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Using PET to identify carotid occlusion patients at high risk of subsequent stroke: further insights
  1. J-C Baron
  1. Department of Clinical Neurosciences and Stroke Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
  1. Correspondence to:
 J-C Baron
 Department of Clinical Neurosciences and Stroke Unit, University of Cambridge, Addenbrooke’s Hospital, Box 83, Cambridge, CB2 2QQ, UK

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Identifying carotid occlusion patients at risk of stroke

Although atherothrombotic occlusion of the internal carotid artery (ICA) can cause a devastating stroke, in many instances it is a benign event, causing only transient ischaemic attacks (TIAs), a minor stroke, or even no symptom at all. Despite optimal medical treatment, however, the subsequent risk of stroke in patients with symptomatic ICA occlusion is around 7% per year, with 6% ipsilateral. It would be important to be able to identify patients at high risk of subsequent stroke to implement appropriate prevention. Studies performed over the last two decades have provided strong evidence that haemodynamic factors play a major role in such risk. The association of focally decreased cerebral blood flow (CBF) and increased oxygen extraction fraction (OEF)—coined “misery perfusion”—was first described in a patient with medically intractable TIAs distal to a previously documented ICA occlusion with poor collateralisation.1 This abnormal physiology pointed to reduction in perfusion pressure beyond the lower limit of autoregulation, so quite logically an extracranial-intracranial bypass was performed, after which both the TIAs and the misery perfusion resolved.1 Prospective studies have since documented that in patients with symptomatic ICA occlusion the presence of misery perfusion (or severely impaired vasodilatory reserve as a surrogate) considerably increases the risk of subsequent ipsilateral stroke, with an odds ratio of 7 to 8.2–5 This in turn led to challenge of the negative results of the international EC-IC bypass study, of which haemodynamic assessment was not part. Accordingly, two trials this time focusing only on patients with documented misery perfusion or inadequate vasodilation reserve are currently underway in the US and Japan. However, whether knowledge of the pattern of collaterals predicts the presence of misery perfusion and therefore avoids complicated physiological investigations would be important to know. In view of the contradictory findings from earlier studies, Yamauchi et al6 have revisited the issue and their results are published in this issue (pp 1697–701).

Their hypothesis was that cortical metabolic depression secondary to diaschisis or to selective neuronal damage might confound the occurrence of high OEF. By reducing synaptic activity, cortical diaschisis—a frequent occurrence in striato-capsular infarction, probably secondary to disruption of the thalamo-cortical fibres,7—might reset the perfusion-metabolism imbalance and thus “mask” misery perfusion (fig 1). Selective neuronal damage secondary to episodes of ischaemia is another putative cause of cortical metabolic depression.8 Supporting their hypothesis, Yamauchi et al found that the presence of ophthalmic or leptomeningeal collateralisation (assessed by conventional four vessel angiography) predicted the occurrence of misery perfusion, but only in the absence of striatocapsular infarction.

Figure 1

 Idealised graph illustrating the expected increase in oxygen extraction fraction (OEF) from its physiological value of around 40% in the face of a primary reduction in cerebral blood flow (CBF) below its physiological value of around 50 ml.100 g−1 min−1, and the resetting of this relationship towards normal levels of OEF in the presence of primary metabolic depression such as induced by superimposed diaschisis.

The clinical implications from this work are potentially important—the presence of ophthalmic or leptomeningeal collaterals in a patient with no striatocapsular infarct accurately predicts increased OEF, and in turn a high risk of subsequent ipsilateral stroke. It remains to be seen if some patients without misery perfusion as a result of subcortical infarct are still at a high risk of subsequent ipsilateral stroke, and whether other indicators of impaired haemodynamic reserve would identify them. Also, whether the clinical presentation—especially continuing haemodynamic type TIAs—helps in identifying ICA occlusion patients at high risk of stroke would be worth investigating.

This study has pathophysiological implications in cerebrovascular disease beyond chronic ICA occlusion. For instance, does diaschisis afford neuroprotection to the penumbral cortex in the acute stage of stroke in the presence of an early striato-capsular core?

Identifying carotid occlusion patients at risk of stroke

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