Amber Salter

Factors that influence adherence with disease-modifying therapy in MS

BackgroundThe complexity and cost of injection treatment can represent a formidable challenge for patients affected by a chronic illness, particularly those whose treatment is primarily preventative and only modestly effective on the more conspicuous symptomatic aspects of the disease process. The aim of this investigation was to identify which factors most influenced nonadherent behavior with the available diseasemodifying injection therapies for multiple sclerosis (MS).MethodsA multicenter, observational (threewave) study using surveys was developed and administered to patients with MS through the World Wide Web. Healthcare providers at 17 neurology clinics recruited patients for the study.ResultsA total of 798 patients responded to the baseline wave of the study (708 responded to all three waves). The nonadherence rates for all patients (missing one or more injections) across these waves remained relatively stable at 39 %, 37 %, and 36 %, respectively. The most common reason participants listed for missing injections was that they simply forgot to administer the medication (58 %). Other factors including injection-site reactions, quality of life, patients’ perceptions on the injectable medications, hope, depression, and support were also assessed in relation to adherence.ConclusionsThis study characterizes factors that are associated with failure to fully adhere with disease modifying injection therapy for MS and underscores the principles associated with optimizing adherence and its implications for effective treatment of the disease process in MS.

Randomized study combining interferon and glatiramer acetate in multiple sclerosis

A double‐blind, randomized, controlled study was undertaken to determine whether combined use of interferon β‐1a (IFN) 30μg intramuscularly weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing–remitting multiple sclerosis.

Retinal Imaging by Laser Polarimetry and Optical Coherence Tomography Evidence of Axonal Degeneration in Multiple Sclerosis

BACKGROUND Optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx) are similar yet provide information on different aspects of retinal nerve fiber layer (RNFL) structure (thickness values similar to histology for OCT vs birefringence of microtubules for GDx). OBJECTIVES To compare the ability of OCT and GDx to distinguish eyes of patients with multiple sclerosis (MS) from eyes of disease-free controls and thus identify RNFL abnormalities. We also sought to examine the capacity of these techniques to distinguish MS eyes from those without a history of optic neuritis and to correlate with visual function. DESIGN Cross-sectional study. SETTING Academic tertiary care MS center. PARTICIPANTS Eighty patients with MS (155 eyes) and 43 disease-free controls (85 eyes) underwent both OCT and GDx imaging using protocols that measure RNFL thickness. MAIN OUTCOME MEASURES Areas under the curve (AUC), adjusted for within-patient, intereye correlations, were used to compare the abilities of OCT and GDx temporal-superior-nasal-inferior-temporal average RNFL thicknesses to discriminate between MS and control eyes and to distinguish MS eyes with a history of optic neuritis. Visual function was evaluated using low-contrast letter acuity and high-contrast visual acuity. RESULTS Average peripapillary RNFL thickness (360 degrees around the optic disc) was reduced in patients with MS compared with controls for both methods. Age-adjusted AUC did not differ between OCT (0.80; 95% confidence interval [CI], 0.72-0.88) and GDx (0.78; 95% CI, 0.68-0.86; P = .38). Optical coherence tomography-measured RNFL thickness was somewhat better at distinguishing MS eyes with a history of optic neuritis from those without (OCT: AUC, 0.73; 95% CI, 0.64-0.82; GDx: AUC, 0.66; 95% CI, 0.57-0.66; P = .17). Linear correlations of RNFL thickness for OCT vs GDx were significant yet moderate (r = 0.67, P < .001); RNFL thickness measures correlated moderately and significantly with low-contrast acuity (OCT: r = 0.54, P < .001; GDx: r = 0.55, P < .001) and correlated less with high-contrast visual acuity (OCT: r = 0.44, P < .001; GDx: r = 0.32, P < .001). CONCLUSIONS Scanning laser polarimetry with variable corneal compensation measurements of RNFL thickness corroborates OCT evidence of visual pathway axonal loss in MS and provides new insight into structural aspects of axonal loss that relate to RNFL birefringence (microtubule integrity). These results support validity for RNFL thickness as a marker for axonal degeneration and support use of these techniques in clinical trials that examine neuroprotective and other disease-modifying therapies.

Relationship of optic nerve and brain conventional and non-conventional MRI measures and retinal nerve fiber layer thickness, as assessed by OCT and GDx: A pilot study

BACKGROUND Measurement of retinal nerve fiber layer (RNFL) thickness in multiple sclerosis (MS) is gaining increasing attention. OBJECTIVES To explore the relationship between RNFL thickness as measured by optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx), and conventional and non-conventional optic nerve and brain MRI measures. METHODS Twelve relapsing-remitting (RR) MS patients (12 affected and 12 unaffected eyes) and 4 age- and sex-matched normal controls (NC) (8 unaffected eyes) were enrolled. Four MS patients had a history of bilateral optic neuritis (ON), four had a history of unilateral ON, and 4 had no history of ON. Optic nerve MRI measurements included the length of T2 lesions, measurement of optic nerve atrophy, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) measures. Optic nerve atrophy was measured by a novel method with high reproducibility. Brain MRI measurements included T1 and T2 lesion volumes (LVs) and their relative MTRs, and tissue class specific atrophy, MTR and DTI measures. Measures of RNFL were evaluated with OCT and GDx. We also evaluated both high and low contrast letter acuities (LCLA) in order to determine the relationship between vision, MRI metrics, and retinal structural architecture. RESULTS LCLA, RNFL-OCT and optic nerve radius measures showed more robust differences between NC and MS patients, and between MS patients with affected and unaffected eyes. T2-LV and T1-LV, as well as gray matter atrophy, DTI and MTR measures were related to LCLA and RNFL thickness. Unique additive variance regression models showed that both brain and optic nerve MRI measures independently accounted for about 50% of the variance in LCLA and RNFL thickness. In reverse models, about 20% of the additional independent variance was explained by optic nerve or brain MRI metrics. CONCLUSIONS Measurement of RNFL thickness and radius of the optic nerve should be preferred to the other optic nerve MRI measures in clinical studies. Whole brain lesion and GM measures are predictive of impaired visual function with corresponding structural concomitants.

Preferred Sources of Health Information in Persons With Multiple Sclerosis: Degree of Trust and Information Sought

Background Effective health communication is important for informed decision-making, yet little is known about the range of information sources used by persons with multiple sclerosis (MS), the perceived trust in those information sources, or how this might vary according to patient characteristics. Objective We aimed to investigate the sources of health information used by persons with MS, their preferences for the source of health information, and levels of trust in those information sources. We also aimed to evaluate how these findings varied according to participant characteristics. Methods In 2011, participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry were asked about their sources of health information using selected questions adapted from the 2007 Health Information National Trends (HINTS) survey. Results Of 12,974 eligible participants, 66.18% (8586/12,974) completed the questionnaire. Mass media sources, rather than interpersonal information sources, were the first sources used by 83.22% (5953/7153) of participants for general health topics and by 68.31% (5026/7357) of participants for MS concerns. Specifically, the Internet was the first source of health information for general health issues (5332/7267, 73.40%) and MS (4369/7376, 59.23%). In a logistic regression model, younger age, less disability, and higher annual income were independently associated with increased odds of use of mass media rather than interpersonal sources of information first. The most trusted information source was a physician, with 97.94% (8318/8493) reporting that they trusted a physician some or a lot. Information sought included treatment for MS (4470/5663, 78.93%), general information about MS (3378/5405, 62.50%), paying for medical care (1096/4282, 25.59%), where to get medical care (787/4282, 18.38%), and supports for coping with MS (2775/5031, 55.16%). Nearly 40% (2998/7521) of participants had concerns about the quality of the information they gathered. Conclusions Although physicians remain the most trusted source of health information for people with MS, the Internet is the first source of health information for most of them. This has important implications for the dissemination of health information.

Reproducibility of Optical Coherence Tomography in Multiple Sclerosis

BACKGROUND Optical coherence tomography (OCT) is a promising new method of quantifying axon thickness in the retinal nerve fiber layer (RNFL) that has been used predominantly by ophthalmologists to monitor glaucoma. Optical coherence tomography is being considered as a potential outcome measure in multiple sclerosis (MS) clinical trials, but no data exist on the reproducibility of this technique in MS centers. OBJECTIVE To determine the reproducibility of OCT measurement of mean RNFL thickness in the undilated eyes of healthy control subjects and patients with MS. DESIGN Prospective analysis of 4 healthy controls to determine interrater, intrarater, and longitudinal reproducibility. Cross-sectional analysis of 3 cohorts of patients with MS (n = 396) and healthy controls (n = 153). SETTING Multiple sclerosis clinics at 3 academic medical centers. PATIENTS OR OTHER PARTICIPANTS Healthy controls and patients with MS. Main Outcome Measure Thickness of RNFL. RESULTS We found excellent agreement with respect to interrater (intraclass correlation [ICC], 0.89), intrarater (ICC, 0.98), and intervisit (ICC, 0.91) results. Mean RNFL thickness did not vary significantly among research centers for patients with MS (93, 92, and 90 microm) or among healthy controls (103, 105, and 104 microm) by site. CONCLUSIONS We demonstrate that mean RNFL thickness can be reproducibly measured by trained technicians in an MS center using the OCT-3 model. The RNFL measures from cohorts of age-matched controls and patients with MS from 3 different research centers were remarkably similar.

Impact of loss of mobility on instrumental activities of daily living and socioeconomic status in patients with MS

Abstract Objective: To assess the effects of mobility loss on instrumental activities of daily living (IADL) and socioeconomic status in multiple sclerosis (MS) patients. Methods: Participants were active registrants in the North American Research Committee on Multiple Sclerosis registry completing the Fall 2006 (IADL analysis, n = 10,396) or Spring 2007 (socioeconomic analysis, n = 8180) surveys. Cross-sectional correlations and linear and logistic regression were performed using sociodemographic factors, mobility scales, and Patient Determined Disease Steps as independent variables and IADLs as the response. Results: Mobility loss was significantly correlated with decreased IADL scores (r = −0.74; p < 0.0001); this correlation remained significant after adjustment for covariates. Mobility loss also negatively correlated with employment (r = −0.48 for women; r = −0.50 for men, both p < 0.0001) and annual income (r = −0.29; p < 0.0001). These correlations were all significant even with mild mobility loss. The relationships derived from the regression models suggest that the effect of mobility on employment is greater than the effect of demographic variables, and a small but direct effect on annual income that is independent of effects mediated through employment. The self-reported diagnosis of MS for study inclusion and use of single-item ordinal scales for mobility and disability can potentially be criticized as study limitations, although the diagnosis and the scales were previously validated. Conclusion: Mobility loss independently correlated with IADL, and associated with reduced socioeconomic status in people with MS. These correlations were significant with mild mobility loss, supporting early treatment.

Modeling Axonal Degeneration Within the Anterior Visual System: Implications for Demonstrating Neuroprotection in Multiple Sclerosis

A major objective in multiple sclerosis therapeutics is to develop strategic targeting of specific injury pathways to provide neuroprotection and potentially even restoration. Here we underscore the potential utility of the anterior visual system for the purpose of modeling neuroprotection in response to novel therapies.

Accuracy of clinical detection of INO in MS Corroboration with quantitative infrared oculography

The authors compared the accuracy of clinical detection (by 279 physician observers) of internuclear ophthalmoparesis (INO) with that of quantitative infrared oculography. For the patients with mild adduction slowing, INO was not identified by 71%. Intermediate dysconjugacy was not detected by 25% of the evaluators. In the most severe cases, INO was not identified by only 6%. Oculographic techniques significantly enhance the precision of INO detection compared to the clinical exam.

A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing-remitting multiple sclerosis

Background: Mycophenolate mofetil (MMF, CellCept®) has been utilized as an antirejection agent in transplant recipients and in patients with myriad autoimmune disorders including multiple sclerosis (MS). Objective: To investigate radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex ® at 30 mcg) in relapsing-remitting MS (RRMS). Methods: We organized a randomized, serial, 6-monthly, MRI-blinded, parallel-group multicenter pilot study to determine the safety of MMF versus interferon beta monotherapy in 35 untreated patients with RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a screening MRI of the brain. The primary outcome was the reduction in the cumulative mean number of combined active lesions (CAL), new Gd-enhancing lesions, and new T2 lesions on MRI analyses. Results: Both interferon beta and MMF appeared safe and well tolerated in the majority of patients. There was no difference between MMF therapy and the standard regimen of interferon beta therapy on the primary safety MRI endpoints of the study. However, the MMF group showed a trend toward a lower accumulation of combined active lesions, CAL, Gd and T2 lesions when compared with interferon beta treated patients. Conclusions: The results from this pilot study suggest that the application of MMF monotherapy in MS deserves further exploration.