Published online before print February 13, 2003, doi: 10.1161/01.STR.0000058161.89420.F4
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(Stroke. 2003;34:589.)
© 2003 American Heart Association, Inc.
Letters to the Editor |
Re: Stages and Thresholds of Hemodynamic Failure
Mallinckrodt Institute of Radiology and the Department of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
To the Editor:
We appreciate the opportunity to address several of the comments made by Nemoto and his colleagues1 regarding our prior work.
First, and most importantly, we would like to emphasize that measurements of oxygen extraction fraction (OEF) remain the most rigorously validated method for identifying stroke risk in patients with carotid occlusion.2 We must disagree with statements by Nemoto et al that OEF is not predictive of stroke risk. This conclusion is not valid, as it is based on erroneous interpretation of our data.
Increased OEF is predictive of stroke risk. The St. Louis Carotid Occlusion Study (STLCOS) was a blinded, prospective study of cerebral hemodynamics and stroke risk in patients with complete occlusion of a carotid artery.3 In this study, we prospectively set as a threshold the outer limits of the range of left-to-right hemispheric OEF ratios observed in a group of 18 neurologically normal control subjects. This threshold was established prior to the examination of the PET and outcome data for the 81 patients with symptomatic carotid occlusion. Eleven of the 13 patients with ipsilateral strokes occurring during the follow-up period had increased OEF, as defined by this threshold. Increased OEF was found to be both a powerful and independent predictor of subsequent stroke by Kaplan-Meier and multivariate analyses.3 Our findings were corroborated by a second study by Yamauchi et al.4
It is important to recognize that OEF has been shown to be predictive of stroke as a continuous variable, using either absolute values or hemispheric ratios.5 Nemoto et al are critical of the OEF threshold we used for absolute OEF in our recent article published in Brain.6 They also note that high OEF, as defined as the upper limit of the 95% reference range, did not identify all patients with subsequent stroke. This is true if this highly specific but insensitive threshold is used. This does not allow the conclusion that OEF does not predict stroke risk, however. Once the original hypothesis that OEF is an independent risk factor for stroke has been proven prospectively, the choice of any particular threshold is arbitrary and depends on the desired sensitivity and specificity for the test.
In the study in Brain, we reported that patients with increased OEF and increased CBV had a greater incidence of stroke than those with increased OEF and normal or reduced CBV.6 We did not find that increased OEF and normal CBV was not predictive of an increased risk of stroke.
The study in Brain was clearly identified as a retrospective review, as is true for all our publications since the initial publication of the prospective STLCOS data in 1998. The first sentence of the methods section in this article states, "The material for this analysis was drawn from a retrospective review of clinical and hemodynamic data ... from the STLCOS." It was not presented as a prospective study, as they state.
Second, Nemoto and colleagues propose the existence of a chronic, stable third stage of hemodynamic impairment beyond maximal autoregulatory vasodilation and increased oxygen extraction. This interesting new theory is not supported by any data. They do not provide any PET data demonstrating a progression from stage II to stage III, nor do they provide any outcome data to show that patients in stage III are at a high risk for stroke. Thus, this construct remains highly speculative. In the original schematic of Powers to which they refer, this region after maximal OEF elevation refers to acute stroke where OEF remains highly elevated for hours while CMRO2 gradually goes to zero.7
Finally, the relationship between vasodilatory capacity and stroke risk is variable. Well-designed, prospective studies of stroke risk have reported both positive and negative predictive value for tests of vasodilatory capacity.2,11,12
We agree that there are many questions to be answered regarding chronic regional hemodynamic impairment in humans and that more research needs to be done. The physiological relationships of oxygen extraction fraction, cerebral blood volume, and vasodilatory capacity are complicated and as yet poorly defined.8–10
References
1. Nemoto EM, Yonas H, Chang Y. Stages and thresholds of hemodynamic failure. Stroke. 2003; 34: 2–3. Letter.
2. Derdeyn CP, Grubb RL Jr, Powers WJ. Cerebral hemodynamic impairment: methods of measurement and association with stroke risk. Neurology. 1999; 53: 251–259.
3. Grubb RL Jr, Derdeyn CP, Fritsch SM, et al. The importance of hemodynamic factors in the prognosis of symptomatic carotid occlusion. JAMA. 1998; 280: 1055–1060.
4. Yamauchi H, Fukuyama H, Nagahama Y, et al. Significance of increased oxygen extraction fraction in five-year prognosis of major cerebral arterial occlusive disease. J Nucl Med. 1999; 40: 1992–1998.
5. Derdeyn CP, Videen TO, Grubb RL Jr, Powers WJ. Comparison of PET oxygen extraction fraction methods for the prediction of stroke risk. J Nucl Med. 2001; 42: 1195–1197.
6. Derdeyn CP, Videen TO, Yundt KD, et al. Variability of cerebral blood volume and oxygen extraction: stages of haemodynamic impairment revisited. Brain. 2002; 125: 595–607.
7. Powers WJ. Cerebral hemodynamics in ischemic cerebrovascular disease. Ann Neurol. 1991; 29: 231–240.[CrossRef][Medline] [Order article via Infotrieve]
8. Herold S, Brown MM, Frackowiak RSJ, Mansfield AO, Thomas DJ, Marshall J. Assessment of cerebral haemodynamic reserve: correlation between PET and CO2 reactivity measured by the intravenous 133 xenon injection technique. J Neurol Neurosurg Psychiatry. 1988; 51: 1045–1050.
9. Hirano T, Minematsu K, Hasegawa Y, Tanaka Y, Hayashida K, Yamaguchi T. Acetazolamide reactivity on I-IMP single photon emission computed tomography in patients with major cerebral artery occlusive disease: correlation with positron emission tomography parameters. J Cereb Blood Flow Metab. 1994; 14: 763–770.[Medline] [Order article via Infotrieve]
10. Sugimori H, Ibayashi S, Fujii K, Sadoshima S, Kuwabara Y, Fujishima M. Can transcranial Doppler really detect reduced cerebral perfusion states? Stroke. 1995; 26: 2053–2060.
11. Yokota C, Hasegawa Y, Minematsu K, Yamaguchi T. Effect of acetazolamide reactivity and long-term outcome in patients with major cerebral artery occlusive disease. Stroke. 1998; 29: 640–644.
12. Vernieri F, Pasqualetti P, Passarelli F, Rossini PM, Silvestrini M. Outcome of carotid artery occlusion is predicted by cerebrovascular reactivity. Stroke. 1999; 30: 593–598.
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