Progression of White Matter Lesion Volume and Health-Related Quality of Life in Patients with Symptomatic Atherosclerotic Disease: The SMART-MR Study

Objectives. Mechanisms influencing the course of physical and mental functioning after an atherosclerotic event are unclear. We examined effects of white matter lesion (WML) activity on changes in functioning in patients with symptomatic atherosclerotic disease. Methods. In 486 patients (58 ± 9 years) of the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, volumetric WML measurements on 1.5T MRI were performed at baseline and 3.9 ± 0.4 years followup. Functioning was assessed with the modified Short-Form 12 (SF-12) questionnaire. Associations of WML progression with changes in functioning were adjusted for age, sex, and vascular risk factors. Results. Physical functioning (baseline: 44, 10th–90th percentile 29–55) improved, whereas mental functioning (baseline: 51, 10th–90th percentile 32–60) declined during followup. WML progression (highest quartile versus rest) contributed to a stronger decline in mental functioning (B = −1.76, 95% CI −3.11 to −0.42), but did not influence changes in physical functioning. Conclusions. Progression of WML volume contributes to a decline in mental functioning in patients with symptomatic atherosclerotic disease

Detection and characterization of small infarcts in the caudate nucleus on 7 Tesla MRI: The SMART-MR study

Small infarcts are among the key imaging features of cerebral small vessel disease (CSVD), but remain largely undetected on conventional MRI. We aimed to evaluate (1) imaging criteria for the detection of small infarcts in the caudate nucleus on 7T MRI, (2) intra- and inter-rater agreement, (3) frequency and (4) detection rate on 7T versus 1.5T MRI. In 90 patients (68 ± 8 years) with a history of vascular disease from the SMART-MR study, we defined 7T imaging criteria for cavitated and non-cavitated small infarcts in the caudate nucleus. In a separate set of 23 patients from the SMART study, intra-rater and inter-rater agreement was excellent for presence, number, and individual locations (Kappa’s, ICCs, and Dice similarity coefficients ranged from 0.85 to 1.00). In the 90 patients, 21 infarcts (20 cavitated) in 12 patients were detected on 7T (13%) compared to 7 infarcts in 6 patients on 1.5T (7%). In conclusion, we established reproducible imaging criteria for the detection of small infarcts in the caudate nucleus on 7T MRI and showed that 7T MRI allows for a higher detection rate than conventional 1.5T MRI. These imaging criteria can be used in future studies to provide new insights into the pathophysiology of CSVD

Intracranial vessel wall lesions on 7T MRI and MRI features of cerebral small vessel disease-The SMART-MR study

The etiology of cerebral small vessel disease (CSVD) is the subject of ongoing research. Although intracranial atherosclerosis (ICAS) has been proposed as a possible cause, studies on their relationship remain sparse. We used 7 T vessel wall magnetic resonance imaging (MRI) to study the association between intracranial vessel wall lesions-a neuroimaging marker of ICAS-and MRI features of CSVD. Within the SMART-MR study, cross-sectional analyses were performed in 130 patients (68 ± 9 years; 88% male). ICAS burden-defined as the number of vessel wall lesions-was determined on 7 T vessel wall MRI. CSVD features were determined on 1.5 T and 7 T MRI. Associations between ICAS burden and CSVD features were estimated with linear or modified Poisson regression, adjusted for age, sex, vascular risk factors, and medication use. In 125 patients, ≥1 vessel wall lesions were found (mean 8.5 ± 5.7 lesions). ICAS burden (per + 1 SD) was associated with presence of large subcortical and/or cortical infarcts (RR = 1.65; 95%CI: 1.12-2.43), lacunes (RR = 1.45; 95% CI: 1.14-1.86), cortical microinfarcts (RR = 1.48; 95%CI: 1.13-1.94), and total white matter hyperintensity volume (b = 0.24; 95%CI: 0.02-0.46). Concluding, patients with a higher ICAS burden had more CSVD features, although no evidence of co-location was observed. Further longitudinal studies are required to determine if ICAS precedes development of CSVD

Vascular Risk Factors of Hippocampal Subfield Volumes in Persons without Dementia: The Medea 7T Study

BACKGROUND: Vascular risk factors have been associated with risk of Alzheimer's disease (AD) and volume loss of the hippocampus, but the associations with subfields of the hippocampus are understudied. Knowing if vascular risk factors contribute to hippocampal subfield atrophy may improve our understanding of vascular contributions to neurodegenerative diseases. OBJECTIVE: To investigate the associations between age, sex, and vascular risk factors with hippocampal subfields volumes on 7T MRI in older persons without dementia. METHODS: From the Medea 7T study, 283 participants (67±9 years, 68% men) without dementia had 7T brain MRI and hippocampal subfield segmentation. Subfields were automatically segmented on the 3D T2-weighted 7T images with ASHS software. Using linear mixed models, we estimated adjusted associations of age, sex, and vascular risk factors with z-scores of volumes of the entorhinal cortex (ERC), subiculum (SUB), Cornu Ammonis (CA)1, CA2, CA3, CA4, and dentate gyrus (DG), and tail as multivariate correlated outcomes. RESULTS: Increasing age was associated with smaller volumes in all subfields, except CA4/DG. Current smoking was associated with smaller ERC and SUB volumes; moderate alcohol use with smaller CA1 and CA4/DG, obesity with smaller volumes of ERC, SUB, CA2, CA3, and tail; and diabetes mellitus with smaller SUB volume. Sex, former smoking, and hypertension were not associated with subfield volumes. When formally tested, no risk factor affected the subfield volumes differentially. CONCLUSION: Several vascular risk factors were associated with smaller volumes of specific hippocampal subfields. However, no statistical evidence was found that subfields were differentially affected by these risk factors

Paroxysmal autonomic instability with dystonia in a patient with tuberculous meningitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report describes an extremely rare combination of paroxysmal autonomic instability with dystonia and tuberculous meningitis. Paroxysmal autonomic instability with dystonia is normally associated with severe traumatic brain injury.</p> <p>Case presentation</p> <p>A 69-year-old man of Indonesian descent was initially suspected of having a community-acquired pneumonia, which was seen on chest X-ray and computed tomography of the chest. However, a bronchoscopy showed no abnormalities. He was treated with amoxicillin-clavulanic acid in combination with ciprofloxacin. However, nine days after admission he was disorientated and complained of headache. Neurological examination revealed no further abnormalities. A lumbar puncture revealed no evidence of meningitis. He was then transferred to our hospital. At that time, initial cultures of bronchial fluid for <it>Mycobacterium tuberculosis </it>turned positive, as well as polymerase chain reaction for <it>Mycobacterium tuberculosis</it>. Later, during his stay in our intensive care unit, he developed periods with hypertension, sinus tachycardia, excessive transpiration, decreased oxygen saturation with tachypnea, pink foamy sputum, and high fever. This constellation of symptoms was accompanied by dystonia in the first days. These episodes lasted approximately 30 minutes and improved after administration of morphine, benzodiazepines or clonidine. Magnetic resonance imaging showed an abnormal signal in the region of the hippocampus, thalamus and the anterior parts of the lentiform nucleus and caudate nucleus.</p> <p>Conclusions</p> <p>In patients with (tuberculous) meningitis and episodes of extreme hypertension and fever, paroxysmal autonomic instability with dystonia should be considered.</p

Quantitative assessment of brachial plexus MRI for the diagnosis of chronic inflammatory neuropathies

OBJECTIVE: This study aimed at developing a quantitative approach to assess abnormalities on MRI of the brachial plexus and the cervical roots in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) and to evaluate interrater reliability and its diagnostic value. METHODS: We performed a cross-sectional study in 50 patients with CIDP, 31 with MMN and 42 disease controls. We systematically measured cervical nerve root sizes on MRI bilaterally (C5, C6, C7) in the coronal [diameter (mm)] and sagittal planes [area (mm2)], next to the ganglion (G0) and 1 cm distal from the ganglion (G1). We determined their diagnostic value using a multivariate binary logistic model and ROC analysis. In addition, we evaluated intra- and interrater reliability. RESULTS: Nerve root size was larger in patients with CIDP and MMN compared to controls at all predetermined anatomical sites. We found that nerve root diameters in the coronal plane had optimal reliability (intrarater ICC 0.55-0.87; interrater ICC 0.65-0.90). AUC was 0.78 (95% CI 0.69-0.87) for measurements at G0 and 0.81 (95% CI 0.72-0.91) for measurements at G1. Importantly, our quantitative assessment of brachial plexus MRI identified an additional 10% of patients that showed response to treatment, but were missed by nerve conduction (NCS) and nerve ultrasound studies. CONCLUSION: Our study showed that a quantitative assessment of brachial plexus MRI is reliable. MRI can serve as an important additional diagnostic tool to identify treatment-responsive patients, complementary to NCS and nerve ultrasound

Lipidomics Reveals Multiple Pathway Effects of a Multi-Components Preparation on Lipid Biochemistry in ApoE*3Leiden.CETP Mice

Background: Causes and consequences of the complex changes in lipids occurring in the metabolic syndrome are only partly understood. Several interconnected processes are deteriorating, which implies that multi-target approaches might be more successful than strategies based on a limited number of surrogate markers. Preparations from Chinese Medicine (CM) systems have been handed down with documented clinical features similar as metabolic syndrome, which might help developing new intervention for metabolic syndrome. The progress in systems biology and specific animal models created possibilities to assess the effects of such preparations. Here we report the plasma and liver lipidomics results of the intervention effects of a preparation SUB885C in apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) mice. SUB885C was developed according to the principles of CM for treatment of metabolic syndrome. The cannabinoid receptor type 1 blocker rimonabant was included as a general control for the evaluation of weight and metabolic responses. Methodology/Principal Findings: ApoE*3Leiden.CETP mice with mild hypercholesterolemia were divided into SUB885C-, rimonabant- and non-treated control groups. SUB885C caused no weight loss, but significantly reduced plasma cholesterol (-49%, p <0.001), CETP levels (-31%,

Osteochondral lesion depth on MRI can help predict the need for a sandwich procedure

Purpose Autologous subchondral bone grafting in combination with autologous chondrocyte implantation (ACI) (sandwich procedure) is a well-accepted procedure for the treatment of osteochondral lesions of the knee. This requires a different surgical technique and preoperative planning compared to ACI alone. In addition, pain from bone marrow donor site locations can be expected and should be part of patient consent and expectations. This study evaluates whether the MRI made as part of the standard preoperative cartilage patient work up has the diagnostic accuracy to predict the need for a sandwich procedure. Methods and materials Retrospectively, 185 preoperative MRI scans (PD and T2 sequences) of patients planned for ACI were included. The integrity of the subchondral bone and lamina was scored by four different observers (3 radiologists, and 1 orthopaedic resident). The depth of the defect was measured perpendicular from articulating surface to the bottom of the bony lesion. The area under the curve (AUC) for subchondral defect on MRI (i.e. lamina or bone defect or expert impression), depth measurements and eventual sandwich procedure were calculated. Also inter-observer Kappa values were determined. Results The AUCs for lamina (0.74–0.80) and bone defect (0.73–0.79) were fair and inter-observer Kappas ranged from 0.49 to 0.76, indicating a moderate-good inter-observer agreement and moderate prediction of the need for a sandwich procedure based on the presence of lamina and or subchondral bone defect on MRI. However, depth measurements resulted in an AUC of 0.90 (95% CI: 0.84–0.95,) with an optimal cut-off point at 6.5 mm depth of the lesion (90% sensitivity, 80% specificity) to predict the need for a sandwich procedure. Conclusion Ours is the first study examining MRI as a diagnostic tool in predicting the need for a sandwich procedure. Our results show that the integrity of the subchondral layer on MRI has a moderate role in predicting the need for an eventual autologous bone graft to augment ACI whereas in our cohort a depth of the lesion above 6.5 mm accurately predicts the need for a sandwich procedure. This can aid in optimising the preoperative planning and patient consent

The association between intraoperative hyperglycemia and cerebrovascular markers

BACKGROUND AND PURPOSE: Hyperglycemia can lead to an increased rate of apoptosis of microglial cells and to damaged neurons. The relation between hyperglycemia and cerebrovascular markers on MRI is unknown. Our aim was to study the association between intraoperative hyperglycemia and cerebrovascular markers. METHODS: In this further analysis of a subgroup investigation of the BIOCOG study, 65 older non-demented patients (median 72 years) were studied who underwent elective surgery of >= 60 minutes. Intraoperative blood glucose maximum was determined retrospectively in each patient. In these patients, preoperatively and at 3 months follow-up a MRI scan was performed and white matter hyperintensity (WMH) volume and shape, infarcts, and perfusion parameters were determined. Multivariable logistic regression analyses were performed to determine associations between preoperative cerebrovascular markers and occurrence of intraoperative hyperglycemia. Linear regression analyses were performed to assess the relation between intraoperative hyperglycemia and pre- to postoperative changes in WMH volume. Associations between intraoperative hyperglycemia and postoperative WMH volume at 3 months follow-up were also assessed by linear regression analyses. RESULTS: Eighteen patients showed intraoperative hyperglycemia (glucose maximum >= 150 mg/dL). A preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia [convexity: OR 33.318 (95 % CI (1.002 - 1107.950); p = 0.050]. Other preoperative cerebrovascular markers were not related to the occurrence of intraoperative hyperglycemia. Intraoperative hyperglycemia showed no relation with pre- to postoperative changes in WMH volume nor with postoperative WMH volume at 3 months follow-up. CONCLUSIONS: We found that a preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia. These findings may suggest that a similar underlying mechanism leads to a certain pattern of vascular brain abnormalities and an increased risk of hyperglycemia

Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke