Is There Extra Cost of Institutional Care for MS Patients?

Throughout life, patients with multiple sclerosis (MS) require increasing levels of support, rehabilitative services, and eventual skilled nursing facility (SNF) care. There are concerns that access to SNF care for MS patients is limited because of perceived higher costs of their care. This study compares costs of caring for an MS patient versus those of a typical SNF patient. We merged SNF cost report data with the 2001-2006 Nursing Home Minimum Data Set (MDS) to calculate percentage of MS residents-days and facility case-mix indices (CMIs). We estimated the average facility daily cost using hybrid cost functions, adjusted for facility ownership, average facility wages, CMI-adjusted number of SNF days, and percentage of MS residents-days. We describe specific characteristics of SNF with high and low MS volumes and examine any sources of variation in cost. MS patients were no longer more costly than typical SNF patients. A greater proportion of MS patients had no significant effect on facility daily costs (P = 0.26). MS patients were more likely to receive care in government-owned facilities (OR = 1.904) located in the Western (OR = 2.133) and Midwestern (OR = 1.3) parts of the USA (P < 0.05). Cost of SNF care is not a likely explanation for the perceived access barriers that MS patients face

Natalizumab in pediatric multiple sclerosis patients

Abstract: Pediatric multiple sclerosis (MS) comprises 25% of all cases of MS. Although first-line disease-modifying therapy (DMT) including interferons and glatiramer acetate appear to be well tolerated in this population, recent work has suggested that a growing number of children suffer from disease which is resistant to treatment with these therapies. Natalizumab is a therapy which, although associated with a 1 : 1000 risk for progressive multifocal leukoencephalopathy (PML), has been shown to be well tolerated in the adult population and may lead to disease remission in adults with highly active disease. Reports of use of this therapy in the pediatric population with highly active disease have been published. This paper reviews current experience with the use of natalizumab in the pediatric MS population, with attention to potential risks and possible long-term outcomes in this population

Ontologies for the study of neurological disease

We have begun work on two separate but related ontologies for the study of neurological diseases. The first, the Neurological Disease Ontology (ND), is intended to provide a set of controlled, logically connected classes to describe the range of neurological diseases and their associated signs and symptoms, assessments, diagnoses, and interventions that are encountered in the course of clinical practice. ND is built as an extension of the Ontology for General Medical Sciences — a high-level candidate OBO Foundry ontology that provides a set of general classes that can be used to describe general aspects of medical science. ND is being built with classes utilizing both textual and axiomatized definitions that describe and formalize the relations between instances of other classes within the ontology itself as well as to external ontologies such as the Gene Ontology, Cell Ontology, Protein Ontology, and Chemical Entities of Biological Interest. In addition, references to similar or associated terms in external ontologies, vocabularies and terminologies are included when possible. Initial work on ND is focused on the areas of Alzheimer’s and other diseases associated with dementia, multiple sclerosis, and stroke and cerebrovascular disease. Extensions to additional groups of neurological diseases are planned. The second ontology, the Neuro-Psychological Testing Ontology (NPT), is intended to provide a set of classes for the annotation of neuropsychological testing data. The intention of this ontology is to allow for the integration of results from a variety of neuropsychological tests that assay similar measures of cognitive functioning. Neuro-psychological testing is an important component in developing the clinical picture used in the diagnosis of patients with a range of neurological diseases, such as Alzheimer’s disease and multiple sclerosis, and following stroke or traumatic brain injury. NPT is being developed as an extension to the Ontology for Biomedical Investigations

Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubation with the flavonoid luteolin: additive effects of IFN-β

The study is aimed to determine the role of luteolin (3',4',5,7-tetrahydroxyflavone), alone and in combination with human interferon-beta (IFN-β), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMCs) isolated from multiple sclerosis (MS) patients. PBMC proliferation in the presence or absence of these drugs was determined and the production of pro-inflammatory cytokines (IL-1β, TNF-α), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 was assessed in the culture supernatants. Luteolin reduced, in a dose-dependent manner, the proliferation of PBMCs, and modulated the levels of IL-1β and TNF-α released by PBMCs in the culture supernatants. Luteolin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. In the majority of cases, luteolin, when combined with IFN-β, had additive effects in modulating cell proliferation, IL-1β, TNF-α, MMP-9 and TIMP-1

The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging

Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus (EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention

Crosstalk between hemostasis inhibitors and cholesterol biomarkers in multiple sclerosis

The individual roles of cholesterol pathway biomarkers (CPB) and hemostasis inhibitors with neuroimaging outcomes were previously investigated in multiple sclerosis (MS). The purpose of this extension study was to investigate potential crosstalk between plasma CPB [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoproteins (Apo) ApoA-I, ApoAII, ApoB, ApoC-II and ApoE] and hemostasis inhibitors [heparin cofactor-II (HCII), protein C (PC), protein S (PS), thrombomodulin, ADAMTS13 and PAI-1] in a cohort of 127 MS patients, and 40 healthy individuals (HI). The associations were assessed with regressions. In MS patients, HCII was positively associated with TC, LDL-C, HDL-C and ApoA-I (p=0.028, 0.027, 0.002 and 0.027, respectively) but negatively associated with ApoCII (p=0.018). PC was positively associated with ApoC-II (p=0.001) and ApoB (p=0.016) whereas PS was associated with TC (p=0.024) and ApoE (p=0.003) in MS. The ApoC-II associations were not observed in HI. The negative association between ApoC-II and HCll was an exception amongst other positive associations between CPB and hemostasis inhibitors in MS. CPB do not modulate the PC associations with neurodegeneration in MS

Retinal blood vessel analysis using optical coherence tomography in multiple sclerosis

Background: Both greater retinal neurodegenerative pathology and greater cardiovascular burden have been seen in persons with multiple sclerosis (pwMS).1,2 Moreover, studies have described multiple extracranial and intracranial vasculature changes in pwMS.3 However, only a few studies have examined the retinal vasculature in multiple sclerosis (MS). Objectives: To determine if there are differences in retinal vasculature between pwMS and healthy controls (HCs) and their relationship to peripapillary retinal nerve fiber layer (pRNFL) thickness. Materials and methods: A total of 167 pwMS (113 relapsing-remitting MS (RRMS) and 54 progressive MS (PMS)) and 48 HCs were scanned using optical coherence tomography (OCT). Earlier OCT scans were available in a smaller sample size of 101 pwMS and 35 HCs for additional longitudinal 5-year follow-up analysis. The semiautomated segmentation of the retinal vasculature was performed in a blinded manner on peripapillary scans using the optical coherence tomography segmentation and evaluation GUI (OCTSEG) in MatLab. (Figure 1). Automated segmentation of the pRNFL was performed in the native Heidelberg OCT software. The sum of bilateral measures of total retinal vessel diameter, the total number of retinal vessels and average vessel diameter were calculated. Independent sample t-test and paired t-test were used for cross-sectional and longitudinal analyses, respectively and non-parametric Spearman's test for determining correlations. Results: PwMS had a significantly smaller total vessel diameter (2.5 cm vs 2.7 cm, age-adjusted p=0.017) and numerically fewer number of retinal vessels when compared to HCs (35.1 vs 36.8, age-adjusted p=0.167). No significant differences between the pwRRMS and pwPMS were found. Over the follow-up, pwMS had significant decrease in number of retinal vessels (36.7 vs. 33.0, p<0.001) and significant increase in the average vessel diameter (0.072cm vs. 0.081cm, p<0.001). No longitudinal changes in the HCs were noted. Only in pwMS, lower pRNFL was associated with fewer retinal vessels and total vessel diameter (r=0.191, p=0.018 and r=0.216, p=0.007). Conclusions: PwMS have retinal vasculature that results in smaller and fewer retinal vessels when compared to HCs that were related to reduced pRNFL. Over time, a reduction of retinal vasculature occurred. Future investigations should determine the relevance of retinal vasculature in regards to MS disease outcomes, presence of cardiovascular abnormalities and cerebral/retinal perfusion

Associations between changes in ferritin levels and susceptibility-weighted imaging filtered phase in patients with relapsing–remitting multiple sclerosis over 24weeks of therapy with subcutaneous interferon beta-1a three times weekly

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Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report

<p>Abstract</p> <p>Background</p> <p>Several studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI).</p> <p>Methods</p> <p>We investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities.</p> <p>Results</p> <p>There was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (<it>r </it>= -0.70 to -0.71, <it>P </it>< 0.002 and <it>P </it>corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (<it>r </it>= -0.59 to -0.71, <it>P </it>< 0.01 and <it>P </it>corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction.</p> <p>Conclusions</p> <p>This pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.</p

Plasma 24-hydroxycholesterol is associated with narrower common carotid artery and greater flow velocities in relapsing multiple sclerosis

Background: Multiple sclerosis (MS) studies suggest greater cardiovascular disease burden and disturbances in the cholesterol pathways1,2 The potential impact of oxidized cholesterol molecules (oxysterols) on MS is emerging (Figure 1).3 Objective: To determine the relationship between multiple oxysterol molecules and atherosclerosis burden in MS patients. Materials and methods: A total of 99 MS patients (61 relapsing-remitting MS (RRMS) and 38 progressive MS (PMS)) patients and 38 healthy controls (HCs) underwent magnetic resonance angiography (MRA) and the cross-sectional area (CSA) of the common carotid artery (CCA) was determined at three different levels before the bifurcation (C7, C6 and C5). Additionally, an echo-color Doppler ultrasound was performed and measures of blood flow velocities were derived. Blood samples acquired at the time of the imaging examinations were analyzed and 24-, 25-, 27-hydroxycholesterol (24HC, 25HC, 27HC) and 7-ketocholesterol (7KC) were quantified in ng/mL. Results: In the MS patients, higher levels of 24HC were significantly associated with smaller CCA CSA measured at all three cervical levels (r=-0.201, p=0.046; r=-0.228, p=0.023, and r=-0.215, p=0.032, for C7, C6 and C5, respectively). These associations were driven by the RRMS group only (r=-0.407, p=0.002 for C7; r=-0.414, p=0.002, for C6; and r=-0.368, p=0.006 for C5). No associations were seen in the HCs. Despite adjusting for the significant age effect (B=0.445, p=0.004), higher 24HC levels were independently associated with smaller CCA CSA (B=-0.20, p=0.045). 24HC was additionally associated with greater time-averaged and peak diastolic CCA velocities. RRMS patients treated with potent anti-inflammatory therapies had lower oxysterol levels (p=0.019). RRMS patients in the lower 24HC quartiles had significantly higher expanded disability status scale (EDSS) scores when compared to RRMS patients in the higher two 24HC quartiles (2.5 (IQR 1.9-3.1) vs 2.0 (1.5-2.5), p=0.038). Conclusions: Greater 24HC levels are associated with smaller CSA CCA and greater flow velocities in RRMS patients. The higher inflammatory activity in RRMS patients may contribute to the production of highly reactive oxysterols and worsen the atherosclerotic burden in the MS population. Potent anti-inflammatory medications can significantly decrease oxysterol levels