Ischemic Stroke - Springer Link

Clinical Neuroradiology

Review Article

Ischemic Stroke – Serious, but not Hopeless A View from the Heidelberg School of Neuroradiology Rüdiger von Kummer1, Joanna Wardlaw2

Abstract Patients at risk of disabling stroke or death from stroke may present asymptomatic, with transient ischemic attack or minor stroke, or with acute disabling stroke. In all these patients, the diagnostic work-up of vascular and brain pathology is crucial to determine the immediate risk of brain damage and permanent disability. Neuroradiology has the means to quickly gain this information and thus to guide stroke patient management. Key Words: Cerebral Ischemia · Ischemic Stroke · Stroke Imaging · CT · MRI Clin Neuroradiol 2008;18:37–44 DOI: 10.1007/s00062-008-8004-x

Zerebrale Ischämie – ernst aber nicht hoffnungslos. Eine Sicht der Heidelberger Neuroradiologieschule Zusammenfassung Patienten mit dem hohen Risiko für eine Behinderung oder Tod durch Schlaganfall werden eingewiesen asymptomatisch, nach transienter zerebraler Ischämie, mit geringen oder auch bedrohlichen, akut behindernden Symptomen. Bei allen diesen Patienten entscheidet die sofortige Diagnostik der arteriellen und zerebralen Pathologie über die Chancen, einen bleibenden Hirnschaden mit lebenslanger Behinderung zu vermeiden. Die Neuroradiologie hat heute die Möglichkeit, alle wesentlichen Informationen rasch einzuholen, und kann so eine gezielte und erfolgreiche Behandlung der zerebralen Ischämie ermöglichen. Schlüsselwörter: Zerebrale Ischämie · Schlaganfall · Multimodales Imaging · CT · MRT

Introduction Ischemic stroke may cause severe disability and death, if not prevented or treated in time. This article outlines the important role of neuroradiology in acute stroke management. When examining asymptomatic patients at risk of stroke, patients with transient ischemic attacks (TIAs), and patients with completed disabling stroke, imaging of the brain and supplying vessels is crucial. Brain, vascular and functional imaging have the capability to assess individual risks and chances for recovery by distinguishing stroke from stroke mimics, by identifying the type and often also the cause of stroke, and may help to differentiate irreversibly damaged tissue from areas 1

that may recover thus guiding emergency management and subsequent specific treatment, and may thus help to predict outcome. Vascular imaging may identify the site and cause of arterial obstruction, and identifies patients at high risk of stroke recurrence for specific preventative treatments. Functional imaging can directly assess patterns of brain perfusion disturbance and the capacity of cerebral perfusion reserve thus identifying arterial obstruction causing critical hypoperfusion. Clinical Efficacy of Diagnostic Imaging In deciding when and how to order imaging investigations, it should be considered, to what extent the imaging results will affect the patient’s care and what type of

Department of Neuroradiology, Technical University of Dresden, Germany, Department of Clinical Neurosciences, The University of Edinburgh, UK.

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Received: November 14, 2007; accepted: December 7, 2007

Clin Neuroradiol 2008 · No. 1 © Urban & Vogel

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Kummer R von, Wardlaw J. Ischemic Stroke

imaging modality the patient can tolerate. Diagnostic imaging in acute stroke may impact on different levels of diagnosis and management, but should be used judiciously [1]. Brain imaging may reduce health-care costs by preventing disability and death after stroke through correct diagnosis of patients and exclusion of stroke mimics, resulting in the use of the appropriate treatment for patients with acute neurologic deficit from other causes, and the use of specific treatments in patients with stroke,

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e.g., reperfusion strategies. Diagnostic imaging must be accurate in detecting stroke pathology at the time when a specific treatment is effective, e.g. within 3 h of stroke onset, should provide reliable images, and should be technically feasible and safe in acute stroke patients. General Principles Stroke units should provide brain imaging on each day of the week and for 24 h per day. Acute stroke patients should have a clear priority for brain imaging compared to other patients, because time limits are so crucial. Imaging tests should be scheduled in parallel with emergency medical management and take the patient’s condition into account. Many patients with major, potentially disabling stroke can be managed on the basis of computed tomography (CT), and a substantial proportion (up to 45%) of these patients may not be able to tolerate magnetic resonance (MR) examination because of their medical condition [2–4]. In many patients with moderate to severe acute disabling stroke, diagnostic brain imaging must be performed without delay on arrival at a hospital so that treatment can be started immediately. Diagnostic brain imaging is important also in patients with TIA of whom up to 10% will

Figures 1a to 1c. A 57-year-old woman with arterial hypertension and smoking habit had a checkup with carotid Doppler ultrasound. She was sent to MRI, because the right common carotid artery was missing (a). To assess the clinical relevance of common carotid artery occlusion, we obtained a time-to-peak map on MRI after contrast bolus injection (b). Contrast inflow was delayed into the right ACA and MCA territory. To further evaluate the risk of stroke, we measured the cerebral perfusion reserve using the blood oxygen level-dependent (BOLD) contrast after short periods of breath holding (c). The cerebral perfusion reserve was not impaired, because common carotid artery occlusion was fully compensated by collateral blood flow.



suffer stroke within the next 48 h [5]. Immediate access to imaging on arrival at hospital is facilitated by good communication with the imaging facility: stroke services including the ambulances should work closely with the imaging department to plan best use of resources. If necessary, emergency life support should be continued while the patient is being imaged, as patients (especially those with severe stroke) may become hypoxic while supine during imaging [4]. The risk of aspiration is increased in the substantial proportion of patients who are unable to protect their airway. Rapid neurologic assessment assists considerably in determining which imaging technique is likely to be most helpful and to tailor the individual imaging examination. Patients with Incidental Findings Indicating a Potential Risk of Stroke The wide availability of noninvasive vascular and brain imaging increases the chance to detect diseases associated with a risk of stroke. Among imaging findings not yet associated with obvious symptoms, but with increased risk of ischemic stroke or intracranial hemorrhage are stenoses and occlusions of brain-supplying arteries, intracranial aneurysms and arteriovenous malformations, and patterns of silent ischemic brain lesions (Figure 1). Like in patients with TIA, additional diagnostic work-up in these patients may allow to better assess the risk of stroke and help to decide whether primary prophylaxis or intervention with embolization, angioplasty, surgery, or radiation may decrease the risk of stroke to an extent that outweighs the risk of treatment. Imaging in Patients with TIA, Minor Nondisabling Stroke, and Stroke with Spontaneous Recovery Patients presenting with TIA and minor stroke are at a high risk of early recurrent stroke, of the order


of up to 10% in the first 48 h [5, 6]. One third of patients not treated with thrombolysis because of “too mild” strokes or rapid improvement were dead or disabled at the end of their hospital stay [7] (Figure 2). TIA patients need, therefore, urgent diagnostic work-up to identify treatable causes, particularly arterial stenosis and other embolic sources. Simple clinical scoring systems can be used to identify patients at particularly high risk [6]. Patients with widely varying brain pathology may present with transient neurologic deficits indistinguishable from TIA. CT detects some of these pathologies reliably (like intracerebral hemorrhage, subdural hematoma, tumors), but other conditions are better identified on MR imaging (MRI; like multiple sclerosis, encephalitis, hypoxic brain damage, etc.) while others are not vis-

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Figures 2a to 2d. A 54-year-old man was admitted because of slight dysfunction of his left hand for 2 h. The hyperdense segment of right MCA was missed on CT (a) and no specific treatment was initiated. The patient deteriorated considerably 6 h later with severe left-sided hemiparesis and impairment of consciousness. The CT 2 h after clinical deterioration showed complete hyperdensity of right MCA trunk, but subtle brain tissue hypoattenuation only (b). CTA revealed combined ICA and MCA occlusion (c). We achieved local thrombolysis of right MCA after passing the occluded ICA with a 5-F catheter through which a microcatheter could reach the thrombus within the MCA (d). The patient was discharged with a partial MCA infarction.

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ible at all, e.g., acute metabolic disturbances. Between 20% and 50% of patients with TIAs may have acute ischemic lesions on diffusion-weighted imaging (DWI), the proportion probably depending on the timing of scanning [8–10]. Patients with an acute ischemic lesion on DWI are at increased risk of early recurrent disabling stroke: 15% in-hospital risk in patients with infarction on DWI; 11% 90-day risk of disabling stroke in patients with a DWI lesion but normal MR angiography (MRA), rising to 33% within 4 days with a DWI lesion and arterial obstruction [10]. There is no evidence available yet, however, that DWI provides better stroke prediction than do clinical risk scores [11]. The risk of recurrent disabling stroke is also increased up to 38% within 90 days of TIA and in patients with infarct visible on CT [12]. The ability of DWI and T2* to identify very small ischemic lesions and hemorrhages can be particularly helpful in patients with mild nondisabling stroke in whom establishing the diagnosis of stroke on clinical grounds may be difficult because of few signs and subtle symptoms [13]. Hemosiderin deposits may be detected on MR with T2* imaging and are present in up to 5% of healthy adults and up to 60% of patients with hemorrhagic stroke. These are associated with older age, hypertension, diabetes, leukoaraiosis, lacunar stroke, and amyloid angiopathy [14]. The effect of antithrombotic and anticoagulant treatment on the risk of hemorrhagic stroke is unclear although likely to be increased. Symptomatic intracranial hemorrhage following thrombolytic therapy in ischemic stroke patients was not increased in those having cerebral hemosiderin deposits on pretreat ment T2*-weighted MRI [15]. Vascular imaging should be performed rapidly to identify patients with tight symptomatic arterial stenosis who may benefit from endarterectomy or angioplasty. Noninvasive imaging with either color-coded duplex imaging of the extracranial and intracranial arteries, CT angiography (CTA), or contrast-enhanced MRA (CEMRA) is widely available. Intraarterial angiography in suspected carotid stenosis is rarely needed when noninvasive imaging facilities are available. Noninvasive imaging is relatively risk-free, whereas intraarterial angiography has a 2–3% risk of causing a disabling stroke [16, 17]. Carotid ultrasound can visualize proximal internal carotid artery (ICA) stenosis well and can determine the degree of stenosis and plaque characteristics. MRA and CTA can also visualize carotid stenosis well. Systematic reviews and individual patient data meta-analysis indicate that CE-MRA is the most sensitive and specific of

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the noninvasive imaging modalities for carotid artery stenosis, closely followed by Doppler ultrasound, and then CTA and, lastly, non-contrast MRA [18]. Transcranial Doppler (TCD) ultrasound allows visualization of the intracerebral vessels and detection of stenosis. A disadvantage is that up to 20% of acute stroke patients do not have an adequate acoustic window for adequate visualization of the intracranial vessels [19]. This is increased in elderly individuals and certain ethnic groups, such as black individuals. The problem can be reduced considerably using ultrasound contrast agents [20–23]. Cerebrovascular ultrasound has a number of characteristics that make it suitable for the emergency stroke setting. It is fast and noninvasive and can be administered using portable machines. It is therefore applicable to patients unable to cooperate with MRA or CTA [24]. It is also more widely available worldwide. Disadvantages are that it is investigator-dependent and requires skilled operators. Further advantages include that it allows repeated measurements at the bedside. TCD allows continuous monitoring of basal cerebral arterial velocities and the study of cerebral hemodynamic responses [25]. Cerebral reactivity and cerebral autoregulation are impaired in patients with occlusive extracerebral arterial disease (particularly carotid stenosis and occlusion) who have inadequate collateral supply. This group of patients has an increased risk of recurrent stroke [26, 27]. The regional response of cerebral perfusion to short periods of breath holding can be assessed by imaging of the blood oxygen level-dependent (BOLD) effect on MRI signal. TCD is the only technique that allows detection of intracerebral emboli [28]. These are most commonly monitored in the middle cerebral artery (MCA). They are particularly common in patients with large artery disease (ICA stenosis or MCA stenosis). Their presence is a strong independent predictor of early recurrent stroke and TIA risk [29], and they have been used as a surrogate marker to evaluate antiplatelet agents [30]. TCD emboli detection can be used to detect patent foramen ovale (PFO). The sensitivity of this technique to PFO appears as good as that of transthoracic echocardiography [31]. Imaging in Patients with Acute Disabling and Progressing Stroke All patients with stroke should undergo brain and vascular imaging on arrival at hospital in order to immediately choose the appropriate treatment. Patients admitted within 3 h of stroke onset may be candidates



ating ischemic brain tissue exceeding one third of the for intravenous thrombolysis within the current license MCA territory may have less chance to benefit from [32]. They may not benefit from intravenous thrombolthrombolysis [32, 42, 43, 52, 53] (Figure 3). ysis, however, if ischemic damage is extended or intraMRI is less easily accessible and is less suited for agicranial MCA occlusion is combined with ICA occlusion tated patients or for those who may vomit and aspirate. or stenosis, probably because the agent has no chance It has the advantage that it can identify early ischemic to reach the site of occlusion [33, 34]. Patients arriving changes with DWI sequences with higher sensitivity than later may be candidates for trials testing extended time CT, and can also detect small and old hemorrhages with windows for thrombolysis or other experimental reperT2* (gradient echo) sequences. Old hemorrhages seem fusion strategies. CT combined with CTA should guide to remain visible indefinitely on gradient echo MRI [54]. routine thrombolysis; there is no evidence of any advanDWI identifies even very small ischemic brain letage for MRI [35, 36]. sions very early with good sensitivity thus confirming Plain CT is widely available, reliably identifies stroke brain ischemia as the cause of stroke, but its specificity mimics, and distinguishes acute ischemic from hemorfor ischemic brain damage is moderate. Restricted warhagic stroke, reliably identifying intracerebral hemorter diffusion is currently best explained by the shrinkrhage within the first 5–7 days [37, 38]. Immediate CT age of extracellular space and cellular edema that can scanning is the most cost-effective strategy for imaging be observed at cerebral blood flow levels between 20 acute hospital-admitted patients with stroke [39]. CT is and 30 ml per 100 g and minute [55–57]. DWI may show not sensitive for old hemorrhage. Overall, CT is less senhyperintensities that may be mistaken for acute stroke sitive, but as specific, for early ischemic changes as MRI. following epileptic fits, in multiple sclerosis, encephaTwo thirds of patients with moderate to severe stroke litis, hypoglycemia, or may present a lesion with high have visible ischemic changes within the first few hours T2 signal (shine-through phenomenon), and is negaof stroke [40–44]. Training in identification of early ischtive in up to 20% of patients with definite stroke [8]. emic changes on CT [43, 45, 46], and use of scoring sysAlthough areas abnormal on DWI often proceed to tems [42] improve detection of early ischemic changes. infarction, DWI can recover indicating that DWI does Early CT changes of ischemic stroke include denot show only permanently damaged tissue [58]. The crease in tissue X-ray attenuation, tissue swelling with degree of restricted water diffusion in the DWI lesion effacement of cerebrospinal fluid spaces, and arterial can be quantified by measuring the apparent diffusion hyperdensity which indicates presence of intraluminal thrombus with high specificity [47]. The visibility of intraluminal thrombi on CT depends on their hematocrit [48]. Swelling of ischemic brain tissue without hypoattenuation – present in 10–20% of acute stroke patients – is caused by compensatory vasodilation due to low perfusion pressure and is thus no “early infarct sign” [49]. CT detects changes in brain tissue water content of 1–2% equivalent to a decrease of 3–6 HU typically seen in acute ischemia, and is thus highly specific for the early identification of ischemic brain damage [41, 50, 51]. The presence a b of early signs of ischemia on CT Figures 3a and 3b. A 43-year-old woman with sudden onset of right-sided hemiparesis and aphashould not exclude patients from sia at 05:30 p.m. received full dose of intravenous recombinant tissue plasminogen activator thrombolysis within the first 3 h, within 1 h of stroke onset. CT at 08:41 p.m. still showed a hyperdense left MCA trunk (a) and a though patients with hypoattenutotal MCA territory infarction (b).


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coefficient (ADC). Tissue with only modestly reduced ADC values may be permanently damaged; there is as yet no reliable ADC threshold to differentiate dead from still viable tissue [59, 60]. Other MRI sequences (T2, FLAIR, T1) are inaccurate in the early detection of ischemic brain damage. MRI in patients with acute stroke should be reserved for young patients (who are more likely to have an unusual cause of stroke), patients with unusual presentations (e.g., suspected dissection, CADASIL), or in whom a stroke mimic (e.g., multiple sclerosis) is suspected which CT has not clarified. Some centers where MRI is more available than CT may choose to use MRI as first line routine investigation for acute stroke. If arterial dissection is considered (after trauma, stroke in the young even in the absence of trauma, in presence of Horner’s syndrome, or other specific symptoms), MRI of the neck is required in addition to brain MRI. Fatsuppressed T1-weighted sequences are sensitive to detect intramural hematoma. Perfusion imaging with CT or MRI and angiography may be used in selected patients with ischemic stroke to aid decision making concerning thrombolysis, although as yet there is no clear indication that patients with particular perfusion patterns are more or less likely to benefit from thrombolysis [61–64]. Selected patients with intracranial arterial occlusion may be candidates for intraarterial thrombolysis, although as yet there is no clear evidence of benefit for intraarterial over intravenous thrombolysis in patients with intracranial arterial thrombosis [65, 66]. Patients with combined obstructions of ICA and MCA have less chance of recovering with intravenous thrombolysis than patients with isolated MCA obstructions [34]. In patients with MCA trunk occlusions, the frequency of severe extracranial occlusive disease in the carotid distribution is very high with ICA occlusions in about 30% of patients and severe ipsilateral extracranial occlusive disease in 51% [67, 68]. The term “mismatch” describes a state, in which the volume of brain tissue with critical hypoperfusion – that is, brain tissue that does not recover without reperfusion – considerably exceeds the volume of infarcted tissue, tissue that does not recover even with reperfusion [69]. Mismatch can be detected with MR diffusion/ perfusion imaging with moderate reliability [70] and is not yet a proven strategy for improving the response to thrombolysis up to 9 h [71]. There is disagreement on how to best identify irreversible ischemic brain injury and to define critically impaired blood flow on MR and

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other modalities [61, 64, 72]. Quantification of MR perfusion is problematic on theoretical grounds [73]. Direct comparisons of several different perfusion parameters in the same patients show widely differing associations with clinical and radiologic outcomes [61, 74]. On CT perfusion maps, decrease in CBV (cerebral blood volume) is associated with subsequent tissue damage [62, 63], but like MR mismatch, the therapeutic impact of CT perfusion imaging is not yet determined. Findings indicate that although infarct expansion may occur in a high proportion of patients with mismatch, up to 50% of patients without mismatch may also have infarct growth (and so might benefit from tissue salvage) [64, 75]. The “imaging/clinical” mismatch, i.e., the mismatch between the extent of the lesion seen on DWI or CT and the extent of the lesion as expected from the severity of the neurologic deficit, has produced mixed results [76, 77]. Conflict of Interest Statement We certify that there is no actual or potential conflict of interest in relation to this article.

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Address for Correspondence Prof. Dr. Rüdiger von Kummer Department of Neuroradiology University Hospital of Dresden Fetscherstraße 74 01307 Dresden Germany Phone (+49/351) 458-2660, Fax -4370 e-mail: [email protected] Joanna M. Wardlaw Department of Clinical Neurosciences The University of Edinburgh Western General Hospital Crewe Rd Edinburgh, EH4 2XU UK Phone (+44/131) 5373110, Fax -3325150 e-mail: [email protected]
