Cerebral Hemodynamics in Patients with Hemolytic Uremic Syndrome Assessed by Susceptibility Weighted Imaging and Four-Dimensional Non-Contrast MR Angiography

<div><p>Background and Purpose</p><p>Conventional magnetic resonance imaging (MRI) of patients with hemolytic uremic syndrome (HUS) and neurological symptoms performed during an epidemic outbreak of Escherichia coli O104:H4 in Northern Europe has previously shown pathological changes in only approximately 50% of patients. In contrast, susceptibility-weighted imaging (SWI) revealed a loss of venous contrast in a large number of patients. We hypothesized that this observation may be due to an increase in cerebral blood flow (CBF) and aimed to identify a plausible cause.</p><p>Materials and Methods</p><p>Baseline 1.5T MRI scans of 36 patients (female, 26; male, 10; mean age, 38.2±19.3 years) were evaluated. Venous contrast was rated on standard SWI minimum intensity projections. A prototype four-dimensional (time resolved) magnetic resonance angiography (4D MRA) assessed cerebral hemodynamics by global time-to-peak (TTP), as a surrogate marker for CBF. Clinical parameters studied were hemoglobin, hematocrit, creatinine, urea levels, blood pressure, heart rate, and end-tidal CO₂.</p><p>Results</p><p>SWI venous contrast was abnormally low in 33 of 36 patients. TTP ranged from 3.7 to 10.2 frames (mean, 7.9 ± 1.4). Hemoglobin at the time of MRI (n = 35) was decreased in all patients (range, 5.0 to 12.6 g/dL; mean, 8.2 ± 1.4); hematocrit (n = 33) was abnormally low in all but a single patient (range, 14.3 to 37.2%; mean, 23.7 ± 4.2). Creatinine was abnormally high in 30 of 36 patients (83%) (range, 0.8 to 9.7; mean, 3.7 ± 2.2). SWI venous contrast correlated significantly with hemoglobin (r = 0.52, P = 0.0015), hematocrit (r = 0.65, P < 0.001), and TTP (r = 0.35, P = 0.036). No correlation of SWI with blood pressure, heart rate, end-tidal CO₂, creatinine, and urea level was observed. Findings suggest that the loss of venous contrast is related to an increase in CBF secondary to severe anemia related to HUS. SWI contrast of patients with pathological conventional MRI findings was significantly lower compared to patients with normal MRI (mean SWI score, 1.41 and 2.05, respectively; P = 0.04). In patients with abnormal conventional MRI, mean TTP (7.45), mean hemoglobin (7.65), and mean hematocrit (22.0) were lower compared to patients with normal conventional MRI scans (mean TTP = 8.28, mean hemoglobin = 8.63, mean hematocrit = 25.23).</p><p>Conclusion</p><p>In contrast to conventional MRI, almost all patients showed pathological changes in cerebral hemodynamics assessed by SWI and 4D MRA. Loss of venous contrast on SWI is most likely the result of an increase in CBF and may be related to the acute onset of anemia. Future studies will be needed to assess a possible therapeutic effect of blood transfusions in patients with HUS and neurological symptoms.</p></div

Rating scale for SWI venous contrast.

<p>1 –no veins visualized, 2 –medium contrast of cortical veins (arrow), no deep veins, 3 –good contrast of cortical veins, medium contrast of deep veins (arrows), 4 –relatively preserved venous contrast (arrows).</p

Results of statistical analysis.

<p>SWI venous contrast correlated significantly with hemoglobin, hematocrit, and TTP. TTP correlated significantly with hemoglobin and hematocrit.</p

Patient examples.

<p>(A) SWI minimum intensity projection image, (B) 4D visualization of local inflow time-to-peak (TTP) and (C) global inflow curve depicting the global TTP. The first patient (top row) with good SWI venous contrast is a 21-year-old female (P07; SWI score, 4; etCO_<i>2</i> = 30 mmHg) showing shorter TTP by 4D MRA. Patient 2 (bottom row), a 20-year-old female (P14; SWI score, 1; etCO_<i>2</i> = 40 mmHg), shows decreased venous contrast on SWI and prolonged TTP. <i>Note</i>: <i>a</i>.<i>u</i>. <i>= arbitrary units</i>.</p

Scoring of SWI venous contrast.

<p>Scoring of SWI venous contrast.</p

Neurophysiological and MRI data 4

The files contain neurophysiological and MRI (T2 weighted MRI, Diffusion Tensor Imaging) data from 20 patients with primary biliary cholangitis and 20 controls

Neurophysiological and MRI data 3

The files contain neurophysiological and MRI (T2 weighted MRI, Diffusion Tensor Imaging) data from 20 patients with primary biliary cholangitis and 20 controls

Neurophysiological and MRI data 1

The files contain neurophysiological and MRI (T2 weighted MRI, Diffusion Tensor Imaging) data from 20 patients with primary biliary cholangitis and 20 controls

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure

<div><p>Background</p><p>In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance.</p><p>Methods</p><p>20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance.</p><p>Results</p><p>Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance.</p><p>Conclusions</p><p>Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.</p></div

Neuropsychological assessment.

<p>Neuropsychological assessment.</p