Magnetic Resonance Imaging Predictors for Disability in Multiple Sclerosis

Castelijns, J.A. [Promotor]Barkhof, F. [Promotor]Polman, C.H. [Promotor]Uitdehaag, B.M.J. [Copromotor

Predicting short-term disability progression in early multiple sclerosis: Added value of MRI parameters

Objective: Magnetic resonance imaging (MRI) and clinical parameters are associated with disease progression in multiple sclerosis (MS). The aim of this study was to investigate whether adding MRI parameters to a model with only clinical parameters could improve these associations. Methods: 89 patients (55 women) with recently diagnosed MS had clinical and MRI evaluation at baseline (time of diagnosis) and at follow-up after 2.2 years. Detailed clinical data were available, including disease type (relapse-onset or progressive-onset) and disability, as measured by the Expanded Disability Status Scale (EDSS). MRI parameters included Normalised Brain Volume (NBV) at baseline, percentage brain volume change (PBVC/year), T2- and T1-lesion loads and spinal cord abnormalities. Progression of disability (increase in EDSS of at least 1 point at follow-up) was the main outcome measure. For a model containing only clinical parameters, the added value of MRI parameters was tested using logistic regression. Results: PBVC/year and lesion loads at follow-up were significantly higher in the group with progression. Adding PBVC/year to a clinical model improved the model, indicating that MRI parameters added independent information (p<0.001). Conclusion: The rate of cerebral atrophy conveys added information for the progression of disability in patients with early MS, suggesting that clinical disability is determined by neurodegenerative changes as depicted by MRI

Vitality, perceived social support and disease activity determine the performance of social roles in recently diagnosed multiple sclerosis: a longitudinal analysis.

Objective: The aim of this study was to identify the principal determinants that are longitudinally associated with the performance of social roles in the first 3 years following a diagnosis of multiple sclerosis. Design: Inception cohort with 5 measurements over 3 years. Patients: A total of 156 patients recently diagnosed with multiple sclerosis. Method: Performance of social roles was measured using the 2 role functioning and the social sub-scales of the Medical Outcome Study Short Form 36. Potential determinants (n = 43) were divided into the following clusters: patient and disease characteristics (n = 12), psychosocial characteristics (n= 10), basic functions (n= 18) and basic activities (n= 3). Multivariate longitudinal regression analyses were performed with generalized estimating equations. A backwards selection procedure for every cluster per outcome reduced the large number of potential determinants. In order to determine whether longitudinal associations are present the selected determinants were entered into an overall regression model. Results: Twenty-three candidate determinants were selected. Vitality, measured with the SF36 sub-scale vitality, the T2-weighted supratentorial lesion load and the perceived amount of social support, measured with the Social Support List Discrepancies, were longitudinally associated with the performance of social roles in 2 or 3 of the models. Conclusion: Vitality, the perceived amount of social support, and disease activity, i.e. the T2-weighted supratentorial lesion load, determine the performance of social roles in the early stages of multiple sclerosis. © 2007 The Authors. Journal Compilation © 2007 Foundation of Rehabilitation Information

The influence of partners on successful lifestyle modification in patients with coronary artery disease

Background: Marital status is associated with prognosis in patients with cardiovascular disease (CVD). However, the influence of partners on successful modification of lifestyle-related risk factors (LRFs) in secondary CVD prevention is unclear. Therefore, we studied the association between the presence of a partner, partner participation in lifestyle interventions and LRF modification in patients with coronary artery disease (CAD). Methods: In a secondary analysis of the RESPONSE-2 trial (n = 711), which compared nurse-coordinated referral to community-based lifestyle programs (smoking cessation, weight reduction and/or physical activity) to usual care in patients with CAD, we investigated the association between the presence of a partner and the level of partner participation on improvement in >1 LRF (urinary cotinine <200 ng/l, ≥5% weight reduction, ≥10% increased 6-min walking distance) without deterioration in other LRFs at 12 months follow-up. Results: The proportion of patients with a partner was 80% (571/711); 19% women (108/571). In the intervention group, 48% (141/293) had a participating partner in ≥1 lifestyle program. Overall, the presence of a partner was associated with patients' successful LRF modification (adjusted risk ratio (aRR) 1.93, 95% confidence interval (CI) 1.40-2.51). A participating partner was associated with successful weight reduction (aRR 1.73, 95% CI 1.15-2.35). Conclusion: The presence of a partner is associated with LRF improvement in patients with CAD. Moreover, patients with partners participating in lifestyle programs are more successful in reducing weight. Involving partners of CAD patients in weight reduction interventions should be considered in routine practice. Keywords: (Mesh): Secondary prevention; Coronary artery disease; Risk reduction behaviour; Social support; Spouses

Physical and Cognitive Functioning After 3 Years Can Be Predicted Using Information From the Diagnostic Process in Recently Diagnosed Multiple Sclerosis

Objective\ud To predict functioning after 3 years in patients with recently diagnosed multiple sclerosis (MS).\ud \ud Design\ud Inception cohort with 3 years of follow-up. At baseline, predictors were obtained from medical history taking, neurologic examination, and magnetic resonance imaging (MRI).\ud \ud Setting\ud Neurology outpatient clinic.\ud \ud Participants\ud Patients with MS (N=156); 146 with complete follow-up.\ud \ud Interventions\ud Not applicable.\ud \ud Main Outcome Measures\ud Inability to walk at least 500m, impaired dexterity, cognitive impairments, incontinence, inability to drive a car or use public transportation, social dysfunction, and reliance on a disability pension.\ud \ud Results\ud Clinical prediction rules were constructed for the models that were well calibrated (sufficient agreement between predicted and observed outcomes, based on visual inspection of calibration curves) and that showed sufficient discrimination (area under the receiver operation characteristic curve >.70) after internal bootstrap validation. The models for the inability to walk at least 500m, impaired dexterity, and cognitive impairments were well calibrated. Discrimination was sufficient for all 7 models, except the one predicting social dysfunction (.67). The inability to walk at least 500m was predicted by the perceived ability to walk, impairment of the cerebellar tract, and the number of MRI lesions in the spinal cord. Impaired dexterity was predicted by the perceived ability to use the hands, impairments of the pyramidal, cerebellar, and sensory tracts, and the T2-weighted infratentorial lesion load. Cognitive impairment was predicted by age, gender, the perceived ability to concentrate, and the T2-weighted supratentorial lesion load.\ud \ud Conclusions\ud Inability to walk at least 500m, impaired dexterity, and cognitive impairments can be predicted with predictors that are derived from medical history taking, neurologic examination, and MRI shortly after a definite diagnosis of MS has been made.\ud \u

Peroxicretion: a novel secretion pathway in the eukaryotic cell

Background: Enzyme production in microbial cells has been limited to secreted enzymes or intracellular enzymes followed by expensive down stream processing. Extracellular enzymes consists mainly of hydrolases while intracellular enzymes exhibit a much broader diversity. If these intracellular enzymes could be secreted by the cell the potential of industrial applications of enzymes would be enlarged. Therefore a novel secretion pathway for intracellular proteins was developed, using peroxisomes as secretion vesicles. Results: Peroxisomes were decorated with a Golgi derived v-SNARE using a peroxisomal membrane protein as an anchor. This allowed the peroxisomes to fuse with the plasma membrane. Intracellular proteins were transported into the peroxisomes by adding a peroxisomal import signal (SKL tag). The proteins which were imported in the peroxisomes, were released into the extracellular space through this artificial secretion pathway which was designated peroxicretion. This concept was supported by electron microscopy studies. Conclusion: Our results demonstrate that it is possible to reroute the intracellular trafficking of vesicles by changing the localisation of SNARE molecules, this approach can be used in in vivo biological studies to clarify the different control mechanisms regulating intracellular membrane trafficking. In addition we demonstrate peroxicretion of a diverse set of intracellular proteins. Therefore, we anticipate that the concept of peroxicretion may revolutionize the production of intracellular proteins from fungi and other microbial cells, as well as from mammalian cells.