Gabriel Pardo

Reduced retinal nerve fiber layer and macular thickness in patients with multiple sclerosis with no history of optic neuritis identified by the use of spectral domain high-definition optical coherence tomography

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS), with both inflammatory and degenerative components. The visual system is frequently involved, often in the form of visual loss from optic neuritis (ON). Retinal nerve fiber layer (RNFL) loss has been demonstrated in individuals with MS, not only in those with previous ON but also in absence of historical evidence of previous acute inflammation/demyelination of the optic nerve. Peripapillary RNFL measurements of all quadrants, central macular thickness, and average macular thickness were performed in 32 eyes of healthy volunteers and 60 eyes of individuals with a diagnosis of relapsing remitting MS using high definition spectral domain optical coherence tomography (HD-OCT). Both the Macular Cube 512 × 128 scan and RNFL measurement by the Optic Disc Cube 200 × 200 protocol were performed on all eyes. Eyes of individuals with MS with no previous ON had significantly decreased overall RNFL thickness (89.1 μm) compared to controls (98.0 μm) (p < 0.05). MS mainly affected the temporal quadrant (56.6 μm versus [vs.] 67.8 μm) (p < 0.05), and inferior quadrant (117.9 μm vs. 132.1 μm) (p < 0.05), respectively. Also, the patients with MS demonstrated significantly decreased average macular thickness (280 μm) compared to the control group (287 μm) (p < 0.05). A significant correlation between RNFL and average macular thickness was also found in eyes of patients with MS (r = 0.69, p < 0.01). HD-OCT is a quick, inexpensive and promising tool to detect subclinical changes in RNFL and macular thickness in individuals with MS. Longitudinal studies should be encouraged to examine disease progression over time in individuals with MS.

Assessment of Postural Balance in Multiple Sclerosis

Compromised postural balance is a common manifestation of multiple sclerosis (MS). Effective quantitative methods of assessing postural imbalance are needed to help clinicians evaluate progression of this impairment. The primary objective of this study was to compare postural balance in MS patients and healthy controls using a standard screening tool, the Berg Balance Scale (BBS), as well as a more technically sophisticated device, the NeuroCom SMART Balance Master (NeuroCom International, Inc, Clackamas, OR). The study participants consisted of 14 individuals diagnosed with MS and 10 healthy controls. Each participant was assessed with the BBS and also underwent six different balance tests using the NeuroCom, most comprising several subcomponent measures. Assessment with the BBS showed significantly more postural instability in the MS group than in the control group (P < .05). Testing with the NeuroCom showed significantly more postural instability in the MS group than in the control group on two of the ...

IFN-β Treatment Requires B Cells for Efficacy in Neuroautoimmunity

IFN-β remains the most widely prescribed treatment for relapsing remitting multiple sclerosis. Despite widespread use of IFN-β, the therapeutic mechanism is still partially understood. Particularly, the clinical relevance of increased B cell activity during IFN-β treatment is unclear. In this article, we show that IFN-β pushes some B cells into a transitional, regulatory population that is a critical mechanism for therapy. IFN-β treatment increases the absolute number of regulatory CD19+CD24++CD38++ transitional B cells in peripheral blood relative to treatment-naive and Copaxone-treated patients. In addition, we found that transitional B cells from both healthy controls and IFN-β–treated MS patients are potent producers of IL-10, and that the capability of IFN-β to induce IL-10 is amplified when B cells are stimulated. Similar changes are seen in mice with experimental autoimmune encephalomyelitis. IFN-β treatment increases transitional and regulatory B cell populations, as well as IL-10 secretion in the spleen. Furthermore, we found that IFN-β increases autoantibody production, implicating humoral immune activation in B cell regulatory responses. Finally, we demonstrate that IFN-β therapy requires immune-regulatory B cells by showing that B cell–deficient mice do not benefit clinically or histopathologically from IFN-β treatment. These results have significant implications for the diagnosis and treatment of relapsing remitting multiple sclerosis.

A multicenter study of the predictors of adherence to self-injected glatiramer acetate for treatment of relapsing-remitting multiple sclerosis

Treatment with disease-modifying immunomodulators is recommended for patients with relapsing-remitting MS (RRMS). However, continuous adherence to treatment with these injected therapies can be challenging. The main objective was to examine the predictors of adherence to glatiramer acetate using a study model derived from Prochaska’s transtheoretical model of change. We conducted a 12-week, prospective, observational study. Potential predictors included readiness stage, MS self-efficacy, decisional balance (pros and cons of self-injection), and injection competence. Adults with RRMS, either treatment-naïve (TN) or treatment-experienced (TE), taking glatiramer acetate for the first time were studied. Interventions (including injection training) were implemented to promote adherence. The evaluable population included 146 TN patients and 88 TE patients who had previously discontinued beta-interferons. Adherence rates did not differ between TN and TE groups (86% for both at week 12); however, predictors of adherence did. For TN patients, greater functional self-efficacy, higher self-injection competence at baseline, and improvement in self-injection competence over the first month of therapy predicted adherence. For TE patients, lower body mass index and longer duration of MS predicted adherence. Interventions to improve self-efficacy and self-injection competence should be a priority when treating TN patients. Behavioral predictors of adherence in TE patients warrant further study.

Evaluation of Dalfampridine Extended Release 5 and 10 mg in Multiple Sclerosis A Randomized Controlled Trial

BACKGROUND Dalfampridine extended-release (ER) tablets, 10 mg twice daily, have been shown to improve walking in people with multiple sclerosis. We evaluated the safety and efficacy of dalfampridine-ER 5 mg compared with 10 mg. METHODS Patients were randomized to double-blind treatment with twice-daily dalfampridine-ER tablets, 5 mg (n = 144) or 10 mg (n = 143), or placebo (n = 143) for 4 weeks. Primary efficacy endpoint was change from baseline walking speed by the Timed 25-Foot Walk 3 to 4 hours after the last dose. At 40% of sites, 2-week change from baseline walking distance was measured by the 6-Minute Walk test. RESULTS At 4 weeks, walking speed changes from baseline were 0.363, 0.423, and 0.478 ft/s (placebo, dalfampridine-ER 5 mg, and dalfampridine-ER 10 mg, respectively [P = NS]). Post hoc analysis of average changes between pretreatment and on-treatment showed that relative to placebo, only dalfampridine-ER 10 mg demonstrated a significant increase in walking speed (mean ± SE): 0.443 ± 0.042 ft/s versus 0.303 ± 0.038 ft/s (P = .014). Improvement in 6-Minute Walk distance was significantly greater with dalfampridine-ER 10 mg (128.6 ft, P = .014) but not with 5 mg (76.8 ft, P = .308) relative to placebo (41.7 ft). Adverse events were consistent with previous studies. No seizures were reported. CONCLUSIONS Dalfampridine-ER 5 and 10 mg twice daily did not demonstrate efficacy on the planned endpoint. Post hoc analyses demonstrated significant increases in walking speed relative to placebo with dalfampridine-ER 10 mg. No new safety signals were observed.

Arterial Compliance in Multiple Sclerosis: A Pilot Study

A reduction in arterial compliance in patients with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus has been previously reported. It is caused by the effect that systemic inflammation has on the cardiovascular system. Multiple sclerosis (MS), an immune-mediated disease that exclusively affects the central nervous system (CNS), has a significant inflammatory component that is limited to that compartment. The potential effects of its inflammatory mediators in the cardiovascular system are largely unknown. Purpose: To examine large (C1) and small arterial compliance (C2) in patients with MS and compare them with healthy age-matched controls. To also determine whether any differences in C1 and C2 indices between participants diagnosed with relapsing remitting MS (RR-MS), secondary progressive MS (SP-MS), and controls exist. Methods: A total of 26 men and women between the ages of 18 and 64 diagnosed with MS and 25 healthy controls volunteered for this study. Arterial compliance was measured by using pulse contour analysis (PCA), which records and analyzes the blood pressure waveform data from the Arterial Pulse Wave Sensors. Results: Significant differences in C1 and C2 were found between young RR-MS and healthy young controls (P < .05), with the MS group showing lower arterial C1 and C2 compliance. No significant differences (P > .05) were seen for C1 or C2 values between older RR-MS, SP-MS, and healthy controls. Conclusion: Arterial compliance is significantly compromised in young individuals with MS, compared with age-matched controls, but not for older individuals, suggesting a systemic effect of an inflammatory process that predominantly affects the CNS.

Self-efficacy, Physical Activity and QOL in People with MS

Self-Efficacy is part of the social-cognitive theory defined as the belief that one can successfully cope with challenging situations and attain certain goals. It has been suggested this principle can be applied to physical and psychological quality of life in individuals with Multiple Sclerosis (MS). Objective: To examine if self-efficacy and physical activity have relationships with quality of life (QOL) in individuals with MS. Methods: 109 individuals with MS participated in this study. Each individual completed the Multiple Sclerosis Self-Efficacy scale (MSSE), the Multiple Sclerosis Impact Scale (MSIS-29), and the Good in Leisure-Time Exercise Questionnaire (GLTEQ). Pearson product moment correlation coefficients were computed for self-efficacy, physical activity and QOL. Results: The sample (n=109) was composed as follows, females (75%), relapsing remitting form of MS (81%), married (68%), employed (44%). Time since MS diagnosis was 7.6 years (SE=0.62). There were moderately high negative correlations between MSSE and QOL physical component (r=-0.65, p<0.01) and psychological component (r=-0.63, p<0.01), indicating that individuals with increased sense of self-efficacy experienced less psychological issues and an increased level of participation in physical tasks. There was a low negative but significant correlation between total time spent in leisure activity and QOL physical component (r=-0.21, p<0.05), but not for QOL psychological component. Physical activity has a negative correlation with physical impact of QOL (r=-0.21, p<0.05) and no correlation with psychological component (p>0.05). Conclusion: The results of this study demonstrate that with increased self-efficacy there is an increase in QOL on both physical and psychological components, which is important for increased independence and functionality in individuals with MS.

Dalfampridine Effects Beyond Walking Speed in Multiple Sclerosis

BACKGROUND Dalfampridine extended release (ER) improves walking in people with multiple sclerosis (MS), as demonstrated by walking speed improvement. This exploratory study evaluated treatment effects of dalfampridine-ER on gait, balance, and walking through treatment withdrawal and reinitiation. METHODS Dalfampridine-ER responders, based on Timed 25-Foot Walk (T25FW) assessment before study entry, were included in this open-label, three-period, single-center study. Period 1: on-drug evaluations performed at screening and 1 week after screening. Period 2: dalfampridine-ER withdrawal and off-drug evaluations (days 5 and 11). Period 3: dalfampridine-ER reinitiation/final on-drug evaluation (day 15). PRIMARY OUTCOME VARIABLES NeuroCom composite scores for gait and balance; balance was evaluated if gait changes were significant. Secondary variables: individual NeuroCom scores, walking speed (T25FW) and distance (2-Minute Walk Test [2MWT]), and balance (Berg Balance Scale [BBS]). RESULTS All 20 patients completed the study: mean age, 53.1 years; mean MS duration, 11.3 years; mean time taking dalfampridine-ER, 315.3 days. NeuroCom gait composite scores worsened during period 2 relative to period 1 and improved during period 3; the mean ± SD difference in gait composite scores on drug was 4.03 ± 1.51 points (P = .015). Balance composite scores did not change significantly. Improvements were observed for off-drug versus on-drug for T25FW (0.36 ft/sec, P < .001), 2MWT (25.4 ft, P = .006), and BBS (1.7 points, P = .003). Safety profile was consistent with previous studies. CONCLUSIONS Significant improvements in gait, walking speed, distance, and balance were demonstrated by dalfampridine-ER reinitiation after a 10-day withdrawal period.

Association of vitamin D deficiency with RNFL thickness in MS individuals without history of optic neuritis

UNLABELLED Vitamin D deficiency has been associated with both increased risk and severity of Multiple Sclerosis (MS) as it has a modulating effect on the immune process that causes inflammation/demyelination and axonal damage. Optical Coherence Tomography (OCT) offers a quick, reliable and non-invasive way to assess the Retinal Nerve Fiber Layer (RNFL) and identifies axonal loss generated by either direct inflammation or from neurodegeneration. OBJECTIVE To determine the association of vitamin D and RNFL in MS patients without a history of Optic Neuritis (ON) by comparing RNFL thickness in patients that are vitamin D deficient with those having normal serum levels. METHOD The cohort of 76 MS patients underwent OCT testing to assess the RNFL thickness and macular volume, and measurement of serum 25-OH Vitamin D level. Vitamin D deficiency was defined as <30ng/ml and sufficiency as ≥30ng/ml. RESULTS A total of 131 eyes were divided in two groups: vitamin D deficient (n=86 eyes, mean=17.7ng/ml) and vitamin D sufficient (n=45 eyes, mean=40.3ng/ml). Twenty one eyes had previous ON and were excluded from this analysis. Vitamin D deficiency was identified in 66% of the participants. RNFL thickness was similar for the vitamin D deficient and sufficient groups (85.5 vs 86μm respectively, p=0.89). Significant differences were present for age with the deficient group being younger (42 years vs 51 years, p=0.005) and having shorter disease duration (7.5 years vs 11.4 years, p=0.006). CONCLUSION Vitamin D deficiency is not associated with thinning of RNFL or macular volume in MS eyes unaffected by ON. This finding suggests the role of vitamin D in modulating the severity of MS is not exerted through an influence on neurodegeneration.

Quality of Life According to Duration of Disease in Women With Low Disability in Multiple Sclerosis

The primary aim of this study was to investigate the relationship between Expanded Disability Status Scale (EDSS) scores and quality of life (QOL) in women with multiple sclerosis (MS) and low disability and whether duration of disease influenced the established relationship. Sixty-six women diagnosed with MS (44.0 ± 1.2 [standard error] years) had EDSS scores of <5.0 as determined by their neurologist. Duration of disease from time of diagnosis ranged from 2 months to 28 years, and subjects were arbitrarily divided into three groups (group 1: 0.1–10.0 years; group 2: 10.1–20.0 years; group 3: 20.1–33.0 years). After giving informed consent, all subjects completed the MS Quality of Life-54 questionnaire (MSQOL-54). Mean EDSS was 1.4 for group 1, 2.0 for group 2, and 2.1 for group 3. Group 3 had the highest score for both the physical and mental components of MSQOL-54. In general, the relationship between the functional systems (FS) of EDSS and subcomponents of MSQOL-54 were negative and low to moderate in...