Relapsing-remitting Patients Research Articles

Sodium intake is associated with increased disease activity in multiple sclerosis

BackgroundRecently, salt has been shown to modulate the differentiation of human and mouse Th17 cells and mice that were fed a high-sodium diet were described to develop more aggressive courses...

Do Textured Insoles Affect Postural Control and Spatiotemporal Parameters of Gait and Plantar Sensation in People With Multiple Sclerosis?

BackgroundBalance and gait deficits are common in people with multiple sclerosis (MS). Physical interventions directed at improving balance and walking abilities have been implemented using various approaches. Nonetheless, no mode of training has been universally agreed upon. ObjectivesTo determine whether textured insoles have immediate effects on postural control and spatiotemporal parameters of gait and plantar sensation in people with people with MS and to explore effects 4 weeks after insole wear as to whether any immediate effects are maintained over time. DesignWithin-subject experimental study with a 4-week intervention phase. SettingsMultiple Sclerosis Center, Center of Advanced Technologies in Rehabilitation, Sheba Medical Center, Tel-Hashomer, Israel. ParticipantsTwenty-five relapsing-remitting patients diagnosed with MS, 16 women and 9 men, aged 49.6 years (standard deviation = 6.5 years). InterventionTextured insoles customized according to foot size and adapted to the participant's casual shoes. Main outcome measuresSpatiotemporal parameters of gait and center of pressure (CoP) excursions during static postural control were studied using the Zebris FDM-T Treadmill. Light-touch and pressure-sensation thresholds were determined using the Semmes-Weinstein monofilaments test. ResultsTextured insoles did not alter static postural control parameters when examined with eyes open. Examination during the eyes-closed task demonstrated an immediate reduction in the CoP path length (298.4 mm, standard error = 49.7 mm, versus 369.9 mm, SE = 56.3 mm; P = .04) and sway rate (12.0 mm/s, standard error = 1.4 mm/s, versus 15.1 mm/s, standard error = 1.6 mm/s; P = .03) after insertion of the textured insoles compared to casual shoes alone. These findings were maintained at termination of the insole 4-week intervention period. In terms of spatiotemporal parameters of gait, differences were not observed between casual shoes and shoes with textured insoles at baseline. Likewise, no differences were observed between initial and concluding gait trials. Significant differences in plantar sensitivity measures were not observed after the insole 4-week intervention phase. ConclusionsAlthough there were improvements in some aspects of balance, the efficacy of textured insoles in the MS population remains unclear.

Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients

Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17β-diol and of 17β-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis.

High frequency of antiphospholipid antibodies in relapse of multiple sclerosis: a possible indicator of inflammatory-thrombotic processes.

The exact prevalence and pathogenic role of antiphospholipid antibodies (aPL) in multiple sclerosis (MS) remain unclear. This observational laboratory-blinded study evaluated the rate of aPL positivity in healthy controls and MS patients in different disease phases to recognize their frequency and possible pathogenic meaning. Reactivity for anti-cardiolipin, anti-β2 glycoprotein I, anti-prothrombin, anti-annexin V (IgG and IgM) was studied by enzyme immunoassays in 60 healthy controls and 100 consecutive MS patients [58 relapsing-remitting (RR) patients in remission, 26 RR patients in relapse, and 16 secondary progressive patients]. The overall rate of positivity for at least one aPL was significantly higher in MS patients compared to controls (32 % vs. 7 %, respectively, p < 0.0001), and in relapsing phase compared to those remitting or secondary progressive (53.8, 20.7 and 37.5 %, respectively, p = 0.002). In the single aPL analysis, the rate of positivity was significantly higher in MS patients compared to controls for anti-prothrombin IgM (7 % vs. 0, p = 0.05), and in relapsing phase compared to remitting and secondary progressive phases for anti-β2 glycoprotein I IgM (26.9, 1.7, 6.3 %, respectively, p < 0.0001), anti-prothrombin IgM (15.4, 3.4, 6.3 %, respectively, p = 0.05) and IgG (19.2, 5.2, 0 %, respectively, p = 0.05). We showed a significant aPL increase in MS patients compared to healthy controls, particularly during disease relapse which was also associated with significantly higher values of anti-β2 glycoprotein I and anti-prothrombin. These data suggest that antiphospholipid antibody occurrence in multiple sclerosis could be related to modification of structure and function of proteins involved in the inflammatory-thrombotic processes during disease re-activation.

New Poteintial Serum Biomarkers in Multiple Sclerosis Identified by Proteomic Strategies

Proteome analysis of body fluids is a powerful tool to identify biomarkers of neurological disorders. Multiple sclerosis (MScl) is a chronic disabling disorder of central nervous system (CNS) and is regarded as an autoimmune disease to myelin components. Clinical subtypes of MScl differ in course, prognosis and response to available therapy. There is evidence of a different pattern of CNS lesions in subtypes, suggesting different immunological mechanisms are relevant in inflammatory demyelination. In order to elucidate proteome signatures, we used two-dimensional differential gel electrophoresis (2D-DIGE) to compare the protein expression profile in serum of different clinical subtypes of MScl patients and of healthy volunteers, resp. controls. Significant expression differences were detected by 2D-DIGE for 241 serum proteins, and transthyretin, zinc-alpha-2-glycoprotein, alpha-1-antitrypsin, immunoglobulin and complement factors (C4, C6 and C8) were identified as potential disease signatures for MScl patients. Three highly-expressed proteins were selected for further evaluation in individual patients by independent immunoassays, and the up-regulation of transthyretin, zinc alpha-2-glycoprotein and immunoglobulin kappa light chain was validated in sera of relapsing-remitting (CIS and RRMScl) patients, when compared to healthy donors. To present significant expression differences in PPMScl, analysis with a larger patient population is required.

Surface-based analysis reveals regions of reduced cortical magnetization transfer ratio in patients with multiple sclerosis: a proposed method for imaging subpial demyelination.

The in vivo detection of subpial cortical gray matter lesions in multiple sclerosis is challenging. We quantified the spatial extent of subpial decreases in the magnetization transfer ratio (MTR) of cortical gray matter in subjects with multiple sclerosis, as such reductions may indicate regions of cortical demyelination. We exploited the unique geometry of cortical lesions by using two-dimensional parametric surface models of the cortex instead of traditional three-dimensional voxel-wise analyses. MTR images were mapped onto intermediate surfaces between the pial and white matter surfaces and were used to compute differences between secondary-progressive MS (n = 12), relapsing-remitting MS (n = 12), and normal control (n = 12) groups as well as between each individual patient and the normal controls. We identified large regions of significantly reduced cortical MTR in secondary-progressive patients when compared with normal controls. We also identified large regions of reduced cortical MTR in 11 individual patients (8 secondary-progressive, 3 relapsing-remitting). The secondary-progressive patients showed larger areas of abnormally low MTR compared with relapsing-remitting patients both at the group level and on an individual basis. The spatial distributions of abnormal MTR preferentially involved cingulate cortex, insula, and the depths of sulci, in agreement with pathological descriptions of subpial gray matter lesion distribution. These findings suggest that our method is a plausible in vivo imaging technique for quantifying subpial cortical demyelinating lesions in patients with multiple sclerosis and, furthermore, can be applied at the typical clinical field strength of 1.5 T.

Synaptic Plasticity and PDGF Signaling Defects Underlie Clinical Progression in Multiple Sclerosis

Neuroplasticity is essential to prevent clinical worsening despite continuing neuronal loss in several brain diseases, including multiple sclerosis (MS). The precise nature of the adaptation mechanisms taking place in MS brains, ensuring protection from disability appearance and accumulation, is however unknown. Here, we explored the hypothesis that long-term synaptic potentiation (LTP), potentially able to minimize the effects of neuronal loss by providing extra excitation of denervated neurons, is the most relevant form of adaptive plasticity in stable MS patients, and it is disrupted in progressing MS patients. We found that LTP, explored by means of transcranial magnetic theta burst stimulation over the primary motor cortex, was still possible, and even favored, in stable relapsing-remitting (RR-MS) patients, whereas it was absent in individuals with primary progressive MS (PP-MS). We also provided evidence that platelet-derived growth factor (PDGF) plays a substantial role in favoring both LTP and brain reserve in MS patients, as this molecule: (1) was reduced in the CSF of PP-MS patients, (2) enhanced LTP emergence in hippocampal mouse brain slices, (3) was associated with more pronounced LTP in RR-MS patients, and (4) was associated with the clinical compensation of new brain lesion formation in RR-MS. Our results show that brain plasticity reserve, in the form of LTP, is crucial to contrast clinical deterioration in MS. Enhancing PDGF signaling might represent a valuable treatment option to maintain brain reserve and to attenuate the clinical consequences of neuronal damage in the progressive phases of MS and in other neurodegenerative disorders.

Interferon-beta and disability progression in relapsing-remitting multiple sclerosis

ObjectiveTo assess the impact of interferon (IFN)-beta treatment on the progression of unremitting disability in IFN-beta treated and untreated relapsing-remitting (RR) patients with multiple sclerosis (MS) using prospective cohort study. MethodsA cohort of 419 RRMS (236 IFN-beta-treated and 183 untreated) patients was followed for up to 7 years. Cox proportional hazards regression models adjusted for the number of relapses in the last year before first visit was used to assess the differences between the two groups for the three end points: secondary progression (SP), and sustained Expanded Disability Status Scale (EDSS) score 4 and 6. Time from disease onset was used as survival time variable. ResultsThe IFN-beta-treated group showed a highly significant reduction (hazard ratio [HR], 0.34, 95% confidence interval [CI] 0.19–0.61, p<0.001) in the risk of SP when compared with untreated patients. There were significant differences in favor of the IFN-beta-treated group for the end point EDSS score of 4 (HR=0.45, 95%CI 0.28–0.73, p=0.001) and EDSS score of 6 (HR=0.34, 95%CI 0.16–0.75, p=0.007). ConclusionThis observational study further supports the notion that IFN-beta could have potential beneficial effect on disease progression in RRMS.

The relationship between fear of falling to spatiotemporal gait parameters measured by an instrumented treadmill in people with multiple sclerosis

People with multiple sclerosis (MS) identify mobility limitations as one of the greatest challenges of this disease. Continued loss of mobility and falls are among their greatest concerns for the future. Our objective was to determine if fear of falling is associated with spatial and temporal gait parameters in persons with MS, when measured by an instrumented treadmill. This observational case control study was performed at the MS Center, Center of Advanced Technologies in Rehabilitation, Sheba Medical Center, Tel Hashomer, Israel. Sixty-eight relapsing-remitting patients diagnosed with MS, 38 women, aged 40.9 (S.D.=11.9), participated in this investigation. Twenty-five healthy subjects, 14 women, aged 39.5 (S.D.=9.4) served as controls gait controls. Gait spatiotemporal parameters were obtained using the Zebris FDM-T Treadmill (Zebris® Medical GmbH, Germany). The Falls Efficacy Scale International was used to assess the level of concern relating to falls. Forty-one people with MS were classified as highly fearful of falling. Twenty-seven patients were slightly concerned. Highly fearful of falling patients walked slower had a shorter step length, a wider base of support and prolonged double support phase compared to slightly concerned patients. Fearful patients also demonstrated elevated variability of the center of pressure (CoP) trajectory compared to slightly concerned MS patients. Fear of falling and spatiotemporal gait alterations in people with MS are linked. Additionally, variability of the CoP during walking appears to be connected with the level of concern.

What We Know About Creativity

<b>Objective:</b> We sought to establish the reliability and validity of a novel composite cognitive endpoint for monitoring improvement in memory and processing speed in future drug trials. <b>Background</b> Approximately 50% of all patients with Multiple Sclerosis have clinically significant symptoms of cognitive impairment that impact their ability to work and interfere with the quality of their home life and leisure activities. FDA officials have approved composite cognitive endpoints for the study of drug interventions for Alzheimer9s (ADAS-COG) and Schizophrenia (MATRICS), but not MS. <b>Design/Methods:</b> We administered the Selective Reminding Test (SRT), Brief Visuospatial Memory Test, Revised, PASAT, and SDMT to 60 MS patients at 4 centers twice over a 45 day timespan. These measures were chosen based on their known sensitivity to MS cognitive symptoms, the availability of alternate forms and known cross-cultural utility. Norm-referenced data was used to study the test-retest reliability of each measure. A composite measure for use as an endpoint in a drug trial was constructed based on factor structure. <b>Results:</b> Test-retest reliability for individual subtests ranged from r = .62 for the SRT delayed recall trial to .88 for the SDMT. A general composite representative of performance across measures had reliability of .91. Processing Speed and Memory composite indices were r =.89 and r =.86, respectively with modest practice effects. Secondary Progressive patients performed approximately .8 standard deviations below Relapsing-Remitting patients, with the two populations demonstrating cognitive impairment with frequencies 77% and 39%, respectively. Cognitive impairment correlated reasonably well (r = .40) with Informant reports on the Multiple Sclerosis Neuropsychological Questionnaire. <b>Conclusions:</b> The novel composite endpoint is a reliable, repeatable measure of general cognitive functioning that is sensitive to cognitive impairment in both Secondary Progressive and Relapsing –Remitting MS patients. Supported by: Biogen-Idec. <b>Disclosure:</b> Dr. DeLuca has received personal compensation for activities with Kessler Foundation Research Center and Biogen Idec.Dr. DeLuca has received research support from Biogen Idec. Dr. Foley has received personal compensation for activities with Biogen Idec. Dr. Foley has received research support from Bayer Pharmaceuticals. Dr. Benedict has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Serono, Inc., Novartis, Merck &amp; Co., Inc. and Pfizer Inc as speaker, consultant and/or member on advisory panel. Dr. Benedict has received research support from Memen Pharmaceuticals, Shire Pharmaceuticals and Biogen Idec. Dr. Caruso has received personal compensation for activities with Biogen Idec as a consultant. Dr. Caruso has received research support from Biogen Idec. Dr. Erlanger has received personal compensation for activities with Biogen Idec as a consultant. Dr. Erlanger has received research support from Biogen Idec. Dr. Kaushik has received personal compensation for activities with Panmedix as a research coordinator. Dr. Kaushik has received research support from Biogen-Idec.

Cognition in Early Relapsing-Remitting Multiple Sclerosis: Consequences May Be Relative to Working Memory

The Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed,as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages.

Quantifying Gait Impairment Using an Instrumented Treadmill in People with Multiple Sclerosis

Background and Objective. Treadmill gait analysis has been proposed as an attractive alternative for overground walking measuring systems. The purpose of this study was twofold: first to determine spatiotemporal parameters of treadmill gait in patients with multiple sclerosis (MS) and second to examine whether these parameters are associated with specific functional impairments in this cohort. Method. Eighty-seven relapsing-remitting patients diagnosed with MS, 50 women and 37 men, aged 40.9 ± 11.9 with an expanded disability status scale (EDSS) score of 2.7 ± 1.6, participated in this study. Twenty-five apparently healthy subjects, 14 women and 11 men, aged 38.5 ± 9.4, served as controls. Spatiotemporal gait parameters were obtained using the Zebris FDM-T Treadmill (Zebris Medical GmbH, Germany). People with MS demonstrated significantly shorter steps, extended stride time, wider base of support, longer step time, reduced single support phase, and a prolonged double support phase compared to the healthy controls. The EDSS score was significantly correlated with all spatiotemporal gait parameters. Conclusion. The instrumented treadmill may be an effective tool in assessing ambulation capabilities of people with MS.

Treatment experience, burden, and unmet needs (TRIBUNE) in Multiple Sclerosis study: the costs and utilities of MS patients in The Netherlands

Background:Multiple sclerosis (MS) is an important, highly disabling neurological disease, common among young adults in The Netherlands. Nevertheless, only a few studies to date have measured the burden imposed by MS on society in The Netherlands.Objectives:To estimate the cost and quality-of-life associated with MS in The Netherlands, while focusing on the burden of relapses and increasing disease severity.Methods:MS patients in The Netherlands (n = 263) completed a web-based questionnaire which captured information on demographics, disease characteristics and severity (Expanded Disability Status Scale [EDSS]), co-morbidities, relapses, resource consumption, utilities, fatigue and activities of daily living (ADL).Results:Most patients included in the study were receiving treatment for MS (76% of the sample). The mean cost per patient per year increased with worsening disability and was estimated at €30,938, €51,056, and €100,469 for patients with mild (EDSS 0–3), moderate (EDSS 4–6.5), and severe (EDSS 7–9) disability, respectively. The excess cost of relapses was estimated at €8195 among relapsing-remitting patients with EDSS score ≤5. The quality-of-life of patients decreased with disease progression and existence of relapses.Conclusions:The cost of MS in The Netherlands was higher compared to the results of previous studies. The TRIBUNE study provides an important update on the economic burden of MS in The Netherlands in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue.Conclusions:Study limitations:

Involvement of Oxidative Stress in Occurrence of Relapses in Multiple Sclerosis: The Spectrum of Oxidatively Modified Serum Proteins Detected by Proteomics and Redox Proteomics Analysis

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. Several evidences suggest that MS can be considered a multi-factorial disease in which both genetics and environmental factors are involved. Among proposed candidates, growing results support the involvement of oxidative stress (OS) in MS pathology. The aim of this study was to investigate the role of OS in event of exacerbations in MS on serum of relapsing-remitting (RR-MS) patients, either in relapsing or remitting phase, with respect to serum from healthy subjects. We applied proteomics and redox proteomics approaches to identify differently expressed and oxidatively modified proteins in the low-abundant serum protein fraction. Among differently expressed proteins ceruloplasmin, antithrombin III, clusterin, apolipoprotein E, and complement C3, were up-regulated in MS patients compared with healthy controls. Further by redox proteomics, vitamin D-binding protein showed a progressive trend of oxidation from remission to relapse, respect with controls. Similarly, the increase of oxidation of apolipoprotein A-IV confirmed that levels of OS are elevated with the progression of the disease. Our findings support the involvement of OS in MS and suggest that dysfunction of target proteins occurs upon oxidative damage and correlates with the pathology.

Cognitive Reserve and Symptom Experience in Multiple Sclerosis: A Buffer to Disability Progression Over Time?

ObjectiveTo investigate the possible buffering effect of cognitive reserve on symptom experience for multiple sclerosis (MS) disease course. DesignSecondary analysis of longitudinal data from the North American Research Committee on MS Registry. SettingRegistry study and web-based supplemental survey. ParticipantsPeople with MS (N=859). InterventionsNot applicable. Main Outcome MeasuresTwo health outcome measures, the Symptom Inventory and the Performance Scales, were collected biannually over 1 and 6 years, respectively. Active and passive cognitive reserve was measured using the Stern Leisure Activities and the Sole-Padulles Childhood Enrichment tools, respectively. Linear regression, chi-square, multilevel random-effects modeling, and classification and regression tree modeling were used to compare cross-sectional means, disease course by cognitive reserve, longitudinal trajectories, and active cognitive reserve item endorsement by disability groups, respectively. ResultsPatients with high-active reserve had a lesser symptom burden than those with low-active reserve independent of passive reserve (P<.01). Cognitive reserve was associated with course of disease, such that high-active patients were overrepresented among relapsing-remitting patients, and underrepresented among patients with progressive disease (χ2=14.7, P<.03). Longitudinal modeling revealed a significant interaction of active reserve and time in mobility, fatigue, and overall disability in the whole sample (P<.05 in all comparisons). Among patients whose disability trajectories changed over time, active cognitive reserve was associated with less deterioration (P<.001). Passive cognitive reserve evidenced no effect in the longitudinal analyses. Active cognitive reserve scores across disability groups had a similar range but comprised different items, indicating that patients maintain active cognitive reserve with different activities as the disease progresses. ConclusionsOur findings suggest that active cognitive reserve is a buffer for functional limitation across disability groupings. Cognitive reserve may provide an alternative lens for thinking about the disease course of MS, providing a longer “runway” until disability accrual through cortical remodeling. Loss of cognitive reserve may explain the onset of progressive disease in MS.

Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

Intrathecal IgG synthesis in relapsing-remitting multiple sclerosis (MS) is decreased by natural human alpha interferon

Intrathecal IgG synthesis (IT IgG Syn) is an established biomarker used for the diagnosis of multiple sclerosis (MS). Earlier studies used this biomarker to assess the impact of 2 different synthetic forms of interferon alpha (IFN-α) in chronic progressive MS. Unexpectedly, IT IgG synthesis was increased by this treatment. For the first time, we have assessed this parameter in relapsing-remitting patients to measure the impact of natural IFN-α treatment in a doseranging study in six dosage groups (5, 10, 15, 20, 25, & 30 MIU). We have found that IFN-α normalized IT IgG Synthesis at 12 weeks treatment for all dosage groups. Two weeks after stopping IFN-α results rose slightly. At 52 weeks, 28 weeks after stopping IFN-a results revealed cessation of IT IgG Synthesis in half of the patients (15, 20, 25 MIU weekly). These results reflect different outcomes for relapsing-remitting patients vs. chronic progressive patients. They may, however, reflect differences in the biological properties of the interferon products used. An optimal range of dosage with natural human IFN-α dosage for MS is suggested by the results.

Validation of a new quality of life scale related to multiple sclerosis and relapses

Multiple sclerosis (MS) has a significant impact on all aspects of patient quality of life (QoL). Furthermore, the fear of relapses and the feelings of patients during relapses must be taken into account in care. The objective of this work was to validate the PERSEPP scale ("PERception de la Sclérose En Plaques et de ses Poussées"), a new QoL evaluation scale for relapsing-remitting forms of MS. Relapsing-remitting patients were included in a multicenter study. Various validation criteria of this scale were analyzed: acceptability, construct validity (internal and external validity), and reliability (internal consistency and reproducibility test-retest). Responsiveness will be studied in order to complete the validation process. The responses of 305 MS patients were analyzed. The process of reducing the items led us to retain 66 items of a total of 112 items. The 66-item PERSEPP scale (final version) was well accepted. Five dimensions (33 items) make up the scale: social support (α = 0.81), relationship difficulties (α = 0.71), fatigue (α = 0.74), state of mind and associated sleep disorders (α = 0.78), and time perspective (α = 0.75). Three additional modules (33 items) explore coping (α = 0.60), symptoms (α = 0.89), and treatment (α = 0.92). Test-retest reliability, measured by the intraclass correlation coefficient (ICC), was acceptable (0.72 < ICC < 0.92). The PERSEPP scale has been validated and could be used in clinical trials and in daily practice. Additional studies will then complete the validation process.

Disability caused by multiple sclerosis is associated with the number of extra cranial venous stenoses: possible improvement by venous angioplasty. Results of a prospective study

Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in patients with multiple sclerosis (MS). The hypothesis of the vascular aetiology provides a new approach in the investigation and treatment of MS. Our open-label study included 94 MS patients who fulfilled ultrasound sonographic criteria required for CCSVI. The internal jugular and/or azygous veins by a catheter venography were dilated. In 34.8% of the patients unilateral, in 65.2% bilateral venous abnormalities and in 2.1% no luminal obstructions were demonstrated. The patient group with the higher disability score had a significantly higher number of venous lesions (P < 0.005). Significant improvement of clinical disability in relapsing-remitting patients was (P < 0.001) achieved. In our study no stents were used. Re-stenosis occurred in 21.7% of the patients. The number of venous narrowings is higher in more disabled patients. A significant improvement in clinical disability in the relapsing-remitting group was observed.

African ancestry is a predictor factor to secondary progression in clinical course of multiple sclerosis.

Background. Studies on the clinical course of multiple sclerosis have indicated that certain initial clinical factors are predictive of disease progression. Regions with a low prevalence for disease, which have environmental and genetic factors that differ from areas of high prevalence, lack studies on the progressive course and disabling characteristics of the disease. Objective. To analyse the long-term evolution to the progressive phase of the relapsing-remitting multiple sclerosis and its prognosis factors in mixed population. Methods. We performed a survival study and logistic regression to examine the influence of demographic and initial clinical factors on disease progression. Among 553 relapsing-remitting patients assisted at a Brazilian reference centre for multiple sclerosis, we reviewed the medical records of 150 patients who had a disease for ten or more years. Results. African ancestry was a factor that conferred more risk for secondary progression followed by age at the onset of the disease and the number of relapses in the year after diagnosis. A greater understanding of the influence of ancestry on prognosis serves to stimulate genetics and pharmacogenomics research and may clarify the poorly understood neurodegenerative progression of MS.