Identifying diagnostic and prognostic factors in cerebral amyloid angiopathy-related inflammation: A systematic analysis of published and seven new cases.

The objective of this study was to evaluate the effect of intra-articular corticosteroid injection (IACI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal (HPA) axis in patients with osteoarthritis of the knee. Patients with symptomatic osteoarthritis of the knee who failed to respond to nonsteroidal anti-inflammatory medications and physical therapy were randomized between group 1 and group 2. Group 1 patients had an IACI of 80mg of MPA at the knee joint and group 2 patients had an intra-articular injection (IAI) of 6ml (60mg) of sodium hyaluronate (control group). Immediately prior to the IAI and on weeks 1, 2, 3, 4, and 8 following IAI, patients from both groups underwent a low-dose (1μg) adrenocorticotropin hormone (ACTH) stimulation test. Demographic, clinical, laboratory, and radiologic variables were documented in all patients. Both criteria of <7μg/dl increase in the serum cortisol level and absolute levels of <18μg/dl 30min following the ACTH stimulation test were used to define secondary adrenal insufficiency (SAI). Twenty patients were randomized in each group. In group 1, 25% of patients had SAI vs. none in group 2 (p = 0.0471). The earliest SAI was observed at week 2, and latest SAI was observed at week 4. SAI was observed at one time point, two consecutive time points, or two separate time points in the same patient. There was no correlation between SAI and any of the demographic, clinical, or laboratory variables. An IACI of 80mg MPA at the knee joint induced a transient SAI in 25% of the patients, an effect that was observed between week 2 and week 4 following the IACI.

Purpose: Multiple Sclerosis (MS) is an acute, autoimmune, and inflammatory disease in the central nervous system. This study investigated the effect of sagittal Short Tau Inversion Recovery (STIR) and T2-W Fluid Attenuated Inversion Recovery (FLAIR) sequences rather than sagittal T2-W as complementary sequences in patients with cervical spinal cord lesions and suspected MS.&#x0D; Materials and Methods: This cross-sectional study was performed on all individuals referred to the Shahid Ghazi MRI center in Sanandaj for six months. Sixty patients with a cervical spine MRI request that were suspected of having MS were examined. The number of MS plaques in the sagittal T2-W FSE, sagittal STIR, and sagittal T2-W FLAIR were recorded separately. A comparison between routine sequences and sequence supplementation has been made for characterizing MS plaque in the spine.&#x0D; Results: Results showed that the greatest agreement was related to sagittal STIR, and sagittal FLAIR (Cohen’s kappa = 0.56). Whereas the least agreement values were from sagittal T2-W and sagittal FLAIR, STIR and FLAIR, T2-W and FLAIR, T2-W and STIR (Cohen’s kappa = 0.20, 0.33, 0.48, 0.55), respectively. Sagittal STIR and sagittal FLAIR were excellent predictors for MS plaques diagnosis due to the area under the ROC curve = 0.56; sensitivity (95% CI) = [0.85 (0.73426 to 0.929044)] and specificity (95% CI) = [0.46 (0.336699 to 0.600035)].&#x0D; Conclusion: Results show that FLAIR T2-W images in sagittal sequence are appropriate for detecting lesions around spinal cord lesions. Furthermore, using thresholds obtained via statistical analysis, plaques in the cervical spinal cord can be identified in sagittal STIR images.

Central venous catheterization is a fundamental component in delivering haemodialysis yet is associated with significantly higher complication rates than other methods of vascular access. In this study, we report results of univariate and multivariate analyses designed to identify and quantify independent risk association for catheterization type, clinical variables and laboratory variables with regard to the development of catheter-related bacteraemia (CRB) and catheter failure due to poor haemodialysis flow. A 2-year prospective study of all incident haemodialysis vascular access catheter insertions was conducted. Laboratory and clinical variables were recorded at catheter insertion, and the clinical course was followed up to the point of catheter removal. CRB and catheter failure due to poor flow were recorded as outcome events. Univariate and multivariate analyses were used to test for association between clinical and laboratory variables and outcome. Forty-four thousand five hundred seventy-six catheter days were accumulated over the study period. Multivariate analysis demonstrated an independent association between non-tunnelled catheterization procedures and adverse outcomes compared with tunnelled central venous catheter insertions. Elevated modified Charlson comorbidity score was independently associated with the development of CRBc. Elevated C-reactive protein and low haemodialysis blood pump flow were independently associated with catheter failure due to poor flow. The data demonstrate that tunnelled central venous catheter insertions have an association with lower complication rates than non-tunnelled central venous catheter insertions that is independent of whether patients have acute or chronic renal failure, or high levels of comorbidity.

The aim of our study is to evaluate the diagnostic accuracy of double inversion recovery (DIR) in detection of multiple sclerosis (MS) lesions as well as the correlation between the expanded disability status scale (EDSS) and lesion load measurement detected by DIR, fluid attenuated inversion recovery (FLAIR) and T2 weighted imaging (T2WI) in order to reveal the essential role of DIR sequence in assessing clinical inability as a practicable experiment. A total of 97 patients were assessed on a 3T Siemens Skyra MRI scanner using DIR, FLAIR, and T2W_TSE sequences. EDSS was used to assess the physical disability in patients with MS. The diagnostic accuracy of DIR, FLAIR and T2WI sequences was also determined in different anatomical regions. Sensitivity and specificity were assessed by relative operating characteristics/ receiver operating characteristics (ROC) curve at different cut off points. Spearman correlation was applied to identify the significant relationships between the number of lesions displayed by DIR, FLAIR and T2WI at different regions and EDSS score. Our results pointed out the highest sensitivity (92.9%) and specificity (73.5%) for the number of lesions in infratentorial region at the cut-off point of 4.5 and the highest correlation between the number of lesions and EDSS was observed in infratentorial region (r= 0.584, p&lt;0.001) for DIR sequence. According to the findings of ROC analysis, the number of lesions detected by DIR technique in the infratentorial region is the best predictor of EDSS as a gold standard. DIR can be used as a complementary technique comparing to conventional T2 and FLAIR sequences and describe physical and cognitive dysfunction as well. Due to the higher potential of the DIR sequence to reveal a greater number of MS lesions and to overcome the technical defect of conventional MRI sequences in the diagnosis of cortical lesions, it is recommended that DIR sequences be routinely added to MRI imaging protocols for patients with MS.

The objective of the study was to examine the utility of double inversion recovery (DIR) magnetic resonance imaging (MRI) using a 3-T magnetic resonance imager in the preoperative evaluation of hippocampal sclerosis (HS) in patients with mesial temporal lobe epilepsy. This retrospective study had institutional review board approval, and informed consent was obtained. Twelve patients with unilateral HS and 12 age-matched healthy control subjects were included. Imaging was performed using DIR, fluid-attenuated inversion recovery (FLAIR), and T2-weighted turbo spin-echo (T2 TSE) sequences vertical to the hippocampal axis. Quantitative assessment for hippocampus of the patients and control subjects was determined. Regions of interest (ROIs) were placed on bilateral hippocampi, and signal intensity was measured. The signal-to-noise ratio (SNR) of ipsilateral hippocampus, contrast ratio of ipsilateral-to-contralateral side, contrast-to-noise ratio (CNR), and asymmetry index of bilateral hippocampi were calculated and compared among the 3 sequences. Statistical analyses were performed with 1-way analysis of variance and Student t test. On DIR images, HS demonstrated extremely high signal intensity. The hippocampi ipsilateral to the seizure focus showed significantly increased signal intensity, as compared with contralateral hippocampi and healthy subjects (F = 47.876, P < 0.001). The higher SNR of ipsilateral hippocampus on DIR was significant compared with the FLAIR and T2 TSE (P < 0.01). The CNR of bilateral hippocampi on DIR was also significantly higher than that on the FLAIR and T2 TSE (P < 0.01). However, compared with the FLAIR, no significant differences of contrast ratio and asymmetry index between bilateral hippocampi were observed on DIR. Double inversion recovery brain imaging reveals characteristically extremely high signal intensity of hippocampus in patients with HS. Double inversion recovery images can describe HS with high SNR and CNR superior to conventional magnetic resonance sequences and can be valuable for the diagnosis of HS.

Background Ring-enhancing lesion is one of the most common radiological findings in a spectrum of diseases affecting the central nervous system (CNS) including infectious, inflammatory, demyelinating, and neoplastic pathologies. Objective The aim of this study was to analyze the clinical and radiological parameters of pathologies presenting as ring-enhancing lesions in the brain, especially tuberculoma and neurocysticercosis. Materials and Methods In this study, 58 patients with ring-enhancing lesions on brain magnetic resonance imaging (MRI) were recruited. Cases were studied for different clinical and radiological variables. Data were analyzed using SPSS 20 version. Results Tuberculoma is the most common pathology accounting for ring-enhancing lesions in the brain, followed by neurocysticercosis. Seizures were present in the majority of cases, with focal onset seizures being more common than generalized seizures. Multiple ring-enhancing lesions were present in the majority of cases, with the cerebral cortex being the most frequently involved site. On T2 fluid-attenuated inversion recovery (FLAIR) sequence, 2/3rds of the neurocysticercosis cases showed full suppression, whereas only 1/10th of tuberculoma cases showed full suppression. On diffusion-weighted imaging (DWI), a minority of neurocysticercosis cases showed diffusion restriction, while more than one-fifth of tuberculoma cases showed diffusion restriction. MR spectroscopy (MRS) results showed that a normal lipid lactate peak was observed in the majority of neurocysticercosis cases, whereas more than half of tuberculoma cases had a high lipid lactate peak. The choline-to-creatine ratio (Chol/Cre ratio) was less than 1.2 in one-third of neurocysticercosis cases and between 1.2 and 2.0 in two-thirds of the cases. In contrast, more than half of tuberculoma cases showed a Chol/Cre ratio between 1.2 and 2.0. Conclusion Tuberculoma and NCC are the two most common causes of ring-enhancing lesions in developing world. Radiological characteristics like FLAIR suppression and diffusion restriction on MRI and Chol/Cre ratio and lipid peak on MRS can substantiate the clinical parameters in distinguishing the two pathologies to a good extent.

Introduction: Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging and invasive hemodynamic assessment is not easily available. A non-invasive tool for prediction of elevated PCWP could facilitate earlier identification of HFpEF and reduce the need for right heart catheterization (RHC). Methods: We analyzed 279 patients from the JHU HFpEF Clinic who underwent RHC. Patients were separated by PCWP (≥15 mmHg versus &lt;15 mmHg) and compared clinical, laboratory, and echocardiographic variables, including the H2PEF score. Five feature sets were defined: (1) clinical, laboratory, and echocardiographic variables; (2) echocardiographic variables only; (3) clinical and laboratory variables only; (4) H2PEF score alone; and (5) E/e′ ratio alone. Categorical variables were one-hot encoded; continuous variables were standardized. Feature selection used correlation with PCWP and AUC-based forward-backward optimization. Five classifiers were trained and evaluated using cross-validated and test-set AUC, with performance compared using DeLong’s test. Results: All models showed moderate to high discrimination with test set AUCs ranging from 0.65 to 0.84 (P &lt; 0.001; Figure A ). The top-performing model used only clinical and laboratory variables, achieving AUC of 0.84, outperforming the other models though differences were not statistically significant. In contrast, traditional diagnostic tools—the H2PEF score and E/e′ ratio—performed worse (AUCs both 0.58), with significant differences in DeLong comparisons (z = 3.72, P &lt; 0.001 and z = 3.31, P &lt; 0.001). Key clinical predictors in the highest performing model were diabetes, hypertension, NT-proBNP, ferritin, and cystatin C, along with E/e′, LA diameter, and LVMI ( Figure B ). Conclusion: Machine learning models built on routinely available clinical, laboratory and echo data can accurately predict elevated PCWP in HFpEF and outperform existing diagnostic tools such as the H2PEF score. Such models can serve as effective surrogates for invasive hemodynamic assessment in HFpEF; prospective validation is needed in the future.

Previous studies have suggested that disease duration in Creutzfeldt-Jakob disease (CJD) may be related to the radiological findings or cerebrospinal fluid (CSF) tau levels; however, it is not yet established whether clinical, radiological, and laboratory findings at diagnosis can predict survival or have a prognostic value. The aim of this study was to examine whether the disease duration is correlated with clinical, radiological, and laboratory variables. The study population consisted of consecutive familial CJD (fCJD) patients that were assessed within 1week from the diagnosis including the CJD neurological scale (CJD-NS), Minimental Status Examination, Frontal Assessment Battery, NIH Stroke Scale, and the expanded disability status scale. In addition, a single MRI study was done and measurements of the extent of the cortical and subcortical involvement were performed. CSF was examined as part of the workout, and tau levels were determined. Sixty-nine fCJD patients were included in the study (43 males, mean age 59.3 ± 8.4, range 44-79years). The mean disease duration was 7.3 ± 6.9months (median 5.6months, range 2-20months). A significant correlation was found between the disease duration and the CJD-NS, the disease burden as reflected by the degree of cortical involvement by DWI, and the CSF tau levels. The findings of the current study reveal that several findings at disease onset including the disease severity, the cortical changes, and the tau levels are each individually correlated with disease duration and can be used by the clinician as a tool to predict the disease course and prognosis.

Diffusion-weighted imaging (DWI) - fluid attenuated inversion recovery (FLAIR) mismatch was proven useful to time the onset of wake-up stroke; however, identifying the status of FLAIR imaging has been mostly subjective. We aimed to evaluate the value of relative DWI signal intensity (rDWI), and relative apparent diffusion coefficient (rADC) in identifying the FLAIR status in the acute period. Autologous clot was used to embolize left middle cerebral artery in 20 dogs. Magnetic resonance imaging was performed 3-6 hours and 24 hours after embolization. DWI-FLAIR mismatch was defined as hyperintense signal detected on DWI, but not on FLAIR. The mean values of rDWI or rADC of FLAIR- and FLAIR+ lesions were compared and the critical cutoff values of rDWI and rADC for identifying the FLAIR status were determined. Stroke models were successfully established in all animals. DWI+ lesions were found in all 20 dogs from three hours, while FLAIR+ lesions were found in three, 11, 16, 19, and 20 dogs at five time points after embolization, respectively. The mean rDWI values were significantly different between FLAIR- and FLAIR+ lesions (P < 0.001), but rADC values were not (P = 0.73). Using rDWI=1.90 as the threshold value, excellent diagnostic efficacy was achieved (AUC, 0.88; sensitivity, 0.77; specificity, 0.88). However, rADC appeared not useful (AUC, 0.48; sensitivity, 0.52; specificity, 0.58) in identifying the FLAIR status. In our embolic canine stroke model, rDWI was useful to identify FLAIR imaging status in the acute period, while rADC was not.

An 86-year-old woman was admitted following generalized seizure. Postictally she showed disturbance of consciousness, right hemiparesis, and right spatial neglect. Brain fluid attenuated inversion recovery (FLAIR) imaging demonstrated mainly left-sided, but asymmetrical, subcortical white matter lesions. On the second day, level of consciousness improved, along with right hemiparesis and right spatial neglect. Electroencephalography displayed mainly α waves and sporadic θ waves without sharp waves. One week later, however, the patient again experienced somnolence and right hemiparesis. FLAIR revealed day-by-day enlargement of white matter lesions. The possibilities of hypoglycemia, hyperammonemia, hypothyroidism, Hashimoto encephalopathy, collagen disease, antineutrophil cytoplasmic antibody-related angiitis, and infection were excluded based on the results of blood biochemistry and cerebrospinal fluid. We initially suspected intravascular lymphoma, so random skin biopsy was performed, but the results were negative. We then suspected cerebral amyloid angiopathy because of the presence of dementia and multiple microbleeds on T(2)* weighted magnetic resonance imaging. Cerebral biopsy revealed amyloid deposition in cortical arterioles and CD3-positive T cells in the perivascular space. Cerebral amyloid angiopathy-related leukodystrophy was therefore diagnosed and immunosuppressive treatment was started. After 14 days of treatment, clinical symptoms and results of FLAIR imaging were significantly improved. When patients display asymmetrical subcortical white matter lesions with microbleeds on T(2)* weighted imaging, amyloid angiopathy-related inflammation should be considered.

Not Just Blood: Brain Fluid Systems and Their Relevance to Cerebrovascular Diseases.

The automatic segmentation of brain tissues in magnetic resonance (MR) is usually performed on T1-weighted images, due to their high spatial resolution. T1w sequence, however, has some major downsides when brain lesions are present: the altered appearance of diseased tissues causes errors in tissues classification. In order to overcome these drawbacks, we employed two different MR sequences: fluid attenuated inversion recovery (FLAIR) and double inversion recovery (DIR). The former highlights both gray matter (GM) and white matter (WM), the latter highlights GM alone. We propose here a supervised classification scheme that does not require any anatomical a priori information to identify the 3 classes, "GM", "WM", and "background". Features are extracted by means of a local multi-scale texture analysis, computed for each pixel of the DIR and FLAIR sequences. The 9 textures considered are average, standard deviation, kurtosis, entropy, contrast, correlation, energy, homogeneity, and skewness, evaluated on a neighborhood of 3x3, 5x5, and 7x7 pixels. Hence, the total number of features associated to a pixel is 56 (9 textures x3 scales x2 sequences +2 original pixel values). The classifier employed is a Support Vector Machine with Radial Basis Function as kernel. From each of the 4 brain volumes evaluated, a DIR and a FLAIR slice have been selected and manually segmented by 2 expert neurologists, providing 1st and 2nd human reference observations which agree with an average accuracy of 99.03%. SVM performances have been assessed with a 4-fold cross-validation, yielding an average classification accuracy of 98.79%.

In drug-resistant temporal lobe epilepsy (TLE), relative to the large number of whole-brain morphological studies, neocortical T2 changes have not been systematically investigated. The aim of this study was to assess the anatomical principles that govern the distribution of neocortical T2-weighted fluid-attenuated inversion recovery (FLAIR) signal intensity and uncover its topographic principles. Using a surface-based sampling scheme, we mapped neocortical FLAIR intensity of 61 TLE patients relative to 38 healthy controls imaged at 3 T. To address topographic principles of the susceptibility to FLAIR signal changes in TLE, we assessed associations with normative data on tissue composition using 2 complementary approaches. First, we evaluated whether the degree of TLE-related FLAIR intensity changes differed across cytoarchitectonic classes as defined by Von Economo-Koskinas taxonomy. Second, as a proxy to map regions with similar intracortical composition, we carried out a FLAIR intensity covariance paradigm in controls by seeding systematically from all cortical regions, and identified those networks that were the best spatial predictors of the between-group FLAIR changes. Increased intensities were observed in bilateral limbic and paralimbic cortices (hippocampus, parahippocampus, cingulate, temporopolar, insular, orbitofrontal). Effect sizes were highest in periallocortical limbic and insular classes as defined by the Von Economo-Koskinas cytoarchitectonic taxonomy. Furthermore, systematic FLAIR intensity covariance analysis in healthy controls revealed that similarity patterns characteristic of limbic cortices, most notably the hippocampus, served as sensitive predictors for the topography of FLAIR hypersignal in patients. FLAIR intensity findings were robust against correction for morphological confounds. Patients with a history of febrile convulsions showed more marked signal changes in parahippocampal and retrosplenial cortices, known to be strongly connected to the hippocampus. FLAIR intensity mapping and covariance analysis provide a model of TLE gray matter pathology based on shared vulnerability of periallocortical and limbic cortices.

To assess the effects of arginine vasopressin (AVP) on hemodynamic, clinical, and laboratory variables and to determine its adverse side effects in advanced vasodilatory shock. Retrospective study. A total of 316 patients. AVP infusion (4 units/hr). Cardiocirculatory, laboratory, and clinical variables were evaluated before, 0.5, 1, 4, 12, 24, 48, and 72 hrs after administration of AVP. AVP increased mean arterial pressure, systemic vascular resistance, and stroke volume index. Heart rate, central venous pressure, mean pulmonary arterial pressure, norepinephrine, milrinone, and epinephrine requirements decreased. There was no difference in the hemodynamic response between patients with septic shock, postcardiotomy shock, or systemic inflammatory response syndrome. Cardiac index decreased in 41.1% of patients during AVP treatment. In patients with hyperdynamic circulation before AVP, cardiac index decreased, whereas it remained uncharged or tended to increase in patients with normodynamic or hypodynamic circulation. During the course of AVP treatment, liver enzymes (28.5% of patients) and total bilirubin concentrations (69.3% of patients) increased, whereas platelet count decreased (73.4% of patients). Simultaneous hemofiltration significantly contributed to the decrease in platelet count (p < .001) and increase in bilirubin (p < .001). Whereas patients with an increase in bilirubin were more likely to die, a decrease in cardiac index or platelet count and an increase in liver enzymes did not affect mortality. Systemic inflammatory response syndrome as admission diagnosis, a high degree of multiple organ dysfunction, and norepinephrine requirements of >0.5 microg x kg x min before AVP treatment were independent risk factors for death from advanced vasodilatory shock treated with AVP. If norepinephrine dosages exceeded 0.6 microg x kg x min before AVP treatment, a substantial increase in mortality occurred. Supplementary AVP infusion improved cardiocirculatory function in advanced vasodilatory shock, but an increase in liver enzymes and bilirubin, and a decrease in platelet count occurred during AVP therapy, particularly during simultaneous hemofiltration. Initiation of AVP infusion before norepinephrine requirements exceeding 0.6 microg x kg x min may improve outcome.

Background: It is well known that hyperintense vessels (HV) on fluid-attenuated inversion recovery (FLAIR) image suggest slow collateral flow in case of large arterial occlusion. Multiphase CT angiography (CTA) is an imaging technique that provides time-resolved images of pial arteries. We analyzed the correlation of HVs on FLAIR image with collateral vessels on the different phases of multiphase CTA. Methods: FLAIR images and multiphase CTA was analyzed in 7 patients with proximal MCA occlusion. We counted the number of discrete FLAIR HVs distal to the occlusion site and investigated whether the FLAIR HVs could be seen at the same area in different phases of multiphase CTA. Results: The mean duration between symptom onset and acquisition of multiphase CTA was 5.6 hours and mean duration between CTA and MRI was 0.6 hour. A total 32 FLAIR HVs were observed in 7 patients. Of these, 13 HVs were observed in the 1 st phase CTA, 25 HVs in the 2 nd phase, and 26 HVs in the 3 rd phase. Six HVs were not observed in all three phases of CTA. Conclusions: In cases of acute proximal MCA occlusion, the collateral vessels shown as FLAIR HVs are more frequently observed in the late phase of multiphase CTA. Fig 1. A 74-year-old man with acute occlusion of left middle cerebral artery. FLAIR image (A) shows 3 discrete HVs at left temporoparietal area. These FLAIR HVs are most clearly seen at 3 rd phase contrast enhanced CTA (D) B, C: 1 st and 2 nd phase contrast enhanced CTA