Background It is unclear if all patients with RRMS ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration dependent. Some forms of progressive MS (e.g. PPMS) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age-of-progression-onset between SPMS and PPMS but may introduce unclear biases. Objective To confirm that onset of progressive disease course is more relevant to patient's age than the presence or duration of a pre-progression relapsing disease course in MS. Methods We studied a population-based MS cohort (n=210, relapsing-remitting MS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary- (PPMS; n=322), single attack- (SAPMS; n=112) and secondary-progressive (SPMS; n=421). We studied demographics (chi2 or t-test), age-of-progression-onset (t-test) and time-to-EDSS6 (Kaplan-Meier analyses). Results Sex-ratio (p=0.58), age-of-progression-onset (p=0.37) and time-to-EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age-of-progression-onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. Conclusions Patients with RRMS do not inevitably develop progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Human eosinophil granule major basic protein (MBP1) is an exceedingly basic (isoelectric point >11) 14-kDa protein, comprising the core of the secondary eosinophil granule. Recently, a less cationic homolog of MBP, termed MBPH or simply, MBP2, has been discovered. We prepared a panel of mAbs to MBP2 and used these Abs to localize and quantitate this molecule in leukocytes and biological fluids. Specific mAbs for MBP2 were selected using slot-blot analyses and used in a two-site immunoassay, Western blotting, and immunofluorescence microscopy. The sensitivity of the immunoassay was markedly improved by reduction and alkylation of MBP2. MBP1 is more abundant than MBP2 in lysates of eosinophils and their granules, as judged by immunoassay and Western blotting. By immunofluorescence, MBP1 is present in eosinophils, basophils, and a human mast cell line (HMC1), whereas MBP2 is only detected in eosinophils. Neither MBP1 nor MBP2 could be detected in any other peripheral blood leukocyte. MBP2 levels measured in plasma and serum were essentially identical. In contrast to past measurements for MBP1, MBP2 was not detected above normal levels in sera from pregnant donors. However, measurement of serum MBP2 discriminated patients with elevated eosinophils from normal subjects, and MBP2 was also detectable in other biological specimens, such as bronchoalveolar lavage, sputum, and stool. These results indicate that MBP2 is present only in eosinophils and that it may be a useful biomarker for eosinophil-associated diseases.

Oral ALA may improve neuropathic symptoms in diabetic DSP. A single modestly valid RCT demonstrated that 600 mg was an effective and well-tolerated dose, with NNT 2.7 to significantly reduce neuropathic pain symptoms over a 5-week period. ALA's role and place in an algorithm among other commonly prescribed oral treatments for symptomatic relief of neuropathic pain in diabetic DSP remains unclear.

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Background: Axial spondyloarthritis usually affects young people and often leads to disability. We used the interactive mobile health tool to evaluate clinical characteristics and loss of work efficiency in China, and to analyze the association between the clinical characteristics and work disability in patients with axial spondyloarthritis.Methods: In total, 1187 patients with axial spondyloarthritis were included. Demographic properties, pharmacotherapy, disease activity, functionality and spinal mobility were studied and compared in both work disability and non- work disability patients. Logistic regressions were used to investigate the associations between the risk of work disability and clinical characteristics. The relationships between Work Productivity and Activity Impairment scores and clinical characteristics were assessed using Spearman correlation coefficients. Results: Of the participants, 60 or 5.05% were unemployed. The predictive factors for the occurrence of work disability were suffering from inflammatory bowel disease, higher Physician’s global assessment and higher Assessment of Spondyloarthritis International Society health index (ASASHI) scores (OR value was 3.35, 1.32 and 1.45 respectively). Absenteeism, presenteeism, overall work impairment and activity impairment in all employed patients were 10.40%, 23.53%, 30.57% and 25.35% respectively. Factors significantly associated with higher presenteeism, overall work impairment and activity impairment loss were Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, ASASHI, nocturnal pain, total back pain, and Patient’s global assessment (r >0.5), while non-steroidal anti-inflammatory drugs treatment were significantly associated with a lower absenteeism loss. An increased ASDAS score was related to a decrease in work productivity.Conclusions: We used a Smart-Phone Management System to determine that axial spondyloarthritis had a significant influence on working conditions in China, and that the factors related to the disease had a significant correlation with the risk and severity of lost work productivity. SpAMS is found be a time- and cost-saving disease management tool which can help patients with AS independently manage their disease and provide valuable data to their clinicians.

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Dalfampridine is a potassium-channel blocker that is approved by the US FDA as 10 mg extended-release tablets to improve walking in patients with multiple sclerosis. Approval is currently pending in Europe. This is the first pharmacological symptomatic treatment approved for multiple sclerosis patients of any type with walking difficulties. Relative to an immediate-release formulation, the extended-release formulation of dalfampridine lowers peak serum concentrations that contribute to toxicity while maintaining a comparable amount of total drug exposure. Several studies show the efficacy and tolerability of dalfampridine. The pivotal published clinical trial demonstrated a treatment–responder rate of 35% compared with an 8% placebo–responder rate (p < 0.0001). The subjects who responded to treatment had an average improvement in their 25-foot walking test time of 25.2% (95% CI: 21.5–28.8) compared with an average improvement of 4.7% (95% CI: 1.0–8.4) in subjects who responded to placebo. Seizures are the most serious adverse effect of dalfampridine with a probable dose-dependent likelihood of occurrence.