyright. Postgrad Med J 2008 Vol 84 No