Diffusion-clinical mismatch

As described in the previous chapter on the ischemic penumbra, a patient with significant neurological deficit (NIHSS > 10), the finding of an ICA or proximal MCA occlusion and a small infarct core (<70-100 mL), very likelyhasavolumeofhypoperfused, symptom-producing tissue at risk that is at least 50% greater than the core volume. This concept was initially proposed as the diffusion-clinical mismatch [108, 109], and is based on the fact that the occlusion, core, and penumbra are not independent variables, but are related to each other by the collateral circulation. If one can identify two of the... 

Kane, 1., et al., Comparison of 10 different magnetic resonance perfusion imaging processing methods in acute ischemic stroke effect on lesion size, proportion of patients with diffusion/perfusion mismatch, clinical scores, and radiologic outcomes. Stroke, 2007. 38(12) p. 3158-64. 

The second prediction, that the diffusion-perfusion mismatch might be used to select acute stroke patients for thrombolytic therapy, is a compelling one that has generated a great deal of scientific debate and multiple clinical trials. Underlying this interest is the unfortunate fact that, although intravenous thrombolytic therapy is the most widely available treatment for acute stroke, only 1-7% of acute stroke patients receive it [62-65]. This is largely because the decision of whether or not to... 

Most of the studies that have addressed the hypothesis that the diffusion-perfusion mismatch can be used to select patients for thrombolysis have done so indirectly, by using the existence of the mismatch to widen, rather than replace the temporal window for treatment. The traditional 3-h window is based on several early clinical trials, in which thrombolysis was effective when administered to patients who were last seen without symptoms less than 3 h before treatment [69], but did not improve in outcomes when admiifistered after up to 5 [70] or 6 [71, 72] hours after onset. These studies did not use DWI or PWI, requiring only a noncontrast head CT examination to exclude the possibility of hemorrhage before thrombolysis could be initiated. A subsequent trial, which also did not incorporate DWI or PWI, found that thrombolysis could be effective up to 4.5 h, and this result has been used to widen the therapeutic window to 4.5 h at some centers [73]. 

Of great relevance to the potential use of multimodal MRI in extending the time window for thrombolysis have been the observations that perfusion-diffusion mismatch was present for up to 24 h after symptom onset (Table 3.2). Whilst the presence and volume of mismatch decreases over time, at least 50% of patients still have significant tissue at risk 24 h after stroke onset (Fig. 3.4). This correlates well with positron emission tomography studies that show penumbral tissue persists up to 48 h after symptom onset, and that spontaneous survival of this tissue results in clinical improvement (Markus et al. 2003 Read et al. 2000). There is mounting evidence that the time window for salvage of the penumbra is well beyond 3 h and multimodal MRI can identify such patients. 

It has been proposed that the phenomenon of DWI lesion reversal means that patients without perfusion-diffusion mismatch may still benefit from thrombolytic therapy (Kidwell et al. 2000). However, others consider more research is needed before adopting such an approach into clinical practice (Schellinger et al. 2003). We have not found that non-mismatch patients benefited from thrombolysis compared to historical controls (Parsons et al. 2002a). The ongoing Australasian Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) has been designed, in part, to answer the question of whether non-mismatch patients benefit from thrombolysis (Parsons et al. 2002a). 

Prosser J, Butcher K, Allport L, Parsons MW, Baird TA, MacGregor L, Tress BM, Davis SM (2004) Clinical-diffusion mismatch predicts the penumbra with high specificity. World stroke congress, Vancouver... 

Lansberg MG, Thijs VN, Hamilton S et al (2007) Evaluation of the clinical-diffusion and perfusion-diffusion mismatch models in DEFUSE. Stroke 38 1826-1830... 

Furthermore, patients selected with diffusion/perfusion MRI who are treated beyond 3 h do just as well as patients treated within 3 h. In a single center study, Ribo and colleagues [129] compared patients who arrived within 3 h of stroke onset and met the standard (including NCCT) criteria for the administration of tPA, with patients treated between 3 and 6 h after stroke onset who met the MRI criteria including a PWI/DWI mismatch of >50%. The outcomes for the two groups were similar with about 45% of patients having a good 3-month clinical outcome (mRS 0-3). Nearly 75% of the patients that arrived within the 3-6 h time limit met the diffusion/perfusion criteria. 

Staroselskaya lA, Chaves C, Silver B et al (2001) Relationship between magnetic resonance arterial patency and perfusion-diffusion mismatch in acute ischemic stroke and its potential clinical use. Arch Neurol 58 1069-1074... 

Janjua N, El-Gengaihy A, Pile-SpeUman Jet al (2009) Late endovascular revascularization in acute ischemic stroke based on clinical-diffusion mismatch. AJNR Am J Neuroradiol 30 1024-1027... 

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