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Biomedical subjects

W J Koroshetz

Publications and source records attributed to W J Koroshetz.

At least 19 recordsLinked to original sources

Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome.

OBJECTIVE: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. BACKGROUND: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. METHODS: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt-Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 degrees C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 degrees C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. RESULTS: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). CONCLUSION: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.

Adult↗

A pilot study of drug-induced hypertension for treatment of acute stroke.

The aim of this pilot study was to determine whether the use of induced hypertension in acute stroke is feasible and associated with neurologic improvement. Phenylephrine was used to raise the systolic blood pressure in patients with acute stroke by 20%, not to exceed 200 mmHG: Of 13 patients treated, 7 improved by 2 points on the NIH Stroke SCALE: No systemic or neurologic complications were seen. The authors conclude that induced hypertension in acute stroke is feasible and likely safe and can improve the neurologic examination in some patients.

Acute Disease↗

Localization of clinical syndromes using DWI: two examples of the "capsular" warning syndrome.

The capsular warning syndrome (CWS) is a subtype of transient ischemic attack characterized by its recurrent nature, absence of cortical signs, and high probability of early capsular stroke. Currently, standard imaging techniques have identified only internal capsule lesions in this entity. The authors present 2 cases with an otherwise typical CWS in whom a brainstem stroke was detected by diffusion-weighted imaging (DWI). DWI's ability to differentiate between acute and chronic infarcts may assist in more accurate localization of clinical syndromes.

Aged↗

Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. METHODS: Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. RESULTS: At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P=0.02) but no significant improvement over algorithms utilizing PWI alone (P=0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P=0.02) or PWI (P=0.04). The performances of thresholding and GLM algorithms were comparable (P>0.2). CONCLUSIONS: Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.

Acute Disease↗

Diffusion-weighted magnetic resonance imaging identifies the "clinically relevant" small-penetrator infarcts.

BACKGROUND: Most patients initially seen with a clinical syndrome consistent with a small-penetrator infarct (SPI) also harbor multiple, chronic, hyperintense, white matter lesions on conventional magentic resonance imaging (ie, T2-weighted image [T2WI] and fluid-attenuation inversion recovery [FLAIR] imaging). Diffusion-weighted imaging (DWI) can identify the clinically relevant "index infarction" in such circumstances, since it differentiates between acute and chronic lesions. OBJECTIVE: To determine the clinical and radiological predictors associated with misidentification of an SPI as acute using T2WI and FLAIR images in patients with an acute SPI seen on DWI. PATIENTS: Sixty-seven consecutive patients who had an SPI. METHODS: Two independent examiners, provided with brief clinical information, but blinded to DWI findings, sought a clinically appropriate lesion on T2WI and FLAIR imaging in 67 consecutive patients found to have an SPI seen on DWI. RESULTS: The index infarction based on evaluation of T2WI or FLAIR images was in a different location than the acute lesion as identified by DWI in 9 (13%) and 11 (16%) of 67 patients, respectively. Both T2WI and FLAIR imaging were rated normal in another 9% of the patients. Multivariate analysis showed that small lesion size (<10 mm) was the only predictor of misidentifying the clinically appropriate lesion on conventional magnetic resonance imaging (P<.01). CONCLUSIONS: T2-weighted imaging and FLAIR imaging fail to identify the clinically relevant SPI in almost one quarter of the patients found to have a lesion on DWI. The characteristics of DWI make it well suited for the detection of acute small infarcts. Diffusion-weighted imaging is necessary to consistently define the clinical-anatomical relations in patients initially seen with SPIs.

Adult↗

Magnetic resonance imaging in acute stroke: clinical perspective.

The efficacy of intravenous (i.v.) and intra-arterial (i.a.) thrombolysis for hyperacute stroke has made "brain attack" a treatable emergency. The addition of ultrafast magnetic resonance imaging (MRI) to acute stroke investigation has both increased our knowledge of acute stroke pathophysiology and brought a tool to study how to best select patients for thrombolytic therapy. MR offers the three essential components: vascular lesion identification, delineation of injured brain tissue, and map of ischemic brain. MR angiography can demonstrate the site of major cerebral artery occlusion, providing a means to screen for i.a. thrombolysis. Diffusion-weighted imaging (DWI) is capable of showing acute ischemic injury within minutes of symptom onset. Perfusion-weighted imaging (PWI) shows the total area of acute ischemia, more accurately reflecting the extent of neurological dysfunction. Combining DWI and PWI immediately gives information that bears on how much tissue is injured (DWI) and how much tissue is functionally inactive but still viable (ischemic on PWI but still normal on DWI). A number of important questions remain, but current knowledge of natural history of stroke with MRI has provided a framework for comparing new therapeutic interventions. Ideally, patient treatment in the future will be tailored not to a fixed time window but to the physiological state of the ischemic tissue as defined by MRI.

Diffusion↗

Combined diffusion-weighted and perfusion-weighted flow heterogeneity magnetic resonance imaging in acute stroke.

BACKGROUND AND PURPOSE: The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size. METHODS: Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning. RESULTS: In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients. CONCLUSIONS: Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies.

Acute Disease↗

Normal diffusion-weighted MRI during stroke-like deficits.

BACKGROUND: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. OBJECTIVE: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. METHODS: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. RESULTS: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). CONCLUSIONS: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.

Aged↗

Riluzole therapy in Huntington's disease (HD).

We conducted a 6-week open-label trial of riluzole (50 mg twice a day) in eight subjects with Huntington's disease. Subjects were evaluated before riluzole treatment, on treatment, and off treatment with the chorea, dystonia, and total functional capacity (TFC) scores from the Unified Huntington's Disease Rating Scale and magnetic resonance spectroscopy measurements of occipital cortex and basal ganglia lactate levels. Adverse events and safety blood and urine tests were assessed throughout the study. All subjects completed the study and riluzole was well tolerated. The age was 45+/-10.2 years (mean +/- standard deviation) and the disease duration was 6.1+/-4.1 years. The chorea rating score improved by 35% on treatment (p = 0.013) and worsened after discontinuation of treatment (p = 0.026). There were no significant treatment effects on the dystonia or TFC scores. The baseline occipital and basal ganglia lactate levels were elevated in all subjects; there was a trend toward lower lactate/creatine ratios during riluzole treatment in the basal ganglia spectra but not in occipital cortex spectra. Additional clinical studies of riluzole for both symptomatic and neuroprotective benefit in Huntington's disease are warranted.

Adult↗

An integrated strategy for evaluation of metabolic and oxidative defects in neurodegenerative illness using magnetic resonance techniques.

The number of physiologic and metabolic phenomena amenable to analysis using magnetic resonance (MR) techniques is increasing every year. MR techniques can now evaluate tissue parameters relevant to TCA cyclemetabolism, anerobic glycolysis, ATP levels, blood-brain barrier permeability, macrophage infiltration, cytotoxic edema, spreading depression, cerebral blood flow and volume, and neurotransmitter function. The paramagnetic nature of certain oxidation states of iron leads to the ability to map out brain function using deoxyhemoglobin as an endogenous contrast agent, and also allows for mapping of local tissue iron concentrations. In addition to these metabolic parameters, the number of ways to generate anatomic contrast using MR is also expanding; and in addition to conventional anatomic scans, mapping of axonal fiber tracts can also be performed using the anisotropy of water diffusion. A strategy for integration of these multifarious parameters in a comprehensive neurofunctional exam in neurodegenerative illness is outlined in this paper. The goals of the integrated exam, as applied to a given neurodegenerative illness, can be subdivided into three categories: etiology, natural history, and therapeutic end points. The consequences of oxidative stress and/or mitochondrial dysfunction are explored in the context of the various parameters that can be measured using the integrated MR exam.

Animals↗

Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset.

PURPOSE: To evaluate the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging performed within 6 hours of the onset of stroke symptoms. MATERIALS AND METHODS: The authors reviewed the patient records and images from all patients hospitalized in a 10-month period in whom diffusion-weighted imaging was performed within 6 hours of the onset of strokelike symptoms (n = 22). Analyses included comparison of the initial interpretation of the diffusion-weighted images with the final clinical diagnosis; blinded reviews of computed tomographic (CT) scans and conventional and diffusion-weighted images; and determination of lesion contrast-to-noise ratios (CNRs). RESULTS: Diffusion-weighted images indicated stroke in 14 patients, all of whom had a final diagnosis of acute stroke. Diffusion-weighted images were negative in eight patients, all of whom had a final clinical diagnosis other than stroke (100% sensitivity, 100% specificity, chi 2 = 23.00, P < .0001). Blinded reviews yielded 100% sensitivity and 86% specificity for diffusion-weighted MR imaging (chi 2 = 15.43, P < .0005); 18% sensitivity and 100% specificity for conventional MR imaging (chi 2 = 2.85, P > .2); and 45% sensitivity and 100% specificity for CT (chi 2 = 4.40, P > .10). Lesion percentage CNRs were 77% for diffusion-weighted imaging, 5.5% for CT, 9.8% for T2-weighted MR imaging, and 3.1% for proton-density-weighted MR imaging (P < .002 for diffusion-weighted imaging vs others). CONCLUSION: Diffusion-weighted MR imaging is highly accurate for diagnosing stroke within 6 hours of symptom onset and is superior to CT and conventional MR imaging.

Aged↗

Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time.

PURPOSE: To investigate additional information provided by maps of relative cerebral blood flow in functional magnetic resonance (MR) imaging of human hyperacute cerebral ischemic stroke. MATERIALS AND METHODS: Diffusion-weighted and hemodynamic MR imaging were performed in 23 patients less than 12 hours after the onset of symptoms. Maps of relative cerebral blood flow and tracer mean tissue transit time were computed, as were maps of apparent diffusion and relative cerebral blood volume. Acute lesion volumes on the maps were compared with follow-up imaging findings. RESULTS: In 15 of 23 subjects (65%), blood flow maps revealed hemodynamic abnormalities not visible on blood volume maps. A mismatch between initial blood flow and diffusion findings predicted growth of infarct more often (12 of 15 subjects with infarcts that grew) than did a mismatch between initial blood volume and diffusion findings (eight of 15). However, lesion volumes on blood volume and diffusion maps correlated better with eventual infarct volumes (r > 0.90) than did those on blood flow and tracer mean transit time maps (r approximately 0.6), likely as a result of threshold effects. In eight patients, blood volume was elevated around the diffusion abnormality, suggesting a compensatory hemodynamic response. CONCLUSION: MR imaging can delineate areas of altered blood flow, blood volume, and water mobility in hyperacute human stroke. Predictive models of tissue outcome may benefit by including computation of both relative cerebral blood flow and blood volume.

Acute Disease↗

Human acute cerebral ischemia: detection of changes in water diffusion anisotropy by using MR imaging.

PURPOSE: To (a) determine the optimal choice of a scalar metric of anisotropy and (b) determine by means of magnetic resonance imaging if changes in diffusion anisotropy occurred in acute human ischemic stroke. MATERIALS AND METHODS: The full diffusion tensor over the entire brain was measured. To optimize the choice of a scalar anisotropy metric, the performances of scalar indices in simulated models and in a healthy volunteer were analyzed. The anisotropy, trace apparent diffusion coefficient (ADC), and eigenvalues of the diffusion tensor in lesions and contralateral normal brain were compared in 50 patients with stroke. RESULTS: Changes in anisotropy in patients were quantified by using fractional anisotropy because it provided the best performance in terms of contrast-to-noise ratio as a function of signal-to-noise ratio in simulations. The anisotropy of ischemic white matter decreased (P = .01). Changes in anisotropy in ischemic gray matter were not significant (P = .63). The trace ADC decreased for ischemic gray matter and white matter (P < .001). The first and second eigenvalues decreased in both ischemic gray and ischemic white matter (P < .001). The third eigenvalue decreased in ischemic gray (P = .001) and white matter (P = .03). CONCLUSION: Gray matter is mildly anisotropic in normal and early ischemic states. However, early white matter ischemia is associated with not only changes in trace ADC values but also significant changes in the anisotropy, or shape, of the water self-diffusion tensor.

Adult↗

Acute stroke: improved nonenhanced CT detection--benefits of soft-copy interpretation by using variable window width and center level settings.

PURPOSE: To assess the use of nonstandard, variable window width and level review settings in computed tomography (CT) without contrast material administration in the detection of acute stroke. MATERIALS AND METHODS: Nonenhanced CT was performed in 21 patients with acute (< 6 hours) middle cerebral arterial stroke and nine control patients. Two blinded neuroradiologists rated all scans for presence of parenchymal hypoattenuation. Images were reviewed at a picture archiving and communication system (PACS) workstation, with standard, locally determined center level and window width settings of 20 and 80 HU and with variable soft-copy settings initially centered at a level of 32 HU with a width of 8 HU. Reviewers altered settings to accentuate gray and white matter contrast. RESULTS: With standard viewing parameters, sensitivity and specificity for stroke detection were 57% and 100%. Sensitivity increased to 71% with variable window width and center level settings, without loss of specificity. Receiver operating characteristic analysis revealed a significant improvement in accuracy with nonstandard, soft-copy review settings (P = .03, one-tailed z test). CONCLUSION: In nonehanced CT of the head, detection of ischemic brain parenchyma is facilitated by soft-copy review with variable window width and center level settings to accentuate the contrast between normal and edematous tissue.

Acute Disease↗

Diffusion-weighted imaging identifies a subset of lacunar infarction associated with embolic source.

BACKGROUND AND PURPOSE: Small infarcts in the territory of penetrator arteries were described as causing a number of distinct clinical syndromes. The vascular pathophysiology underlying such infarcts is difficult to ascertain without careful pathological study. However, the occurrence of multiple, small infarcts, linked closely in time but dispersed widely in the brain, raises the possibility of an embolic mechanism. The current study determines the frequency and clinical characteristics of patients with well-defined lacunar syndromes and the diffusion-weighted imaging (DWI) evidence of multiple acute lesions. METHODS: Sixty-two consecutive patients who presented to the emergency room with a clinically well-defined lacunar syndrome were studied by DWI within the first 3 days of admission. RESULTS: DWI showed multiple regions of increased signal intensity in 10 patients (16%). A hemispheric or brain stem lesion in a penetrator territory that accounted for the clinical syndrome ("index lesion") was found in all. DWI-hyperintense lesions other than the index lesion ("subsidiary infarctions") were punctate and lay within leptomeningeal artery territories in the majority. As opposed to patients with a single lacunar infarction, patients with a subsidiary infarction more frequently (P<0.05) harbored an identifiable cause of stroke. CONCLUSIONS: Almost 1 of every 6 patients presenting with a classic lacunar syndrome has multiple infarctions demonstrated on DWI. This DWI finding usually indicates an identifiable cause of stroke and therefore may influence clinical decisions regarding the extent of etiologic investigations and treatment for secondary prevention.

Adult↗

Diffusion- and perfusion-weighted imaging in vasospasm after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Better measures of cerebral tissue perfusion and earlier detection of ischemic injury are needed to guide therapy in subarachnoid hemorrhage (SAH) patients with vasospasm. We sought to identify tissue ischemia and early ischemic injury with combined diffusion-weighted (DW) and hemodynamically weighted (HW) MRI in patients with vasospasm after SAH. METHODS: Combined DW and HW imaging was used to study 6 patients with clinical and angiographic vasospasm, 1 patient without clinical signs of vasospasm but with severe angiographic vasospasm, and 1 patient without angiographic spasm. Analysis of the passage of an intravenous contrast bolus through brain was used to construct multislice maps of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and tissue mean transit time (tMTT). We hypothesize that large HW imaging (HWI) abnormalities would be present in treated patients at the time they develop neurological deficit due to vasospasm without matching DW imaging (DWI) abnormalities. RESULTS: Small, sometimes multiple, ischemic lesions on DWI were seen encircled by a large area of decreased rCBF and increased tMTT in all patients with symptomatic vasospasm. Decreases in rCBV were not prominent. MRI hemodynamic abnormalities occurred in regions supplied by vessels with angiographic vasospasm or in their watershed territories. All patients with neurological deficit showed an area of abnormal tMTT much larger than the area of DWI abnormality. MRI images were normal in the asymptomatic patient with angiographic vasospasm and the patient with normal angiogram and no clinical signs of vasospasm. CONCLUSIONS: We conclude that DW/HW MRI in symptomatic vasospasm can detect widespread changes in tissue hemodynamics that encircle early foci of ischemic injury. With additional study, the technique could become a useful tool in the clinical management of patients with SAH.

Adult↗