Gabriel Pardo

Background Eighty-five percent of people with multiple sclerosis (MS) incur gait impairments debilitating enough to significantly impact their function. Objectives The aim of this study was to determine if a novel combination of intermuscular electrical stimulation, followed by functional electrical stimulation combined with supported bodyweight treadmill training, would improve gait, decrease spasticity and fatigue, and improve muscle strength. Methods Using a pre-post experimental design, we implemented this combination six-week protocol in 16 individuals with MS. We completed summary statistics and longitudinal pre-post results using Wilcoxon sign rank tests with Bonferroni adjustment. Results Participants responded with median increases of 29.4 feet ( p 

Objective: To assess the safety/tolerability of opicinumab vs. placebo in participants with relapsing multiple sclerosis (MS) when used chronically and concurrently with interferon (IFN) beta-1a. Background: Opicinumab (anti-LINGO-1; BIIB033) is a human monoclonal antibody candidate MS reparative agent that blocks LINGO-1, a CNS-specific negative regulator of myelination and neuroaxonal regeneration. Design/Methods: SYNERGY (NCT01864148) was a randomized, multicenter, double-blind, placebo-controlled study. Eligible participants were aged 18–58 years with a diagnosis of relapsing-remitting (RRMS) or secondary progressive MS (SPMS) and disease activity in the previous year. Disease activity for RRMS was defined as ≥2 distinct episodes of: clinical relapse, gadolinium-positive (Gd+) lesion or new T2 lesion on brain/spinal cord MRI; for SPMS it was ≥1 occurrences of clinical relapse or Gd+ lesion on brain/spinal cord MRI. Participants were randomized to 3, 10, 30 or 100 mg/kg opicinuma...

The CHORDS trial evaluated ocrelizumab (OCR) in patients with relapsing‐remitting multiple sclerosis who had a suboptimal response to previous disease‐modifying treatment. The objective of the present study was to assess the safety of shorter OCR infusions in a substudy of CHORDS. After completing four doses of OCR per initial US prescribing recommendations in the main study, participants in the substudy (N = 129) received a fifth dose over a 2‐h duration (vs. 3.5 h). Infusion‐related reactions occurred in 12.4% of patients. None were severe, life‐threatening or led to treatment discontinuation. Shorter infusion time did not change the safety profile of OCR. Clinicaltrials.gov (NCT0237856).

The acute and chronic effects of whole-body vibration (WBV) on balance, postural stability, and mobility were evaluated in 21 women with relapsing-remitting multiple sclerosis (MS) randomly assigned to control (n = 9) or experimental (n = 12) groups. To assess acute responses, outcome variables were assessed before and immediately after a session of WBV (five 30-second bouts of vibration; frequency 30 Hz; amplitude 3 mm; 1-minute rest intervals) during their first visit (week 1) using field (Timed-Up and Go; 500-m walk; Berg Balance Scale) and laboratory tests (NeuroCom Balance Master and EquiTest System—Sensory Organization Test, Adaptation Test, Limits of Stability, Modified Clinical Test for Sensory Integration of Balance, Unilateral Stance, Tandem Walk, Step/Quick Turn). Acute responses were also measured after their fifth visit for only the Adaptation and Sensory Organization tests. For the chronic responses, participants were exposed to the WBV protocol once a week, for a tota...

Background In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing–remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656). Methods In CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course. In the open-label, nonrandomized extensions, patients could receive as-needed additional alemtuzumab or other disease-modifying therapies. Results Of 108 alemtuzumab-treated patients in CAMMS223, 60 entered the CAMMS03409 extension; 33% received a total of 2 alemtuzumab courses, and 73% received no more than 3 courses through Year 12. Over 12 years, annualized relapse rate was 0.09, 71% of patients ha...

A prospective, randomized, three-arm, evaluator blinded study to demonstrate the feasibility of a telerehabilitation (TR) program in individuals with ambulatory deficits secondary to Multiple Sclerosis (MS) and evaluate its efficacy when compared to conventional on-site physical therapy (PT) was completed. Thirty participants were evaluated at baseline and randomized to one of three groups with intervention lasting 8 weeks: Group 1 (control)- customized unsupervised home-based exercise program (HEP) 5 days a week; Group 2 (TR)- remote PT supervised via audio/visual real-time telecommunication twice weekly; Group 3 (PT)- in-person PT at the medical facility twice weekly. Outcomes included patient reported outcomes (PROs) obtained through questionnaires, and measurements of gait and balance performed with bedside tests and a computerized system. Functional gait assessment improved from baseline in all three groups. There were no significant differences between the TR and the conventio...

Objective To review instruments used to assess disease stability or progression in persons with multiple sclerosis (pwMS) that can guide clinicians in optimizing therapy. Methods A non-systematic review of scientific literature was undertaken to explore modalities of monitoring symptoms and the disease evolution of MS. Results Multiple outcome measures, or tools, have been developed for use in MS research as well as for the clinical management of pwMS. Beginning with the Expanded Disability Status Scale, introduced in 1983, clinicians and researchers have developed monitoring modalities to assess all aspects of MS and the neurological impairment it causes. Conclusions Much progress has been made in recent decades for the management of MS and for the evaluation of disease progression. New technology, such as wearable sensors, will provide new opportunities to better understand changes in function, dexterity, and cognition. Essential work over the decades since EDSS was introduced con...

Lower limb asymmetries have been observed in persons with multiple sclerosis (PwMS), and have been associated with mobility impairment. An incremental cycling test was performed on a cycle ergometer to determine peak power output (PPO) and peak oxygen consumption (VO2peak). Then, participants cycled at 50%, 60%, and 70% of their PPO to assess the contribution of each lower limb to power production. Two-way repeated measures ANOVA was used to detect group × intensity differences in power production asymmetry. Eight PwMS and six healthy individuals (Non-MS) completed the study. No statistically significant (p > 0.05) group × intensity interactions or main effects were present when examining between-limb differences in power production. The current data do not indicate a statistically significant difference in power production asymmetry between groups and exercise intensities. Previous research has established a 10% difference between contralateral limbs as a threshold for asymmetry...

Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18-58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0-6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by ...

The treatment landscape for relapsing forms of multiple sclerosis (RMS) has expanded considerably over the last 10 years with the approval of multiple new disease-modifying therapies (DMTs), and others in late-stage clinical development. All DMTs for RMS are believed to reduce central nervous system immune-mediated inflammatory processes, which translate into demonstrable improvement in clinical and radiologic outcomes. However, some DMTs are associated with long-lasting effects on the immune system and/or serious adverse events, both of which may complicate the use of subsequent therapies. When customizing a treatment program, a benefit-risk assessment must consider multiple factors, including the efficacy of the DMT to reduce disease activity, the short- and long-term safety and immunologic profiles of each DMT, the criteria used to define switching treatment, and the risk tolerance of each patient. A comprehensive benefit-risk assessment can only be achieved by evaluating the imm...

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 co...

Nausea, vomiting, diarrhea, headache and myalgias for five days with later development of diplopia and oscillopsia. A 39 year-old Caucasian female. She was found to have a large angle exotropia, limitation of abduction, adduction and infraduction OD and limitation of adduction OS. Decadron, Doxycycline, Acyclovir no

The syndrome characterized by papillomacular bundle damage, central or cecocentral scotoma, and reduction of color vision can be produced by toxic, nutritional, or hereditary causes. Patients who present with such a picture should be evaluated for toxic sources such as tobacco or alcohol use. Nutritional deficiencies must be considered and a good family history should be obtained to explore hereditary factors. DNA mutation analysis is available to detect genetic abnormalities. A trial of nutritional replacement may be advisable even in the face of normal laboratory values. Previous reports have shown dramatic visual improvement with intramuscular hydroxocobalamin and other oral vitamin B complexes, even when specific deficiencies are not found.

RNF (Rebif New Formulation, Merck Serono International S.A., Geneva, Switzerland), a formulation of interferon-beta1a (IFN-beta1a) without human- or animal-derived components, is currently under investigation. It was developed with the aim of maximizing the treatment benefit for patients with multiple sclerosis (MS) by improving injection tolerability and reducing the development of neutralizing antibodies (NAbs). This paper reports the results of planned 24- and 48-week interim analyses comparing immunogenicity and tolerability data from an ongoing study of RNF with historical-control data for the currently approved formulation of IFN-beta1a from the EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study. Patients in the 96-week, multicenter, singlearm, Phase IIIb RNF study received 44 microg/0.5 mL SC tiw; patients in the EVIDENCE study received an identical regimen of the currently approved formulation of IFN-beta1a. Criteria for inclusion in the RNF study were age between 18 and 60 years, an Expanded Disability Status Scale (EDSS) score <6.0, and a diagnosis of relapsing MS (McDonald criteria). Criteria for inclusion in the EVIDENCE study were age between 18 and 55 years, an EDSS score of 0 to 5.5, and a diagnosis of clinically definite relapsing-remitting MS (Poser criteria). Patients in both studies were treatment naive. Both studies used the same cytopathic-effect assay for NAbs to assess immunogenicity; patients who had NAb titers >or=20 neutralizing units (NU)/mL were considered NAb+. The primary end point was to compare the proportions of NAb+ patients in the RNF study and the historical data. Comparisons were descriptive and used exact 95% CIs. Safety analyses included 8 prespecified adverse events (AEs) of interest. Baseline demographic characteristics were well balanced between the RNF (N = 260) and EVIDENCE (N = 339) studies, except that patients in the RNF study were slightly younger (median age, 34.0 vs 39.0 years, respectively), and a few had secondary progressive MS (n = 6) or progressive relapsing MS (n = 1). At week 48, 87.3% of patients in the RNF study remained on treatment. The incidence of the prespecified AEs of interest in the RNF and EVIDENCE studies was as follows: flu-like symptoms (70.8% and 48.1%, respectively), injection-site reactions (29.6% and 83.8%), hepatic disorders (13.1% and 16.8%), cytopenia (9.6% and 11.8%), depression and suicidal ideation (5.8% and 19.8%), skin rashes (5.4% and 12.1%), hypersensitivity reactions (5.4% and 3.2%), and thyroid disorders (2.3% and 5.0%). Overall, the majority (96.9%) of AEs in the RNF study were mild (69.5%) or moderate (27.5%) in severity. The proportions of patients in the RNF and EVIDENCE studies with NAbs at both 24 and 48 weeks were 2.5% (95% CI, 0.9-5.5) and 14.3% (95% CI, 10.7-18.6), respectively; the proportions with NAbs at week 48 only were 13.9% (95% CI, 9.9-18.7) and 24.4% (95% CI, 19.9-29.4). The proportions of NAb+ patients with high NAb titers (>1000 NU/mL) at week 48 were 11.1% in the RNF study and 19.5% in the EVIDENCE study. The results of these interim analyses suggest that RNF had an improved overall tolerability and safety profile and a lower immunogenic potential compared with the approved IFN-beta1a formulation assessed in the EVIDENCE study. Two-year results from the RNF study are anticipated before the end of 2007.

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. 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. 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. 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.

Background Thermo sensitivity (TS), characterized by worsening of neurological symptoms due to increased body temperature, is com-mon in individuals with multiple sclerosis (MS). Fatigue is also a common complaint. Both TS and fatigue can lead to decreased participation in physical activity (PA) in this population. Purpose The primary purpose of this study was to determine through self-report if TS and fatigue have any effect of PA levels in indi-viduals diagnosed with MS. Methods Seventy seven men and women between the ages of 22 and 69 with a diagnosis of Multiple Sclerosis according to McDonald criteria participated in this study (μ = 45.2 ± 1.4). Physical activity level was measured by Godin Leisure-Time Exercise Question-naire, and fatigue by the Fatigue Severity Scale (FSS). TS was recorded by self-report. Results Eighty-three percent of the group reported TS (91.8% of females and 65.2% of males). Individuals that reported TS participated significantly less in physical activit...

ABSTRACT Antiphospholipid syndrome may be primary or secondary to various autoimmune processes or infection. Neurologic symptoms may result from vascular thrombosis or direct damage to neurons, glial cells and myelin. We report a patient who initially presented with neurologic symptoms, including ophthalmoplegia, and normal brainstem neuroimaging. An underlying infectious endocarditis and antiphospholipid syndrome were not diagnosed until late in the course of her disease.

Patients with multiple sclerosis often use injectable medication such as glatiramer acetate or interferons to treat their disease. Subcutaneous injections may be associated with local injection site reactions (LISRs), which can include itching, pain, swelling, or redness. Although not serious, these side effects are bothersome and can have a negative impact on adherence to the therapeutic regimen, particularly in early phases of treatment. This randomized parallel group study of 83 patients with multiple sclerosis who had recently begun glatiramer acetate therapy investigated whether administration of an oral antihistamine (cetirizine hydrochloride; Zyrtec, 10 mg) prior to each daily subcutaneous injection of glatiramer acetate would lower the incidence of LISRs compared with an oral placebo. Data for the outcome measures were derived from patient diaries and from the clinic during the baseline and the treatment periods. The primary outcome measure comparing the number of LISRs at 5 minutes after injection over 2 weeks was slightly but not significantly lower in patients who received cetirizine compared with patients who received placebo. Within-group comparisons showed that there was a significant reduction in mean LISR score from the 2-week baseline period to the 2-week cetirizine treatment period (0, 2, and 5 minutes after treatment). Both groups showed decreases in the average bothersome ratings from the baseline to treatment periods. Use of cetirizine did not affect the type of LISRs that was reported at any time point. There were no safety concerns with the concurrent administration of cetirizine with glatiramer acetate. Because there were no statistically significant differences on the primary end point between patient groups taking cetirizine and those taking placebo prior to glatiramer acetate injections, cetirizine use as a strategy to reduce LISRs in patients on glatiramer acetate therapy cannot be recommended at this time.