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No description available.

No description available.

We aimed to assess whether frontal cortex-striatum-thalamus (FCST) pathway or other grey matter (GM) structures are associated with longitudinal patterns of fatigue, namely reversible (RF) versus sustained fatigue (SF). MS patients enrolled in our prospective cohort were grouped based on their longitudinal Modified Fatigue Impact Scale (MFIS) scores: 1. SF: MFIS≥38 at the two most recent yearly assessments; 2. RF: MFIS<38 at last assessment, but presence of at least one previous MFIS≥38; 3. Never Fatigued (NF): at least five MFIS<38. Accordingly, we selected 98 patients (30 SF, 31 RF, 37 NF; age-range:29-66, female/male:76/22, Extended Disability Status Scale (EDSS)6; 13 patients with secondary progressive (SP) MS and 85 with relapsing remitting (RR) MS in remission). Disability and depression were assessed using the EDSS and CES-D, respectively. 3T T1-weighted MRI was used for voxel based morphometry (VBM) to survey for GM atrophy associated with fatigue, controlling for age, sex and EDSS. Group-wise volumetric comparison was performed on deep GM structures identified by VBM, controlling for age, sex, EDSS and CES-D score. VBM showed significant inverse relation between the MFIS cognitive subscale score and areas within the bilateral fronto-medial and fronto-orbital cortices, anterior striata, thalami, temporal poles, insulae and left lateral occipital cortex (peak FWE-p value of 0.021), and between the MFIS physical subscale and areas within the bilateral frontal poles, and frontal medial cortices (peak FWE-p value of 0.043). Volumetric analysis showed significant atrophy in the putamen (RF<NF p<0.0004; SF<NF p<0.0085) and thalamus (RF<NF p<0.00048).

abstract: Multiple Sclerosis, an autoimmune disease, is one of the most common neurological disorder in which demyelinating of the axon occurs. The main symptoms of MS disease are fatigue, vision problems, stability issue, balance problems. Unfortunately, currently available treatments for this disease do not always guarantee the improvement of the condition of the MS patient and there has not been an accurate mechanism to measure the effectiveness of the treatment due to inter-patient heterogeneity. The factors that count for varying the performance of MS patients include environmental setting, weather, psychological status, dressing style and more. Also, patients may react differently while examined at specially arranged setting and this may not be the same while he/she is at home. Hence, it becomes a major problem for MS patients that how effectively a treatment slows down the progress of the disease and gives a relief for the patient. This thesis is trying to build a reliable system to estimate how good a treatment is for MS patients. Here I study the kinematic variables such as velocity of walking, stride length, variability and so on to find and compare the variations of the patient after a treatment given by the doctor, and trace these parameters for some patients after the treatment effect subdued. / Dissertation/Thesis / M.S. Bioengineering 2012

There is no single test clinically available that is independently diagnostic for multiple sclerosis (MS). Currently MS is diagnosed using a combination of clinical evaluation and investigations including magnetic resonance imaging (MRI), interpreted in accordance with diagnostic criteria, to demonstrate the requisite dissemination of lesions in (anatomical) space and time. Lesions comprising inflammatory demyelination in the central nervous system are a core pathological feature of MS. Ultra-high field (e.g. 7 Tesla or 7T) T2*-weighted MRI can demonstrate in vivo a central vein in most of these lesions. This is a histopathologically specific feature which could be exploited to improve diagnostic workup in cases of suspected inflammatory demyelination. Central nervous system white matter not involved in demyelinating lesions is nevertheless affected in MS. The mechanisms inflicting injury to this normal appearing white matter (NAWM) and how they relate to focal lesions are unclear. Damage to NAWM seems important, because it correlates well with disability. Any association between cortical lesions, focal white matter lesions (WML) and diffuse damage to NAWM is difficult to investigate in vivo in MS, principally because MRI is relatively insensitive to cortical lesions. Investigation of such associations may also be confounded by the presence of small focal lesions within the “NAWM” that may remain undetected when using conventional MRI to define NAWM. Advantages inherent to ultra-high field MRI might help mitigate both of these problems.

Background: The 18 kDa translocator protein (TSPO), expressed at a low level in the healthy human central nervous system (CNS), is upregulated in inflammatory brain diseases by activated microglia and other immune cells. Using positron emission tomography (PET) radioligands targeting TSPO, it is possible to localise this signal and map the course of microglial activation and its effects on disease progression. Here, a newly developed second generation TSPO PET ligand, [18F]GE-180, was evaluated in different models of preclinical and clinical neuroinflammatory disease. Methods: A preclinical model of low-level inflammation with lipopolysaccharide (LPS) was designed. Rats were scanned with the first generation TSPO ligand [11C]- (R)-PK11195 and either [18F]GE-180 or [18F]DPA-714, with dual scanning enabling the direct comparison of second generation tracers with [11C]-(R)-PK11195. An arterial blood sampling system for rodent imaging with [18F]DPA-714 was set up and characterised. The performance of [18F]GE-180 was assessed in a clinical study in nine relapsing-remitting multiple sclerosis patients (RRMS) and ten healthy volunteers (HV). A comparison of kinetic modelling approaches for [18F]GE-180 human brain PET data was performed, as well as a longitudinal analysis with intervention using the disease-modifying treatment, natalizumab to evaluate the potential of [18F]GE-180 as a biomarker for therapy monitoring in MS subjects. Finally, the plasma-protein binding behaviour of [18F]GE-180 was evaluated in vitro using ultrafiltration. Results: In LPS animals, [18F]GE-180 produced a significantly higher ipsi- to contralateral uptake ratio and binding potential () than [11C]-(R)-PK11195 (p = 0.03), but [18F]DPA-714 did not. There was no significant difference between animals scanned with [18F]GE-180 and [18F]DPA-714, suggesting no overall superiority of the former. Characterisation of an arterial sampling system for rodent studies with [18F]DPA-714 allowed correction for dispersion effects. A comparison of reference regions showed that a novel externally derived tissue estimated with lower bias than a contralateral reference region. In human [18F]GE-180 brain PET data, the unconstrained two-tissue compartment model (2TCM) best described tracer behaviour in RRMS and HV subjects. Normal appearing white matter (NAWM) in patients was elevated over that of HVs. Standardised uptake values (SUVs) for the tracer in rodents were 0.28±0.12 and 0.84±0.31 in healthy tissue and LPS lesions respectively, and in humans were 0.36±0.04 (HV) and 0.58 (in a gadolinium- enhancing MS lesion). [18F]GE-180 uptake was also significantly reduced in the brains of RRMS subjects treated with natalizumab, correlating with clinically-identified improvement. [18F]GE-180 has a free fraction of between 1 and 8%.Conclusions: [18F]GE-180 shows good brain uptake in the rodent brain and produces superior signal to [11C]-(R)-PK11195, but not to [18F]DPA-714. The 2TCM fits human [18F]GE-180 PET data well, and the tracer is able to identify an elevated signal in RRMS patients compared to healthy subjects. [18F]GE-180 shows a large fraction of non-displaceable binding in human blood, thus further optimisation of kinetic modelling approaches is suggested.

This work is to them who have recently received the diagnosed with Multiple Sclerosis (MS), since the disease is quite a life changer this by creating limitations and cause serious health problems. Problems that would changes their life forever, this in adapting to their new life situation where communication has become harder this to express in an understandable way and understanding has become even harder. Since being diagnosed with MS it affect more than a single person, the one diagnosed family is also experiencing almost the same sort of difficulties and life changer. In not knowing what their family member is trying to express, this in order to make the family understand them will create a gap between them of misunderstanding. Evan the healthcare experience this sort of troubles when they are trying to understand what their patient is trying to express, without the proper understanding it might cause mistreatment of the patient. With a clearer understanding of their patient could they early understand their patients in knowing what they are trying to express. Since the healthcare staffs has been educated about this sort of disease would an easy understanding about their patient be helpful, this to provide the patient with the proper care. People that has never heard and been in contact with this sort of disease and what sort of features it could cause would be enlighten about the disease as well how it is to live with it. Providing an eye-opener to the public in what this disease is and what sort of problems it causes, this to inform and sharing the information. By sharing the information concerning this would the public be enlighten and have an understanding about the problems, which the person with MS experience. In order of enable, this sort of understanding between those with MS and the healthy ones would to use design in order of creating a sort of platform of common understanding. Creating a sort of bridge of understanding between healthy people and those with MS, it would improve the understanding of the person with MS as well the disease itself. This sort of tool would be helpful in the health care in helping those who recently been diagnosed with MS, reducing the stress in knowing their disease. This would as well ease and milder the shock of them diagnosed, providing them some sort of comfort in knowing their disease. To understand this sort of problems and symptoms, it would be possible to enlighten people as well health care, about the hardship that those who live with MS which they are enduring each day. To be diagnosed with MS and not knowing about what it is could cause extreme stress, worsening the diseases, being in a new situation with an unknown disease, without having someone to ask about this, expect the healthcare. In healthcare there exists no book written by one having MS describing the different symptoms as well the troubles, which they experience, this sort of information would be helpful since the one having MS wants to know from one experience the same troubles as they. To feel the comfort regarding their disease as well to feel that there is someone that has gone through the same experience as they have gone through. The result, which is a book that would act as a tool for understanding the disease, its troubles and problems in a clear as well informed way. This would create a sort of bridge of understanding between those with MS and those without. The pictures in the book are illustrating and informing in a clear way about the disease and its different symptoms. Since the disease is difficult to understand due to its diversity of problems, the book is displaying some of the most common problems in how it is to experience MS. This sort of book could help the already diagnosed in understanding their disease and be something they could find comfort to know as well knowing that someone else has experienced the same things as them.

Thesis (MTech (BioMedical Technology))--Cape Peninsula University of Technology, 2006 / In multiple sclerosis (MS) the myelin sheaths surrounding the axons in the brain are mainly affected by the disease process. Myelin consists for the most part of lipids and proteins. An abnormality in essential fatty acid metabolism is known to be present in patients with MS (Horrobin, 1979), reflected in a high ratio of n-6 to n-3 fatty acids in cell membranes. It has also been established previously that the pathogenesis of inflammatory disorders is aggravated by excessive consumption of n-6 fatty acids relative to n-3 fatty acids (Guesnet et al., 2005),and it has been shown that ingesting a larger proportion of n-3 fatty acids could be crucial in the regulation of cellular physiology and in the prevention of pathologies such as autoimmune and inflammatory diseases. Modern Western medical treatment for autoimmune diseases, which includes MS, involves the administration of immunosuppressive drugs, such as beta interferon, cortisone (prednisone), methotrexate and cytoxan, which reduce the effectiveness of the entire Immune system, and can have serious, sometimes life threatening, side effec1s (Perlmutter, 2006, htlp:/Iwww.msfac1s.org). It would therefore be of interest to investigate other options for treatment Although there is an extensive literature on fatly acids in MS, the actual details of the mechanisms of fatly add imbalances in MS have not been established. It would therefore be advisable to Investigate the abnormality of the MS cell membrane fatly acid profile. Previous studies focused on individual fatty acids, but it would be more relevant to investigate the relationships within and between the n-6 and n-3 series, and their effect on outcome, and to establish any possible cumulative effects, because the metabolism of fatty adds within the two series does have an effect on one another.