Corpus callosum index and long-term disability in multiple sclerosis patients

Prediction of long-term disability in patients with multiple sclerosis (MS) is essential. Magnetic resonance imaging (MRI) measurement of brain volume may be of predictive value but sophisticated MRI techniques are often inaccessible in clinical practice. The corpus callosum index (CCI) is a normalized measurement that reflects changes of brain volume. We investigated medical records and 533 MRI scans at diagnosis and during clinical follow-up of 169 MS patients (mean age 42±11years, 86% relapsing-remitting MS, time since first relapse 11±9years). CCI at diagnosis was 0.345±0.04 and correlated with duration of disease (p=0.002; r=−0.234) and expanded disability status scale (EDSS) score at diagnosis (r=−0.428; p<0.001). Linear regression analyses identified age, duration of disease, relapse rate and EDSS at diagnosis as independent predictors for disability after mean of 7.1years (Nagelkerkes' R:0.56). Annual CCI decrease was 0.01±0.02 (annual tissue loss: 1.3%). In secondary progressive MS patients, CCI decrease was double compared to that in relapsing-remitting MS patients (p=0.04). There was a trend of greater CCI decrease in untreated patients compared to those who received disease modifying drugs (p=0.2). CCI is an easy to use MRI marker for estimating brain atrophy in patients with MS. Brain atrophy as measured with CCI was associated with disability progression but it was not an independent predictor of long-term disabilit

Fatigue and progression of corpus callosum atrophy in multiple sclerosis

Fatigue is one of the most disabling symptoms in multiple sclerosis (MS) patients. There is no or only weak correlation between conventional magnetic resonance imaging (MRI) parameters and level of fatigue. The aim of this study was to investigate the relationship between progression of corpus callosum (CC) atrophy and fatigue in MS patients. This was a cohort study in 70 patients with relapsing form of MS (RRMS) and serial MRIs over a mean follow-up of 4.8years [67% female, mean age 42±11years, mean disease duration 9.7±7.6years, mean Expanded Disability Status Scale (EDSS) 2.8±1.6]. Fatigue was assessed by the Fatigue Severity Scale (FSS). CC size was measured with the CC index (CCI). In total, 40% of the patients suffered from fatigue (mean FSS score 5.3±1.1) and 60% patients had no fatigue (mean FSS score of 2.1±1). Patients with fatigue had higher EDSS scores (p=0.01) and CC atrophy was more pronounced in patients with fatigue (−21.8 vs. −12.1%, p=0.005). FSS correlated with CCI change over time (r=−0.33; p=0.009) and EDSS (p=0.008; r=0.361). The association between annualized CCI change and FSS was independent from EDSS, disease duration, gender and age in a multivariate linear regression analysis (p<0.001). Progression of CC atrophy may play a role in the evolution of MS-related fatigu

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients

The anti-α4 monoclonal antibody natalizumab inhibits lymphocyte extravasation into the central nervous system and increases peripheral T and B lymphocytes in multiple sclerosis patients. To investigate whether the lymphocyte accumulation was due to a higher lymphocyte production, an altered homeostasis, or a differential transmigration of lymphocyte subsets through endothelia, T-cell receptor excision circles and kappa-deleting recombination excision circles were quantified before and after treatment, T-cell receptor repertoire was analyzed by spectratyping, and T- and B-lymphocyte subset migration was studied using transwell coated with vascular and lymphatic endothelial cells. We found that the number of newly produced T and B lymphocytes is increased because of a high release and of a low propensity of naïve subsets to migrate across endothelial cells. In some patients this resulted in an enlargement of T-cell heterogeneity. Because new lymphocyte production ensures the integrity of immune surveillance, its quantification could be used to monitor natalizumab therapy safety

Spatial and Temporal High Processing of Visual and Auditory Stimuli in Cervical Dystonia.

OBJECTIVE: Investigation of spatial and temporal cognitive processing in idiopathic cervical dystonia (CD) by means of specific tasks based on perception in time and space domains of visual and auditory stimuli. BACKGROUND: Previous psychophysiological studies have investigated temporal and spatial characteristics of neural processing of sensory stimuli (mainly somatosensorial and visual), whereas the definition of such processing at higher cognitive level has not been sufficiently addressed. The impairment of time and space processing is likely driven by basal ganglia dysfunction. However, other cortical and subcortical areas, including cerebellum, may also be involved. METHODS: We tested 21 subjects with CD and 22 age-matched healthy controls with 4 recognition tasks exploring visuo-spatial, audio-spatial, visuo-temporal, and audio-temporal processing. Dystonic subjects were subdivided in three groups according to the head movement pattern type (lateral: Laterocollis, rotation: Torticollis) as well as the presence of tremor (Tremor). RESULTS: We found significant alteration of spatial processing in Laterocollis subgroup compared to controls, whereas impairment of temporal processing was observed in Torticollis subgroup compared to controls. CONCLUSION: Our results suggest that dystonia is associated with a dysfunction of temporal and spatial processing for visual and auditory stimuli that could underlie the well-known abnormalities in sequence learning. Moreover, we suggest that different movement pattern type might lead to different dysfunctions at cognitive level within dystonic population

Treatment with Natalizumab in Relapsing–Remitting Multiple Sclerosis Patients Induces Changes in Inflammatory Mechanism

Natalizumab is a widely accepted drug for the relapsing–remitting subtype of multiple sclerosis (RRMS). The present longitudinal exploratory study in RRMS patients analyzes the effects of natalizumab treatment on the levels of pro-inflammatory and anti-inflammatory cytokine protein levels and also the frequency and suppressor function of regulatory T cells. Flow cytometry was used to determine cytokines and regulatory T cell frequency while regulatory T cell suppressor function was assayed in vitro at different time-points after starting with natalizumab. Results showed serum levels of pro-inflammatory interferon gamma and interleukin (IL)-12p70, as well as anti-inflammatory IL-4 and IL-10, were elevated just a few hours or days after first IV infusion of natalizumab. Interestingly, other cytokines like IL-5 or IL-13 were also elevated while pro-inflammatory IL-17, IL-2, and IL-1β increased only after a long-term treatment, suggesting different immune mechanisms. In contrast, we did not observe any effect of natalizumab treatment on regulatory T cell frequency or activity. In conclusion, these results suggest natalizumab has other immunological effects beyond VLA-4 interaction and inhibition of CNS extravasation, the relevance of which is as yet unknown and warrants further investigation

Sensitivity to heat in MS patients: a factor strongly influencing symptomology - an explorative survey

<p>Abstract</p> <p>Background</p> <p>Many individuals diagnosed with Multiple Sclerosis (MS) are sensitive to increased body temperature, which has been recognized as correlating with the symptom of fatigue. The need to explore this association has been highlighted. The aim of this study was to investigate the occurrence of heat sensitivity and its relations to disease course, disability, common MS-related symptoms and ongoing immunosuppressive treatments among individuals 65 years of age or younger diagnosed with MS.</p> <p>Methods</p> <p>A cross-sectional designed survey was undertaken. A questionnaire was sent to MS-patients with an Expanded Disability Status Score (EDSS) in the interval of 0-6.5 and who were between 20 and 65 years of age, living in an eastern region of Sweden (n = 334). Besides occurrence of heat sensitivity (Yes/No) and corresponding questions, the Fatigue Severity Scale (FSS), the MS-related symptom checklist and the Perceived Deficit Questionnaire (PDQ) were included. Data were analysed in relation to data level using Chi-square, Mann Whitney U-test, and Student's t-test. Pearson's and Spearman's correlations were calculated. In the logistic regression analyses (enter) dichotomized MS-symptoms were used as dependent variables, and EDSS, disease-course, time since onset, heat-sensitivity, age and sex (female/male) were independent variables. In the linear regression analyses, enter, mean FSS and summarized PDQ were entered as dependent variables and EDSS, disease-course, time since onset, heat sensitivity, age and sex (female/male) were independent variables.</p> <p>Results</p> <p>Of the responding patients (n = 256), 58% reported heat sensitivity. The regression analyses revealed heat sensitivity as a significant factor relating not only to fatigue (p < 0.001), but also to several other common MS symptoms such as pain (p < 0.001), concentration difficulties (p < 0.001), and urination urgency (p = 0.009).</p> <p>Conclusions</p> <p>Heat sensitivity in MS patients is a key symptom that is highly correlated with disabling symptoms such as fatigue, pain, concentration difficulty and urination urgency.</p

Haptic Perception of Object Curvature in Parkinson's Disease

The haptic perception of the curvature of an object is essential for adequate object manipulation and critical for our guidance of actions. This study investigated how the ability to perceive the curvature of an object is altered by Parkinson's disease (PD).Eight healthy subjects and 11 patients with mild to moderate PD had to judge, without vision, the curvature of a virtual "box" created by a robotic manipulandum. Their hands were either moved passively along a defined curved path or they actively explored the curved curvature of a virtual wall. The curvature was either concave or convex (bulging to the left or right) and was judged in two locations of the hand workspace--a left workspace location, where the curved hand path was associated with curved shoulder and elbow joint paths, and a right workspace location in which these joint paths were nearly linear. After exploring the curvature of the virtual object, subjects had to judge whether the curvature was concave or convex. Based on these data, thresholds for curvature sensitivity were established. The main findings of the study are: First, 9 out 11 PD patients (82%) showed elevated thresholds for detecting convex curvatures in at least one test condition. The respective median threshold for the PD group was increased by 343% when compared to the control group. Second, when distal hand paths became less associated with proximal joint paths (right workspace), haptic acuity was reduced substantially in both groups. Third, sensitivity to hand trajectory curvature was not improved during active exploration in either group.Our data demonstrate that PD is associated with a decreased acuity of the haptic sense, which may occur already at an early stage of the disease