Focal Hypoperfusion in Acute Ischemic Stroke Perfusion CT: Clinical and Radiologic Predictors and Accuracy for Infarct Prediction.

BACKGROUND AND PURPOSE: Perfusion CT may improve the diagnostic performance of noncontrast CT in acute ischemic stroke. We assessed predictors of focal hypoperfusion in acute ischemic stroke and perfusion CT performance in predicting infarction on follow-up imaging. MATERIALS AND METHODS: Patients from the Acute STroke Registry and Analysis of Lausanne data base with acute ischemic stroke and perfusion CT were included. Clinical and radiologic data were collected. We identified predictors of focal hypoperfusion using multivariate analyses. RESULTS: From the 2216 patients with perfusion CT, 38.2% had an acute ischemic lesion on NCCT and 73.3% had focal hypoperfusion on perfusion CT. After we analyzed 104 covariates, high-admission NIHSS, visual field defect, aphasia, hemineglect, sensory deficits, and impaired consciousness were positively associated with focal hypoperfusion. Negative associations were pure posterior circulation, lacunar strokes, and anticoagulation. After integrating radiologic variables into the multivariate analyses, we found that visual field defect, sensory deficits, hemineglect, early ischemic changes on NCCT, anterior circulation, cardioembolic etiology, and arterial occlusion were positively associated with focal hypoperfusion, whereas increasing onset-to-CT delay, chronic vascular lesions, and lacunar etiology showed negative association. Sensitivity, specificity, and positive and negative predictive values of focal hypoperfusion on perfusion CT for infarct detection on follow-up MR imaging were 66.5%, 79.4%, 96.2%, and 22.8%, respectively, with an overall accuracy of 76.8%. CONCLUSIONS: Compared with NCCT, perfusion CT doubles the sensitivity in detecting acute ischemic stroke. Focal hypoperfusion is independently predicted by stroke severity, cortical clinical deficits, nonlacunar supratentorial strokes, and shorter onset-to-imaging delays. A high proportion of patients with focal hypoperfusion developed infarction on subsequent imaging, as did some patients without focal hypoperfusion, indicating the complementarity of perfusion CT and MR imaging in acute ischemic stroke.

An uncommon complication of Listeria monocytogenes infection: Polyradiculoneuritis following Listeria meningoencephalitis.

Listeria monocytogenes, primarily a foodborne pathogen, is commonly responsible for disorders affecting the central nervous system and cranial nerves. We hereby present the first case to our knowledge of listeriosis linked to a peripheral neurological disorder causing acute upper limb weakness.

Added value of multimodal computed tomography imaging: analysis of 1994 acute ischaemic strokes.

BACKGROUND AND PURPOSE: Multimodal computed tomography (CT) based imaging (MCTI) is widely used in acute ischaemic stroke. It was postulated that the use of MCTI is associated with improved patient outcome without causing harm. METHODS: All patients with an acute ischaemic stroke and CT-based imaging within 24 h from the ASTRAL (Acute Stroke Registry and Analysis of Lausanne) registry were included. Preceding demographic, clinical, biological, radiological and follow-up data were collected. Significant predictors of MCTI use were identified retrospectively to go on to fit a multivariable analysis. Then, patients undergoing additional CT angiography (CTA) or CTA and perfusion CT (CTP) were compared with non-contrast CT only patients with regard to 3-month favourable outcome (modified Rankin Scale score ≤2), 12-month mortality, stroke mechanism, short-term renal failure, use of ancillary diagnostic tests, duration of hospitalization and 12-month stroke recurrence. RESULTS: Of the 1994 included patients, 273 had only non-contrast CT, 411 had both non-contrast CT and CTA and 1310 had all three examinations. Factors independently associated with MCTI were younger age, low pre-stroke modified Rankin Scale score, low creatinine value, known stroke onset, anterior circulation stroke, anticoagulation or antihypertensive therapy (CTA only) and higher National Institutes of Health Stroke Scale scores (CTP only). After adjustment, MCTI was associated with a 50% reduction of 12-month mortality and a lower likelihood of unknown stroke mechanism. No association was found between MCTI and 3-month outcome, contrast-induced nephropathy, hospitalization duration, number of ancillary diagnostic tests or with stroke recurrence. CONCLUSION: Our study shows an association of MCTI use with lower adjusted 12-month mortality, better identification of the stroke mechanism and no signs of harm.

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. METHODS: In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m2 ) from underweight (<18.5 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (≥30 kg/m2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. RESULTS: Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. CONCLUSION: In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH.

Severe stroke: patient profile and predictors of favorable outcome.

BACKGROUND: Severe stroke carries high rates of mortality and morbidity. The aims of this study were to determine the characteristics of patients who initially presented with severe ischemic stroke, and to identify acute and subacute predictors of favorable clinical outcome in these patients. METHODS: An observational cohort study, Acute Stroke Registry and Analysis of Lausanne (ASTRAL), was analyzed, and all patients presenting with severe stroke - defined as a National Institute of Health Stroke Scale score of ≥ 20 on admission - were compared with all other patients. In a multivariate analysis, associations with demographic, clinical, pathophysiologic, metabolic and neuroimaging factors were determined. Furthermore, we analyzed predictors of favorable outcome (modified Rankin scale score of ≤ 3 at 3 months) in the subgroup of severe stroke patients. RESULTS: Of 1915 consecutive patients, 243 (12.7%) presented with severe stroke. This was significantly associated with cardio-embolic stroke mechanism (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.19-2.54), unknown stroke onset (OR 2.35, 95% CI 1.14-4.83), more neuroimaging signs of early ischemia (mostly computed tomography; OR 2.65, 95% CI 1.79-3.92), arterial occlusions on acute imaging (OR 27.01, 95% CI 11.5-62.9), fewer chronic radiologic infarcts (OR 0.43, 95% CI 0.26-0.72), lower hemoglobin concentration (OR 0.97, 95% CI 0.96-0.99), and higher white cell count (OR 1.05, 95% CI 1.00-1.11). In the 68 (28%) patients with favorable outcomes despite presenting with severe stroke, this was predicted by lower age (OR 0.94, 95% CI 0.92-0.97), preceding cerebrovascular events (OR 3.00, 95% CI 1.01-8.97), hypolipemic pretreatment (OR 3.82, 95% CI 1.34-10.90), lower acute temperature (OR 0.43, 95% CI 0.23-0.78), lower subacute glucose concentration (OR 0.74, 95% CI 0.56-0.97), and spontaneous or treatment-induced recanalization (OR 4.51, 95% CI 1.96-10.41). CONCLUSIONS: Severe stroke presentation is predicted by multiple clinical, radiologic and metabolic variables, several of which are modifiable. Predictors in the 28% of patients with favorable outcome despite presenting with severe stroke include hypolipemic pretreatment, lower acute temperature, lower glucose levels at 24 h, and arterial recanalization.

IL-2 mRNA levels and degradation rates change with mode of stimulation and phorbol ester treatment of lymphocytes.

Transient expression of interleukin 2 (IL-2) in activated T lymphocytes may be due to transcriptional and post-transcriptional regulation. As incubation of lymphocytes with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) prior to mitogenic stimulation results in decreased levels of IL-2 mRNA, we asked if IL-2 mRNA stability was affected. We found that in TPA-treated cells, IL-2 mRNA was degraded more rapidly than in untreated ones whether the mitogenic stimulus was Concanavalin A (Con A), Con A plus TPA, or TPA plus ionomycin. The degradation was blocked if the TPA pre-incubation included cycloheximide. In contrast, when TPA was included as a co-mitogen, i.e. added at the same time as the mitogen, the IL-2 mRNA levels and stability significantly increased. Compared to the levels found in Con A stimulated cells, TPA plus Con A increased IL-2 mRNA levels by as much as 20-fold and the half-life by 5-fold. TPA plus ionomycin increased the message levels at least 100-fold and half-life by nearly 10-fold. These effects on IL-2 mRNA were not general because IL-2 receptor mRNA stability was not changed even though it also is transiently expressed during the course of lymphocyte activation.

Evidence for ecto-protein kinase activity that phosphorylates Kemptide in a cyclic AMP-dependent mode.

The heptapeptide Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide) is a synthetic construct of a substrate for cAMP-dependent protein kinase (PK). In this work we show that Kemptide has all the properties of a cytophilic substrate, i.e. it is a molecule preserving cell membrane intactness when added to cultured cells. Kemptide thus satisfies the prerequisites for employment in assays for cell surface-located ecto-PK activity. Different types of intact cells catalyze the phosphorylation of Kemptide in the presence of extracellular ATP and cAMP with Km values of 3-4 microM for Kemptide. Kemptide phosphorylation was influenced by PKI, the inhibitory protein specific for cAMP-PK. The results of comparative experiments with intact cells and with cell extracts demonstrate the ectoenzyme nature of this cAMP-PK. Further, the possibility was ruled out of a transfer of enzyme activity from damaged cells to the surface of intact cells. The anchorage of the surface cAMP-PK activity to the plasma membrane appears to be relatively stable since (i) cell supernatants, obtained after preincubation of intact cells with cAMP or Kemptide, did not show Kemptide phosphorylation, and (ii) the cAMP-dependent PK activity remained with cells even after five consecutive washes with cAMP or Kemptide. This is in contrast to the ecto-cAMP-independent phosvitin/casein type PK (Kübler, D., Pyerin, W., Burow, E., and Kinzel, V. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 4021-4025) which is released from intact cells through the addition of substrate. Data are presented which show that both ectokinase activities are exhibited independently. In conjunction with published evidence for an active export of cAMP from cells as well as for the appearance of extracellular ATP the demonstration of an ecto-cAMP-PK further supports the potential of PK for intercellular regulation. The potential of ecto-cAMP-PK is demonstrated by its ability to phosphorylate biologically active forms of atrial natriuretic peptide, the atrial natriuretic peptide, which possesses the specific sequence for a cAMP-PK-catalyzed phosphorylation.