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Objective mapping of irreversible tissue damage in the acute stage of ischaemic stroke would be useful for prognosis and in assessing the efficacy of therapeutic manoeuvres in impeding extension of infarction. From our database of 30 patients studied with 15O-PET within 5-18 h after onset of first-ever middle cerebral artery territory stroke, we extracted a subgroup of 19 survivors (age 74.6 +/- 8.5 years) in whom late CT coregistered with PET was available to determine final infarct topography. By means of a voxel-based analysis of the PET data, we determined putative thresholds for irreversible tissue damage as the lower limit of the 95% confidence interval calculated from all voxels within the ultimately non-infarcted brain parenchyma ipsilateral to the insult. The following values were found: 8.43 ml/100 ml/min, 0.87 ml/100 ml/min, 1.64 ml/100 ml, 0.27 and 2.21/min, for cerebral blood flow (CBF), oxygen consumption (CMRO2), blood volume (CBV), oxygen extraction fraction and the ratio CBF : CBV, respectively. Voxels below these thresholds occurred significantly more frequently in the final infarct region than in the non-infarcted parenchyma for CBF and CMRO2 (P = 0.016 and P = 0.0045, respectively, Wilcoxon test), but not for the other PET variables. Furthermore, with both CBF and CMRO2, the percentage of irreversible tissue damage voxels in the affected hemisphere relative to the opposite hemisphere was significantly positively correlated to both the volume of final infarct and the neurological outcome at 2 months (all P < 0.005, Spearman ranked test). These findings validate our voxel-based CBF and CMRO2 thresholds for probabilistic mapping of irreversible tissue damage within the 5-18 h interval after stroke onset; however, whether they would be applicable to earlier intervals remains to be determined. Transfer of our procedure for determination of irreversible tissue damage thresholds to other imaging modalities such as single proton emission computed tomography and diffusion-weighted MRI should be straightforward.

The authors searched for mutations in the beta-amyloid precursor protein in a Spanish family with a hereditary syndrome of hemorrhagic stroke, dementia, leukoencephalopathy, and occipital calcifications. DNA from two affected members demonstrated the Iowa amyloid precursor protein mutation previously identified as a cause of severe amyloid angiopathy without hemorrhagic stroke. These data point to other genetic or environmental factors that may determine the occurrence of symptomatic hemorrhage in amyloid angiopathy.

We found no evidence for an influence of cCMRO2 on acute-stage neurological deficit or for a role of the unaffected hemisphere in early recovery after acute MCA ischemic stroke. The decline in unaffected-hemisphere metabolism from the acute to the subacute stage in the face of overall clinical recovery appears clinically irrelevant. The fact that the neocortical cCMRO2 at PET2 tended to be lower, and declined significantly from PET1 to PET2 in the mirror region in the subgroup of patients with large infarcts, suggests that this delayed effect represents transcallosal fiber degeneration.

Depicting the salvageable tissue is increasingly used in the clinical setting following stroke. As absolute cerebral blood flow (CBF) is difficult to measure using perfusion magnetic resonance or computed tomography and has limitations as a penumbral marker, time-based variables, particularly the mean transit time (MTT), are routinely used as surrogates. However, a direct validation of MTT as a predictor of the penumbra threshold using gold-standard positron emission tomography (PET) is lacking. Using 15 O-PET data sets obtained from two independent acute stroke samples (N = 7 and N = 30, respectively), we derived areas under the curve (AUCs), optimal thresholds (OTs), and 90%-specificity thresholds (90%-Ts) from receiver operating characteristic curves for absolute MTT, MTT delay, and MTT ratio to predict three penumbra thresholds ('classic': CBF < 20 mL/100 g per min; 'normalized': CBF ratio < 0.5; and 'stringent': both CBF < 20 mL/100 g per min and oxygen extraction fraction > 0.55). In sample 1, AUCs ranged from 0.79 to 0.92, indicating good validity; OTs ranged from 7.8 to 8.3 seconds, 2.8 to 4.7 seconds, and 151% to 267% for absolute MTT, MTT delay, and MTT ratio, respectively, while as expected, 90%-Ts were longer. There was no significant difference between sample 1 and sample 2 for any of the above measurements, save for a single MTT parameter with a single penumbra threshold. These consistent findings from gold-standard PET obtained in two independent cohorts document that MTT is a very good surrogate to CBF for depicting the penumbra threshold.

These findings were consistent with the diagnosis of a paraneoplastic neurological syndrome, although both optic neuritis and remission of the cerebellar syndrome are uncommon patterns of paraneoplastic syndromes. CV2 antigen expression by the oligodendrocytes of the cerebellum, brainstem, spinal cord, and optic chiasm correlated with the clinical syndrome observed in our patient. However, the precise pathophysiological role of anti-CV2 antibodies is still unknown.

Background and Purpose: Combined perfusion and oxygen metabolism PET imaging is highly predictive of spontaneous outcome after middle cerebral artery (MCA) stroke, independent of clinical scores, but whether the assessment of perfusion alone by SPECT provides similar information remains unclear. We have assessed the prognostic value of ^99mTc-HMPAO-SPECT at the acute stage of stroke. Methods: Twenty-seven first-ever nonhemorrhagic MCA territory stroke patients were prospectively studied 4–20 h (mean: 12 h) after onset with ^99mTc-HMPAO-SPECT. None was part of a therapeutic trial or received thrombolysis. Neurological deficits were quantified at admission and 2 months later with Orgogozo’s MCA scale. SPECT images were visually classified by 3 independent observers into one of three patterns, as follows: pattern I = marked and extensive tracer hypofixation; pattern II = moderate and/or focal hypofixation with or without combined hyperfixation, and pattern III = normal or increased uptake without hypofixation. In addition to this visual analysis, we also calculated a voxel-based ‘hypoperfusion score’, an index of severity × extent of hypofixation according to Mountz’s method. Results: There was a good intra- and interobserver agreement. After consensus, 9, 14 and 4 patients were classified in patterns I, II and III, respectively. These patterns had a significant predictive value for raw outcome but not for percentage recovery (p = 0.008 and p = 0.127, respectively). Thus, all patients in pattern III had a good outcome, while most (but not all) patients in pattern I had a poor or intermediate outcome; pattern II patients were more evenly distributed among outcomes. Hypoperfusion scores were highly significantly positively correlated with both 2-month outcomes and percentage recoveries, even after controlling the predictive value of day 0 MCA scores by partial correlations. Comments: We found that SPECT had a significant added predictive value even when compared to admission neurological scores. Although less accurate than PET, ^99mTc-HMPAO-SPECT may help to predict spontaneous individual neurological evolution, especially whenever perfusion images are normal or show an increased tracer uptake without associated hypofixation.