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Diffusion MRI in Patients With Transient Ischemic Attacks

BACKGROUND AND PURPOSE Diffusion MRI has established value in patients with ischemic stroke but has not been systematically investigated in patients with transient ischemic attack (TIA). METHODS Clinical, conventional MRI, and diffusion MRI data were collected on 42 consecutive patients with symptoms of cerebral TIA. TIA imaging data were compared with those from a contemporaneous group of 23 completed stroke patients. RESULTS Twenty of the 42 TIA patients (48%) demonstrated neuroanatomically relevant focal abnormalities on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) imaging. When present, DWI/ADC signal changes in TIA patients were less pronounced and smaller in volume than those in completed stroke patients. TIA symptom duration was significantly longer for DWI-positive than for DWI-negative patients, 7.3 versus 3.2 hours. Diffusion MRI information changed the suspected anatomic and vascular TIA localization and the suspected etiologic mechanism in over one third of patients with diffusion MRI abnormalities. Of the 20 TIA patients with identifiable lesions on diffusion MRI, 9 had follow-up imaging studies; of these, 4 did not show a relevant infarct on follow-up imaging. CONCLUSIONS Diffusion MRI demonstrates ischemic abnormalities in nearly half of clinically defined TIA patients. The percentage of patients with a DWI lesion increases with increasing total symptom duration. In nearly half, the diffusion MRI changes may be fully reversible, while in the remainder the diffusion MRI findings herald the development of a parenchymal infarct despite transient clinical symptoms. Finally, diffusion imaging results have significant clinical utility, frequently changing the presumed localization and etiologic mechanism.

Recommendations for Imaging of Acute Ischemic Stroke A Scientific Statement From the American Heart Association

Stroke is a common and serious disorder, with an incidence of ≈795 000 each year in the United States alone. Worldwide, stroke is a leading cause of death and disability. Recombinant tissue plasminogen activator (rtPA) was approved a decade ago for the treatment of acute ischemic stroke. The guidelines for its use include stroke onset within 3 hours of intravenous drug administration, preceded by a computed tomographic (CT) scan to exclude the presence of hemorrhage, which is a contraindication to the use of the drug. Although randomized, controlled studies in Europe and North America demonstrated the efficacy of this treatment, it also was associated with an incidence of intracranial hemorrhage of 6.4%,1,2⇓ which was shown on subsequent studies to be even greater if there was not strict adherence to the administration protocol.3 The goal of these controlled studies was to evaluate patient outcome. There was no attempt to determine the site, or even the actual presence, of a vascular occlusion, the degree of tissue injury, or the amount of tissue at risk for further injury that might be salvageable. More than a decade later, progress for treating acute ischemic stroke has been slow,4,5⇓ yet the goals for treating this common disease have expanded. First, there is the need to extend the therapeutic window from 3 to ≥6 hours. Even with the rapid communication and transportation in our societies today, very few patients present for treatment within 3 hours.6 Second, there is the desire to improve the efficacy of treatment. It had been shown even before the randomized, controlled studies that intravenous rtPA works better in small peripheral vessels than in the large vessels at the skull base.7 Third, there is a need to decrease the complication rate, especially if patients are to be …

Brain ferritin iron may influence age- and gender-related risks of neurodegeneration

BACKGROUND Brain iron promotes oxidative damage and protein oligomerization that result in highly prevalent age-related proteinopathies such as Alzheimers disease (AD), Parkinsons disease (PD), and Dementia with Lewy Bodies (DLB). Men are more likely to develop such diseases at earlier ages than women but brain iron levels increase with age in both genders. We hypothesized that brain iron may influence both the age- and gender-related risks of developing these diseases. METHODS The amount of iron in ferritin molecules (ferritin iron) was measured in vivo with MRI by utilizing the field dependent relaxation rate increase (FDRI) method. Ferritin iron was measured in four subcortical nuclei [caudate (C), putamen (P), globus pallidus (G), thalamus (T)], three white matter regions [frontal lobe (Fwm), genu and splenium of the corpus callosum (Gwm, Swm)] and hippocampus (Hipp) in 165 healthy adults aged 19-82. RESULTS There was a high correlation (r>0.99) between published post-mortem brain iron levels and FDRI. There were significant age-related changes in ferritin iron (increases in Hipp, C, P, G, and decreases in Fwm). Women had significantly lower ferritin iron than men in five regions (C, T, Fwm, Gwm, Swm). CONCLUSIONS This is the first demonstration of gender differences in brain ferritin iron levels. It is possible that brain iron accumulation is a risk factor that can be modified. MRI provides the opportunity to assess brain iron levels in vivo and may be useful in targeting individuals or groups for preventive therapeutic interventions.

Lifespan trajectory of myelin integrity and maximum motor speed.

OBJECTIVE Myelination of the human brain results in roughly quadratic trajectories of myelin content and integrity, reaching a maximum in mid-life and then declining in older age. This trajectory is most evident in vulnerable later myelinating association regions such as frontal lobes and may be the biological substrate for similar trajectories of cognitive processing speed. Speed of movement, such as maximal finger tapping speed (FTS), requires high-frequency action potential (AP) bursts and is associated with myelin integrity. We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity. METHODS A sensitive in vivo MRI biomarker of myelin integrity (calculated transverse relaxation rates (R(2))) of frontal lobe white matter (FLwm) was measured in a sample of very healthy males (N=72) between 23 and 80 years of age. To assess specificity, R(2) of a contrasting early-myelinating region (splenium of the corpus callosum) was also measured. RESULTS FLwm R(2) and FTS measures were significantly correlated (r=.45, p<.0001) with no association noted in the early-myelinating region (splenium). Both FLwm R(2) and FTS had significantly quadratic lifespan trajectories that were virtually indistinguishable and both reached a peak at 39 years of age and declined with an accelerating trajectory thereafter. CONCLUSIONS The results suggest that in this very healthy male sample, maximum motor speed requiring high-frequency AP burst may depend on brain myelin integrity. To the extent that the FLwm changes assessed by R(2) contribute to an age-related reduction in AP burst frequency, it is possible that other brain functions dependent on AP bursts may also be affected. Non-invasive measures of myelin integrity together with testing of basic measures of processing speed may aid in developing and targeting anti-aging treatments to mitigate age-related functional declines.

Early MRI and outcomes of untreated patients with mild or improving ischemic stroke

Objective: To determine the frequency of early neurologic deterioration with infarct expansion (ENDIE) and poor outcomes among ischemic stroke patients not treated with reperfusion therapies because of rapidly improving or mild symptoms (RIMS) and to study the predictive value of hyperacute MRI in these patients. Methods: We identified consecutive patients with symptoms of acute stroke undergoing multimodal MRI within 6 hours of onset without evidence of hemorrhage on imaging. Medical records were reviewed for evidence of early neurologic deterioration within 48 hours. All deteriorating patients had repeat MRI to ascertain causes of worsening. Poor outcome was defined as a discharge modified Rankin Scale (mRS) score of ≥3. Results: We identified 74 patients with stroke symptoms ≤6 hours from onset. Forty had RIMS, and 39 did not receive reperfusion therapies because of RIMS. Among these 39, 4 experienced ENDIE, and 8 were discharged with mRS score of ≥3. Eight of the 39 patients had large-vessel occlusions on MR angiography. Three of 8 patients with large-vessel occlusion as against only one of 31 patients without occlusion had ENDIE (odds ratio [OR] 18, 95% CI 1.6 to 209, p = 0.02). Four of 8 patients with large-vessel occlusion as against 4 of 31 patients without occlusion had a discharge mRS score of ≥3 (OR 7, 95% CI 1.2 to 38, p = 0.04). Conclusions: About 10% of patients eligible for acute reperfusion therapy excluded on the basis of mild or rapidly improving symptoms show early neurologic deterioration with infarct expansion within 48 hours, and about 20% show poor outcome at discharge. Persisting large-vessel occlusion substantially increases the risk of early worsening and poor functional outcome.

A Brief Prehospital Stroke Severity Scale Identifies Ischemic Stroke Patients Harboring Persisting Large Arterial Occlusions

Background and Purpose— The Los Angeles Motor Scale (LAMS) is a brief 3-item stroke severity assessment measure designed for prehospital and Emergency Department use. Methods— The LAMS and NIHSS were scored in under-12-hour acute anterior circulation ischemic stroke patients. Stroke severity ratings were correlated with cervicocerebral vascular occlusion on CTA, MRA, and catheter angiography. Receiver operating curves, c statistics, and likelihood ratios were used to evaluate the predictive value for vascular occlusion of stroke severity ratings. Results— Among 119 patients, mean age was 67 (±18), 45% were male. Time from onset to ED arrival was mean 190 minutes (range 10 to 660). Persisting large vessel occlusions (PLVOs) were present in 62% of patients. LAMS stroke severity scores were higher in patients harboring a vascular occlusion, median 5 (IQR 4 to 5) versus 2 (IQR 1 to 3). Similarly, NIHSS stroke severity scores were higher in PLVO patients, 19 (14 to 24) versus 5 (3 to 7). ROC curves demonstrated that the LAMS was highly effective in identifying patients with PLVOs, c statistic 0.854. At the optimal threshold of 4 or higher, LAMS scores showed sensitivity 0.81, specificity 0.89, and overall accuracy 0.85. LAMS performance was comparable to NIHSS performance (c statistic 0.933). The positive likelihood ratio associated with a LAMS score ≥4 was 7.36 and the negative likelihood ratio 0.21. Conclusions— Stroke severity assessed by the LAMS predicts presence of large artery anterior circulation occlusion with high sensitivity and specificity. The LAMS is a promising instrument for use by prehospital personnel to identify select stroke patients for direct transport to Comprehensive Stroke Centers capable of endovascular interventions.

Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury.

Objective:To determine whether persistent metabolic dysfunction in normal-appearing frontal lobe tissue is correlated with long-term tissue atrophy. Design:Prospective monitoring with retrospective data analysis. Setting:Single-center academic neurointensive care unit. Patients:Fifteen patients with moderate to severe traumatic brain injury (Glasgow Coma Scale score 3–12). Interventions:None. Measurements and Main Results:Hourly cerebral microdialysis was performed for the initial 96 hrs after trauma to determine extracellular levels of glucose, glutamate, glycerol, lactate, and pyruvate in normal appearing frontal lobes. Six months after injury, the anatomical outcome was assessed by measures of global and regional cerebral atrophy using volumetric brain magnetic resonance imaging. The lactate/pyruvate ratio was elevated >40 after traumatic brain injury in most patients, with a mean percent time of 32 ± 29% of hours monitored. At 6 months after traumatic brain injury, there was a mean frontal lobe atrophy of 12 ± 11% and global brain atrophy of 8.5 ± 4.5%. The percentage of time of elevated lactate/pyruvate ratio correlated with the extent of frontal lobe brain atrophy (r = −.56, p < 0.01), but not global brain atrophy (r = −.31, p = 0.20). The predictive effect of lactate/pyruvate ratio was independent of patient age, Glasgow Coma Scale score, and volume of frontal lobe contusion. Conclusion:Persistent metabolic crisis, as reflected by an elevated lactate/pyruvate ratio, in normal appearing posttraumatic frontal lobe, is predictive of the degree of tissue atrophy at 6 months.

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.

Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals

BACKGROUND Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers. METHODS Healthy subjects (n = 171) 14-93 years of age were examined with transverse relaxation rate (R(2)) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively). RESULTS Only R(2) reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R(2) < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R(2) and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor. CONCLUSIONS The R(2) and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.

Time-resolved contrast enhanced magnetic resonance angiography of the head and neck at 3.0 tesla: Initial results

Objectives:We sought to implement and evaluate a high-performance, extended field of view protocol for time-resolved contrast-enhanced magnetic resonance imaging (CEMRA) of the carotid circulation by using a dedicated neurovascular (NV) array coil. Materials and Methods:A total of 16 adult volunteers and 20 clinical patients with suspected cerebrovascular disease (15 male, 21 female, 25–82 years of age) were scanned with a fast 3D MRA sequence (TR/TE: 2.16/1 milliseconds, sampling BW: 1090 Hz/pixel), with echo-sharing and parallel acquisition. All studies were performed on a 3.0 T MR system using an 8-channel neurovascular array coil. After injection of 6 mL of gadodiamide at 3 mL/s, a coronal 3D data set with in-plane resolution of 1 × 1.3 was implemented for 10 consecutive measurements each 1.8 seconds apart. The subjects subsequently underwent high spatial-resolution (in-plane: 0.8 × 0.9) CEMRA for comparative analysis. The quality of segmental arterial anatomy and the presence and degree of the arterial stenosis were evaluated by 2 neuroradiologists. The interobserver variability was tested by κ statistics and comparative analysis between the TR-CEMRA and high spatial-resolution CEMRA was evaluated by mean of the Spearman rank correlation coefficient. Results:Craniocervical arteries were visualized with good image quality and definition in the diagnostic range. Occlusive disease was detected in 42 (reader A) and 44 (reader B) arterial segments with excellent interobserver agreement (κ =0.89; 95% confidence interval 0.82–0.96). There was a significant correlation between the TR-CEMRA and high spatial-resolution CEMRA (Rs = 0.91 and 0.93, for readers A and B, respectively) for the degree of stenosis. Three aneurysms, 3 AVMs, 1 AV-fistula, and 2 subclavian steals were detected by both observers and were confirmed by correlative imaging. Conclusion:Time-resolved CEMRA at 3.0 T is reliable and versatile, providing 3-dimensional time-resolved data sets with high spatial (in plane: 1.3 × 1 mm2) and temporal (1.8 seconds) resolution over a large field of view. The higher signal-to-noise ratio gain at 3.0 T can be used effectively to improve performance of fast imaging and to support aggressive parallel acquisition protocols, as in the present study. Further clinical studies are required to establish the range of applications and the accuracy of the technique.