Lucas Restrepo

Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging of the Brain Before and After Coronary Artery Bypass Grafting Surgery

Background and Purpose— Coronary artery bypass grafting (CABG) is a frequently performed surgical procedure that can be associated with neurological complications. Some studies have demonstrated that new focal brain lesions, detected by MRI, can develop after CABG. Furthermore, it has been suggested that the presence of such new lesions is associated with a decline in neurocognitive test scores. Advanced MRI techniques, including diffusion- (DWI) and perfusion-weighted imaging (PWI), offer important diagnostic advantages over conventional imaging in the assessment of patients undergoing CABG. We sought to determine whether focal PWI and DWI abnormalities could occur after CABG, particularly in patients without any measurable neurological deterioration. Methods— Thirteen patients prospectively underwent MRI with DWI and PWI before and after CABG. A battery of neurocognitive tests was administered before and after surgery. Demographic, clinical, and radiographic characteristics of the patients were collected and compared. Results— Four patients developed new DWI defects after CABG. The lesions were small, rounded, and multiple (3 of 4 patients). One of these patients was diagnosed with stroke on clinical grounds. The patients with new lesions had a larger neurocognitive decline than their counterparts with stable MRI. Other clinical characteristics of patients with new DWI lesions, including stroke risk factors, were similar to those of patients without MRI changes. No focal perfusion abnormalities were observed on preoperative or postoperative scans. Conclusions— Postoperative DWI abnormalities can occur after CABG, even in patients without overt neurological defects. The PWI scans remained unchanged. Larger prospective studies are required to determine whether the new lesions are clearly associated with neurocognitive decline or with specific perioperative stroke risk factors.

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis

Background: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. Methods: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. Results: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. Conclusions: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

Variability in Subcortical Aphasia Is Due to Variable Sites of Cortical Hypoperfusion.

A variety of fluent and nonfluent aphasias have been reported after left basal ganglia stroke. It has been speculated that this heterogeneity may reflect variations in cortical hypoperfusion resulting from large vessel stenosis. To test this hypothesis, a consecutive series of 24 patients with left caudate infarct identified with diffusion-weighted imaging underwent language testing and perfusion-weighted imaging < 24h from onset of symptoms. Specific regions in perisylvian cortex were rated for the percentage of the region that was hypoperfused. Aphasia type was determined on the basis of speech fluency, comprehension, and repetition performance on the language tests. Association between aphasia type/language impairment and regions of hypoperfusion were identified with Fishers exact tests. Results demonstrated that in patients with acute left caudate infarct, the presence and type of aphasia reflected regions of hypoperfusion, and generally followed predictions based on chronic lesion studies, regarding anatomical lesions associated with classic aphasia types.

Application of immunosignatures to the assessment of Alzheimer's disease.

Accurate assessment of Alzheimers disease (AD), both presymptomatically and at different disease stages, will become increasingly important with the expanding elderly population. There are a number of indications that the immune system is engaged in AD. Here we explore the ability of an antibody‐profiling technology to characterize AD and screen for peptides that may be used for a simple diagnostic test.

Safety of Induced Hypertension Therapy in Patients With Acute Ischemic Stroke

IntroductionThe management of blood pressure in acute stroke is controversial. Small pilot studies have suggested that blood pressure augmentation improves short-term neurological function, but the rate of adverse events with induced hypertension (IH) therapy is unknown.Methods and ResultsWe reviewed 100 consecutive patients who underwent perfusion magnetic resonance imaging for acute ischemic stroke. IH therapy was employed in 46 patients and standard therapy (ST) in 54. The two groups had similar baseline characteristics, but more patients in the IH group had significant large-artery stenoses. The IH group achieved significantly higher mean arterial pressure (MAP) than the ST group within 3 days of initiation of therapy with a variety of vasopressor agents. Only 35% of patients in the IH group actually achieved the target MAP augmentation of 10–20% above baseline, however. All patients survived to discharge. Four patients experienced major adverse events in each group. Two patients in the IH group experienced intracerebral hemorrhage compared to none in the ST group. Two patients in the ST group experienced myocardial ischemia, compared to none in the IH group. The National Institutes of Health Stroke Scale during the hospitalization and place of discharge were similar in both groups. Patients in the IH group were more likely to be admitted to the intensive care unit and had a longer hospital stay by nearly 4 days compared to the ST group.ConclusionThese data demonstrate the relative safety of IH therapy in acute stroke patients. Given the greater use of resources, however, the role of IH in improving clinical outcomes requires a prospective, randomized trial.

A Model to Prevent Fibrinolysis in Patients with Stroke Mimics

BACKGROUND Many patients with stroke-mimicking conditions receive treatment with intravenous fibrinolysis (IVF), a treatment associated with potentially serious complications. We sought to determine if any clinical or radiographic characteristics can help predict stroke mimics among IVF candidates. METHODS This retrospective study was carried out at a single institution. Patients treated with intravenous recombinant tissue plasminogen activator (rt-PA; n = 193) were divided into 3 categories: acute ischemic stroke (n = 142), aborted stroke (n = 21), and stroke mimics (n = 30). Analysis of variance and the chi-square test were used to assess differences, while logistic regression models were computed to predict groups. RESULTS Mimics treated with rt-PA did not experience complications (intracranial bleeding, systemic hemorrhage, or angioedema), and had better neurologic and functional outcomes than stroke patients (P < .05). Several variables helped differentiate strokes from mimics, including atherosclerosis on computed tomographic angiography (odds ratio [OR] 23.6; 95% confidence interval [CI] 8.4-66.2), atrial fibrillation (OR 11.4; 95% CI 1.5-86.3), age >50 years (OR 7.2; 95% CI 2.8-18.5), and focal weakness (OR 4.15; 95% CI 1.75-9.8). Other variables decreased chances of stroke: migraine history (OR 0.05; 95% CI 0.01-0.4), epilepsy (OR 0.13; 95% CI 0.02-0.8), paresthesia (OR 0.1; 95% CI 0.04-0.3), and precordialgia (OR 0.045; 95% CI 0.002-0.9). A regression model using focal weakness, computed tomographic angiography findings, and precordialgia had a 90.2% predictive accuracy. CONCLUSIONS IVF has low complication rates in stroke mimics. Certain clinical characteristics appear predictive of stroke mimics, particularly normal computed tomographic angiography. If confirmed, this may help prevent giving IVF to patients without stroke.

Simultaneous ring voice-over-Internet phone system enables rapid physician elicitation of explicit informed consent in prehospital stroke treatment trials.

Background: Cellular phone conversations between on-scene patients or their legally authorized representatives (LARs) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials. Methods: The NIH Field Administration of Stroke Therapy – Magnesium (FAST-MAG) Trial implemented a voice-over-internet protocol (VOIP) simultaneous ring system (multiple investigator cell phones called simultaneously and first responder connected to call) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial. For 1 month, the number, origin, duration, and yield of enrolling line calls were monitored prospectively. Results: Six investigators were connected to 106 enrolling line calls, with no identified unanswered calls. Thirty-five percent of new patient calls yielded an enrollment. The most common reasons for non-enrollment were last known well >2 h (n = 7) and uncon sentable patient without LAR available (n = 7). No non-enrollments were directly attributable to the VOIP system. In enrollments, consent was provided by the patient in 67% and a LAR in 33%. The duration of enrollment calls (mean ± SD: 8.4 ± 2.5 min, range 6–14) was longer than non-enrollment calls (5.5 ± 3.5, range 2–13; p < 0.001). The median interval from last known well to study agent start was 46 min, and 70% were enrolled within 60 min of onset. Conclusions: The simultaneous ring system was reliable and effective, permitting enrollment of a substantial number of patients within the first hour after stroke onset. VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials.

Feasibility of an early Alzheimer's disease immunosignature diagnostic test

A practical diagnostic test is needed for early Alzheimers disease (AD) detection. Immunosignaturing, a technology that employs antibody binding to a random-sequence peptide microarray, generates profiles that distinguish transgenic mice engineered with familial AD mutations (APPswe/PSEN1-dE9) from non-transgenic littermates. It can also detect an AD-like signature in humans. Here, we assess the changes in the immunosignature at different time points of the disease in mice and humans. We also evaluate the accuracy of the late-stage signature as a test to discriminate between young mice with familial AD mutations from non-transgenic littermates. Plasma samples from AD patients were assayed 3-12 months apart, while APPswe/PSEN1-dE9 and non-transgenic controls supplied plasma at monthly intervals until they reached 15 months of age. Microarrays with 10,000 random-sequence peptides were used to compare antibody binding patterns. These patterns gradually changed over the life-span of mice. Strong, characteristic signatures were observed in transgenic mice at early, mid and late stages, but these profiles had minimal overlap. The signature of young transgenic mice had an error rate of 18% at classifying plasma samples from late-stage transgenic mice. Conversely, the late-stage transgenic mice signature discriminated between young transgenic mice and littermates with an error rate of 21%. Less distinctive profiles were recognizable throughout the transgenic mice lifespan, being detectable as early as 2 months. The human signature had minimal change on short-term follow-up. Our results call for a reappraisal of the way incipient AD is studied, as biomarkers seen in late-stages of the disease may not be relevant in earlier stages.

Impact of Hyperlipidemia and Statins on Ischemic Stroke Outcomes after Intra-Arterial Fibrinolysis and Percutaneous Mechanical Embolectomy

Background: Endovascular recanalization therapies are an increasingly employed treatment strategy in acute cerebral ischemia. The determinants of the final clinical outcome after endovascular treatment have been understudied. We investigated the effects of hyperlipidemia and statins on acute ischemic stroke outcomes after endovascular procedures. Methods: An inquiry of a prospectively maintained stroke registry was conducted. Endovascular procedures were performed using recombinant tissue plasminogen activator, prourokinase or the Merci device within 12 hours after symptom onset. The analyzed outcomes were revascularization, hemorrhage and excellent functional outcome (Rankin score of 0–1 at 3 months). The analyses included χ2 and Wilcoxon rank sum, logistic regression (for multivariate analyses with binary outcomes) and linear regression (for continuous outcomes). Significance was set at p < 0.05. Results: We included 142 patients, 80% treated with intra-arterial fibrinolysis, 22% with percutaneous mechanical embolectomy and 27% treated with intravenous fibrinolysis prior to endovascular intervention. Age (OR = 0.956, 95% CI = 0.927–0.986, p = 0.0041), National Institutes of Health Stroke Scale (NIHSS) score on admission (OR = 0.881, 95% CI = 0.812–0.957, p = 0.0025) and history of hyperlipidemia (OR = 0.284, 95% CI = 0.08–0.99, p = 0.0478) were negatively associated with excellent functional outcome at 3 months. Every 50 mg/dl increment in the total cholesterol level resulted in 64% decrease in the odds of excellent functional outcome (OR = 0.36, 95% CI = 0.447–0.882, p = 0.0253). History of hyperlipidemia decreased the likelihood of neurological improvement (p = 0.0462) and was associated with a higher NIHSS score at 7 days or discharge. Statin use was related to an average 6.5-unit NIHSS decrease at discharge (p = 0.0168). Statins were not associated with increased frequency of recanalization or symptomatic intracerebral hemorrhage. Conclusions: History of hyperlipidemia may have a negative impact on the outcomes of acute ischemic stroke treated with intra-arterial fibrinolysis or percutaneous mechanical embolectomy. Statin use before and after these procedures may be related to better neurological outcomes. Larger prospective studies are needed to endorse these findings.

Patients with Diffusion‐Perfusion Mismatch on Magnetic Resonance Imaging 48 Hours or More After Stroke Symptom Onset: Clinical and Imaging Features

Background. Abnormalities in diffusion‐weighted (DWI) and perfusion‐weighted (PWI) magnetic resonance imaging (MRI) are thought to reflect the presence of brain tissue at risk for ischemic stroke. Many patients with acute ischemic stroke have a mismatch pattern in which the PWI volume is larger than the DWI lesion. This mismatch typically resolves over 24‐48 hours. Little is known about the presence of DWI‐PWI mismatch in later stages of stroke.