dirty appearing white matter a disregarded entity in multiple sclerosis

In patients with multiple sclerosis (MS), the term dirty-appearing white matter (DAWM) refers to brain regions of intermediate signal intensity between those of focal lesions and normal-appearing white matter (NAWM) on T2-weighted and proton attenuation–weighted images.[1][1][][2][][3]–[4][4

mr imaging of gray matter involvement in multiple sclerosis implications for understanding disease pathophysiology and monitoring treatment efficacy

SUMMARY: Recent pathologic and MR imaging studies have challenged the classic view of MS as a chronic inflammatory-demyelinating condition affecting solely the WM of the central nervous system. Indeed, an involvement of the GM has been shown to occur from the early stages of the disease, to progress with time, and to be only moderately correlated with the extent of WM injury. In this review, we summarize how advances in MR imaging technology and methods of analysis are contributing to ameliorating the detection of focal lesions and to quantifying the extent of "occult" pathology and atrophy, as well as to defining the topographic distribution of such changes in the GM of patients with MS. These advances, combined with the imaging of brain reorganization occurring after tissue injury, should ultimately result in an improved understanding and monitoring of MS clinical manifestations and evolution, either natural or modified by treatment. Cereb : cerebellum Cho : choline CIS : clinically isolated syndromes DIR : double inversion recovery DTI : diffusion tensor imaging EDSS : Expanded Disability Status Scale FA : fractional anisotropy FLAIR : fluid-attenuated inversion recovery fMRI : functional MR imaging GM : gray matter L : left MD : mean diffusivity MS : multiple sclerosis MT : magnetization transfer MTR : magnetization transfer ratio NAA : N -acetylaspartate NAWM : normal-appearing white matter PM : premotor cortex PPMS : primary-progressive MS R : right RRMS : relapsing-remitting MS RT : relaxation time SII : secondary sensorimotor cortex SMA : supplementary motor area SMC : sensorimotor cortex SPM : statistical parametric mapping SPMS : secondary-progressive MS Thal : thalamus WM : white matte

dentate nucleus t1 hyperintensity in multiple sclerosis

Gray matter (GM) damage, in terms of focal lesions,[1][1] "diffuse" tissue injury, and atrophy is a well-known feature of multiple sclerosis (MS). Recently, T1-hyperintensity on unenhanced T1-weighted sequences has been found in the dentate nuclei of patients with MS with severe disability an

spatial normalization and regional assessment of cord atrophy voxel based analysis of cervical cord 3d t1 weighted images

BACKGROUND AND PURPOSE: VBM is widely applied to characterize regional differences in brain volume among groups of subjects. The aim of this study was to develop and validate a method for voxelwise statistical analysis of cord volume and to test, with this method, the correlation between cord tissue loss and aging. MATERIALS AND METHODS: 3D T1-weighted scans of the spinal cord were acquired from 90 healthy subjects spanning several decades of life. Using an AS method, we outlined the cord surface and created output images reformatted with image planes perpendicular to the estimated cord centerline. Unfolded cervical cord images were coregistered into a common standard space, and smoothed cord binary masks, produced by using the cord outlines estimated by the AS approach, were used as input images for spatial statistics. RESULTS: High spatial correlation between normalized images was observed. Averaging of the normalized scans allowed the creation of a cervical cord template and of a standardized region-of-interest atlas. VBM analysis showed some significant associations between a decreased probability of cord tissue and aging. Results were robust across different smoothing levels, but the use of an anisotropic Gaussian kernel gave the optimal trade-off between spatial resolution and the requirements of the Gaussian random field theory. CONCLUSIONS: VBM analysis of the cervical cord was feasible and holds great promise for accurate localization of regional cord atrophy in several neurologic conditions

thalamic damage predicts the evolution of primary progressive multiple sclerosis at 5 years

BACKGROUND AND PURPOSE: Reliable markers to monitor PPMS are still needed. We investigated whether conventional and DTI measures of thalamic damage are predictive of long-term disability accumulation in PPMS. MATERIALS AND METHODS: Brain conventional and DTI scans were obtained at baseline and after a mean follow-up of 15 months in 54 patients with PPMS and 8 healthy controls. Patients were reassessed clinically after 5 years. At baseline and follow-up, measures of lesion load, brain atrophy, and NTV were obtained. MD and FA histograms of the NAWM, the whole GM without the thalami, and the thalami were obtained. A multivariate analysis evaluated the predictors of long-term neurologic deterioration. RESULTS: At follow-up, 35 patients showed disability worsening. At baseline, compared with healthy controls, patients with PPMS had lower NTV ( P P = .002) and higher thalamic ( P = .002) and whole GM without the thalami ( P = .005) MD. During follow-up, the change of thalamic FA was higher in PPMS versus healthy controls ( P = .01). Baseline NTV and thalamic DTI quantities differed significantly between patients with PPMS with and without thalamic lesions. Baseline thalamic quantities were significantly correlated with the extent of brain T2 lesions and the severity of NAWM damage. The multivariate model included average NAWM MD (OR = 1.46, P = .005) and FA thalamic change (OR = 0.84, P = .02) as independent predictors of EDSS score deterioration (Nagelkerke R 2 = 0.55). CONCLUSIONS: Short-term accrual of thalamic damage and the severity of NAWM involvement predict the long-term accumulation of disability in PPMS

Functional MR Imaging Correlates of Neuropsychological Impairment in Primary-Progressive Multiple Sclerosis

BACKGROUND AND PURPOSE: Cognitive deficits affect ≤30% of patients with PPMS. We investigated the functional correlates of cognitive network dysfunction in patients with PPMS and their correlation with the extent of structural MR imaging damage. MATERIALS AND METHODS: From 16 right-handed patients with PPMS and 17 matched controls, structural and fMRIs (during the performance of the 2-back task) were acquired. Neuropsychological tests exploring memory, attention, and frontal lobe cognitive domains were administered. T2 LL, NBV, and CC areas were measured. RESULTS: Six patients with PPMS were CI. Structural MR imaging measures did not differ between patients who were CI and those who were CP. Compared with patients who were CI, patients who were CP had increased activations of the left caudate nucleus, PFC, and inferior parietal lobule. Compared with controls and patients who were CP, patients who were CI had increased activations of the SII, cerebellum, and insula. Compared with controls, they also had increased activations of the right precentral gyrus and a reduced recruitment of the left PFC. In patients with PPMS, a decreased composite cognitive score correlated with increased activity of the cerebellum, insula, and SII, as well as decreased PFC activity. T2 LL correlated with decreased PFC recruitment and increased SII recruitment. CONCLUSIONS: In PPMS, an increased recruitment of cognitive-related networks might represent a functional reserve with the potential to limit the severity of cognitive impairment. The accumulation of T2 lesions and the consequent exhaustion of frontal lobe plasticity might contribute to cognitive impairment in PPMS

A three-year study of brain atrophy after autologous hematopoietic stem cell transplantation in rapidly evolving secondary progressive multiple sclerosis

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), autologous hematopoietic stem cell transplantation (AHSCT) induces a profound suppression of clinical activity and MR imaging-detectable inflammation, but it may be associated with a rapid brain volume loss in the months subsequent to treatment. The aim of this study was to assess how AHSCT affects medium-term evolution of brain atrophy in MS. MATERIALS AND METHODS: MR imaging scans of the brain from 14 patients with rapidly evolving secondary-progressive MS obtained 3 months before and every year after AHSCT for 3 years were analyzed. Baseline normalized brain volumes and longitudinal percentage of brain volume changes (PBVCs) were assessed using the Structural Image Evaluation of Normalized Atrophy software. RESULTS: The median decrease of brain volume was 1.92% over the first year after AHSCT and then declined to 1.35% at the second year and to 0.69% at the third year. The number of enhancing lesions seen on the pretreatment scans was significantly correlated with the PBVCs between baseline and month 12 (r = -0.62; P = .02); no correlation was found with the PBVCs measured over the second and third years. CONCLUSIONS: After AHSCT, the rate of brain tissue loss in patients with MS declines dramatically after the first 2 years. The initial rapid development of brain atrophy may be a late consequence of the pretransplant disease activity and/or a transient result of the intense immunoablative conditioning procedure

Toward multitasking pharmacological COX-targeting agents: Non-steroidal anti-inflammatory prodrugs with antiproliferative effects

The antitumor activity of certain anti-inflammatory drugs is often attributed to an indirect effect based on the inhibition of COX enzymes. In the case of anti-inflammatory prodrugs, this property could be attributed to the parent molecules with mechanism other than COX inhibition, particularly through formulations capable of slowing down their metabolic conversion. In this work, a pilot docking study aimed at comparing the interaction of two prodrugs, nabumetone (NB) and its tricyclic analog 7-methoxy-2, 3-dihydro-1H-cyclopenta[b]naphthalen-1-one (MC), and their common active metabolite 6-methoxy-2-naphthylacetic acid (MNA) with the COX binding site, was carried out. Cytotoxicity, cytofluorimetry, and protein expression assays on prodrugs were also performed to assess their potential as antiproliferative agents that could help hypothesize an effective use as anticancer therapeutics. Encouraging results suggest that the studied compounds could act not only as precursors of the anti-inflammatory metabolite, but also as direct antiproliferative agents. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A Semiautomatic Method for Multiple Sclerosis Lesion Segmentation on Dual-Echo MR Imaging: Application in a Multicenter Context

BACKGROUND AND PURPOSE: The automatic segmentation of MS lesions could reduce time required for image processing together with inter- and intraoperator variability for research and clinical trials. A multicenter validation of a proposed semiautomatic method for hyperintense MS lesion segmentation on dual-echo MR imaging is presented. MATERIALS AND METHODS: The classification technique used is based on a region-growing approach starting from manual lesion identification by an expert observer with a final segmentation-refinement step. The method was validated in a cohort of 52 patients with relapsing-remitting MS, with dual-echo images acquired in 6 different European centers. RESULTS: We found a mathematic expression that made the optimization of the method independent of the need for a training dataset. The automatic segmentation was in good agreement with the manual segmentation (dice similarity coefficient = 0.62 and root mean square error = 2 mL). Assessment of the segmentation errors showed no significant differences in algorithm performance between the different MR scanner manufacturers (P > .05). CONCLUSIONS: The method proved to be robust, and no center-specific training of the algorithm was required, offering the possibility for application in a clinical setting. Adoption of the method should lead to improved reliability and less operator time required for image analysis in research and clinical trials in MS

Vinorelbine-based chemotherapy in hormone refractory prostate cancer

Background: No consensus exists regarding further therapy for the management of hormone-refractory prostate cancer. In this phase II study, the combination of Vinorelbine with 5-Fluorouracil and folinic acid (FLN regimen) was evaluated in patients with progressive or resistant disease after hormone therapy. Patients and Methods: Thirty-four patients were treated with Vinorelbine at a dose of 20 mg/m 2 intravenously (i.v.) on days 1 and 3, folinic acid (FA), 100 mg/m 2 i.v. and 5-Fluorouracil (5-FU), 350 mg/m 2 i.v. as a short infusion on days 1 to 3. The therapy was given in an out-patient setting, every 3 weeks. Results: All of the 34 eligible patients were evaluable for toxicity and 30 for activity. A total of 127 cycles was administered (91% at full dose). Among the 15 patients with measurable disease, four had a partial response (26.6%; C.I. 95%, 28.3% to 65.7%) and four achieved stable disease. In 14 patients (47%) a clinical benefit was documented. Six out of 15 patients with bone-only involvement had stable disease (40%). The median duration of stabilization and partial response was 16 weeks (range 4-24 weeks). The most common toxicity was hematological: Grade 4 (NCI-CTC scale) in five patients at re-cycle. Other toxicities were of low incidence and easy to manage. Conclusion: The encouraging results obtained with the FLN regimen in terms of clinical benefit and its predictable and manageable toxicity support the palliative role of this chemotherapeutic strategy in hormone-refractory prostate patients