Acute Toxic Leukoencephalopathy: Etiologies, Imaging Findings, and Outcomes in 101 Patients.

BACKGROUND AND PURPOSE: Prior studies regarding acute toxic leukoencephalopathy (ATL) are either small, or preliminary. Our aim was to evaluate etiologies of and differences in imaging severity and outcomes among various etiologies of ATL. MATERIALS AND METHODS: MRIs of patients with suspected ATL over 15 years were retrospectively reviewed; inclusion criteria were: MRI <3 weeks of presentation with both DWI and FLAIR. These were jointly graded by two neuroradiologists via a previously described score of severity. Clinical outcome was evaluated via both modified Rankin (mRS) and ATL outcome (ATLOS) scores, each being correlated with the DWI and FLAIR scores. Etiologic subgroups of n > 6 patients were statistically compared. RESULTS: Of 101 included patients, the 4 subgroups of n > 6 were the following: chemotherapy (n = 35), opiates (n = 19), acute hepatic encephalopathy (n = 14), and immunosuppressants (n = 11). Other causes (n = 22 total) notably included carbon monoxide (n = 3) metronidazole (n = 2), and uremia (n = 1). The mean DWI/FLAIR severity scores were 2.6/2.3, 3.3/3.3, 2.1/2.1 and 2.0/2.5 for chemotherapeutics, opiates, AHE and immunosuppressants, respectively, with significant differences in both imaging severity and outcome (P = .003-.032) among subgroups, particularly immunosuppressant versus chemotherapy-related ATL and immunosuppressants versus opiates (P = .004-.032) related ATL. DWI and FLAIR severity weakly correlated with outcome (ρ = 0.289-.349, P < .005) but correlated stronger in the chemotherapy (ρ = 0.460-.586, P < .010) and opiate (ρ =.472-.608, P < .05) subgroups, which had the worst outcomes. ATL clinically resolved in 36%, with severe outcomes in 23% (coma or death, 9/16 deaths from fludarabine). Notable laboratory results were elevated CSF myelin basic protein levels in 8/9 patients and serum blood urea nitrogen levels in 24/91. CONCLUSIONS: Clinical outcomes of ATL vary on the basis of etiology, being worse in chemotherapeutic- and opiate-related ATL. Uremia may be a predisposing or exacerbating factor.

Susceptible vessel sign: identification of arterial occlusion and clinical implications in acute ischaemic stroke.

AIM: To determine the accuracy of the susceptible vessel sign (SVS) in the detection of arterial occlusion and its clinical implication in acute ischaemic stroke. MATERIALS AND METHODS: Consecutive ischaemic stroke patients who underwent magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) within 24 hours of symptom onset or time last-seen-well were included. Two independent neuroradiologists reviewed the SWI for evidence of the SVS. Admission stroke severity was determined by the National Institute of Health Stroke Scale (NIHSS) scores, and poor clinical outcome was defined by a 3-months modified Rankin scale (mRS) score >2. RESULTS: The SVS was identified in 26 (12%) of 213 patients with substantial inter-reviewer agreement. The SVS had 99% specificity, 88% negative predictive value (NPV), 51% sensitivity, and 92% positive predictive value (PPV) for detection of acute arterial occlusions. In consecutive stroke patients, the presence of SVS was associated with higher admission NIHSS scores (median 9 versus 3, p<0.001), arterial occlusion (92% versus 12%, p<0.001), larger infarct volume (162±180 ml versus 25±48 ml, p=0.001), and higher rate of poor clinical outcome at 3-months follow-up (58% versus 25%, p=0.001). In the subset of patients with acute arterial occlusion (n=47), the SVS was associated with higher admission NIHSS scores (median of 10 versus 3, p=0.038) and larger infarct volumes (173±184 ml versus 76±112 ml, p=0.034). CONCLUSIONS: The SVS is a highly specific sign of occlusive arterial thrombus, and is associated with larger infarct volume and more severe presentation in a series of consecutive stroke patients, as well as in the subgroup of patients with acute arterial occlusion.

CT Perfusion in Acute Lacunar Stroke: Detection Capabilities Based on Infarct Location.

BACKGROUND AND PURPOSE: Recent studies demonstrated superiority of CTP to NCCT/CTA at detecting lacunar infarcts. This study aimed to assess CTP's capability to identify lacunae in different intracranial regions. MATERIALS AND METHODS: Over 5.5 years, 1085 CTP examinations were retrospectively reviewed in patients with acute stroke symptoms with CTP within 12 hours and MRI within 7 days of symptom onset. Patients had infarcts ≤2 cm or no acute infarct on DWI; patients with concomitant infarcts >2 cm on DWI were excluded. CTP postprocessing was automated by a delay-corrected algorithm. Three blinded reviewers were given patient NIHSS scores and symptoms; infarcts were recorded based on NCCT/CTA, CTP (CBF, CBV, MTT, and TTP), and DWI. RESULTS: One hundred thirteen patients met inclusion criteria (53.1% female). On DWI, lacunar infarcts were present in 37 of 113 (32.7%), and absent in 76 of 113 (67.3%). On CTP, lacunar infarcts typically appeared as abnormalities larger than infarct size on DWI. Interobserver κ for CTP ranged from 0.38 (CBF) (P < .0001) to 0.66 (TTP) (P < .0001); interobserver κ for DWI was 0.88 (P < 0.0001). In all intracranial regions, sensitivity of CTP ranged from 18.9% (CBV) to 48.7% (TTP); specificity ranged from 97.4% (CBF and TTP) to 98.7% (CBV and MTT). CTP's sensitivity was highest in the subcortical white matter with or without cortical involvement (21.7%-65.2%) followed by periventricular white matter (12.5%-37.5%); sensitivity in the thalami or basal ganglia was 0%. CONCLUSIONS: CTP has low sensitivity and high specificity in identifying lacunar infarcts. Sensitivity is highest in the subcortical white matter with or without cortical involvement, but limited in the basal ganglia and thalami.

Acute CT perfusion changes in seizure patients presenting to the emergency department with stroke-like symptoms: correlation with clinical and electroencephalography findings.

AIM: To determine acute computed tomography perfusion (CTP) changes in seizure patients presenting with stroke-like symptoms and to correlate those changes with clinical presentation and electroencephalography (EEG). MATERIALS AND METHODS: The medical records of all patients who presented to the emergency department with acute stroke-like symptoms and underwent CTP (n=1085) over a 5.5-year period were reviewed. Patients were included who had primary seizure as the final diagnosis, and underwent CTP within 3 hours of symptom onset. A subset of patients had a follow-up EEG within 7 days. The perfusion changes and EEG findings were compared between different clinical presentations. RESULTS: Eighteen of 1085 patients (1.7%) who underwent CTP following an acute stroke-like presentation were included. The abnormality on CTP was usually focal, unilateral hyperperfusion - increased relative cerebral blood flow (rCBF) and volume (rCBV) (n=14/18), which most often affected the temporal lobe. Those patients who presented with a motor or speech deficit (n=12) had a higher temporal lobe rCBV, and rCBF, and lower relative mean transit time (rMTT) compared to those with non-focal neurological deficit at presentation. Early EEG was available in 13 patients; a sharp-spike epileptiform EEG discharge pattern (n=5) was associated with higher temporal lobe ipsilateral rCBF and rCBV, and lower rMTT on admission CTP examination. CONCLUSION: Seizure patients who present with a unilateral motor or speech deficit most commonly have contralateral hyperperfusion in the corresponding eloquent brain regions on the acute-stage CTP examination. In such patients, epileptiform discharges on the early follow-up EEG are associated with ipsilateral hyperperfusion on the admission CTP.

Water proton MR properties of human blood at 1.5 Tesla: magnetic susceptibility, T(1), T(2), T*(2), and non-Lorentzian signal behavior.

Accurate knowledge of the magnetic properties of human blood is required for the precise modeling of functional and vascular flow-related MRI. Herein are reported determinations of the relaxation parameters of blood, employing in vitro samples that are well representative of human blood in situ. The envelope of the blood (1)H(2)O free-induction decay signal magnitude during the first 100 msec following a spin echo at time TE is well- described empirically by an expression of the form, S(t) = S(o). exp[-R(*)(2). (t - TE) - AR*. (t - TE)(2)]. The relaxation parameters AR* and R(*)(2) increase as a function of the square of the susceptibility difference between red blood cell and plasma and depend on the spin-echo time. The Gaussian component, AR*, should be recognized in accurate modeling of MRI phenomena that depend upon the magnetic state of blood. The magnetic susceptibility difference between fully deoxygenated and fully oxygenated red blood cells at 37 degrees C is 0.27 ppm, as determined independently by MR and superconducting quantum interference device (SQUID) measurements. This value agrees well with the 1936 report of Pauling and Coryell (Proc Natl Acad Sci USA 1936;22:210-216), but is substantially larger than that frequently used in MRI literature. Magn Reson Med 45:533-542, 2001.

Structural homology of spinach acyl carrier protein and Escherichia coli acyl carrier protein based on NMR data.

Acyl carrier proteins (ACPs) from spinach and from Escherichia coli have been used to demonstrate the utility of proton NMR for comparison of homologous structures. The structure of E. coli ACP had been previously determined and modeled as a rapid equilibrium among multiple conformational forms (Kim and Prestegard, Biochemistry 28:8792-8797, 1989). Spinach ACP showed two slowly exchanging forms and could be manipulated into one form for structural study. Here we compare this single form to postulated multiple forms of E. coli ACP using the limited amount of NOE data available for the spinach protein. A number of long-range NOE contacts were present between homologous residues in both spinach and E. coli ACP, suggesting tertiary structural homology. To allow a more definitive structural comparison, a method was developed to use spinach ACP NOE constraints to search for regions of structural divergence from two postulated forms of E. coli ACP. The homologous regions of the two protein sequences were aligned, additional distance constraints were extracted from the E. coli structure, and these were mapped onto the spinach sequence. These distance constraints were combined with experimental NOE constraints and a distance geometry simulated annealing protocol was used to test for compatibility of the constraints. All of the experimental spinach NOE constraints could be successfully combined with the E. coli data, confirming the general hypothesis of structural homology. A better fit was obtained with one form, suggesting a preferential stabilization of that form in the spinach case.