Staphylococcus aureus harbouring Enterotoxin A as a possible risk factor for multiple sclerosis exacerbations.

BACKGROUND: Staphylococcus aureus may produce superantigens that can non-specifically activate CD4(+) cells to potentially target the myelin basic protein. OBJECTIVE: This study examined the association between individuals with multiple sclerosis (MS) and colonization with S. aureus harbouring superantigens. METHODS: Nasal swabs were collected from non-MS subjects and patients with MS who had not experienced a relapse in the past six months (MS stable group) and who had suffered a relapse within 30 days of study recruitment (MS exacerbation group). S. aureus was isolated from the anterior nares of participants following standard procedures and staphylococcal superantigen genes (sea, seb, and tsst-1) were detected using standard laboratory PCR techniques. RESULTS: The study enrolled 204 patients, 80 in the non-MS and MS stable groups and 44 patients in the MS exacerbation group. Overall, 27.0% of patients were colonized with S. aureus with no significant differences identified between study groups. Amongst individuals colonized with S. aureus, the prevalence of sea was significantly greater in the MS exacerbation versus non-MS study group (p < 0.05; odds ratio 7.9; 95% confidence interval 1.2-49.5). CONCLUSIONS: The ability to rapidly screen patients for the presence of S. aureus producing sea may serve as a useful marker of a potential MS exacerbation.

Fatigue and cognition in patients with relapsing multiple sclerosis treated with interferon ß.

INTRODUCTION: Fatigue and cognitive deficits are common symptoms affecting patients with multiple sclerosis. METHODS: The effects of interferon beta on fatigue and cognitive deficits were assessed in 50 patients with relapsing multiple sclerosis (recruited at a single center). The pre-treatment assessments were performed on visits 1 and 2 (Months 0 and 3). Patients started treatment with subcutaneous interferon beta-1a or beta-1b, or intramuscular interferon beta-1a at Month 3, with reassessment at visits 3 and 4 (6 and 12 months, respectively). Co-primary endpoints were change in fatigue (Modified Fatigue Impact Scale) and change in cognition (Brief Repeatable Battery of Neuropsychological Tests) from pre-treatment to visits 3 and 4. Follow-up data were obtained for 40 patients. RESULTS: The pre-treatment demographic and disease characteristics did not differ between groups. Improvements in fatigue levels were reported for patients receiving subcutaneous interferon beta-1a versus patients in the intramuscular interferon beta-1a group (p = .04) and in the interferon beta-1b group (p = .09). Improvements were also reported in five out of 17 cognitive indices for all the treatment groups. CONCLUSION: The data suggest that interferon beta may reduce fatigue and cognitive deficits in patients with relapsing multiple sclerosis. Larger, randomized, and controlled studies are required to confirm our findings.

A treatment algorithm for neuropathic pain: an update.

OBJECTIVE: The purpose of this review is to provide an update of the neuropathic pain treatment algorithm previously published by Namaka et al. in 2004. This algorithm focuses on the strategic incorporation of the latest pain therapies while providing an update of any recent developments involving medications previously listed in the algorithm. DATA SOURCES: PubMed, MEDLINE, Cochrane, and Toxnet databases were used to conduct all literature searches on neuropathic pain and targeted treatment strategies. Comprehensive search efforts in the identified databases included studies published between 1980 and 2009. The search term "neuropathic pain" was used along with each of the agents outlined in this review: pregabalin, paroxetine CR, duloxetine, tramadol XL, Tramacet, Sativex, and nabilone. STUDY SELECTION: A total of 90 studies were reviewed and selected based on level 1, 2, and 3 search strategies. DATA EXTRACTION: Level 1 search strategies were initially aimed at evidence-based trials of large sample size (N > 100), with a randomized, double-blind, placebo-controlled design conducted by investigators well versed in the specialty area of interest. A level 2 search was conducted for additional trials that had many, but not all, of the desirable traits of evidence-based trials. In addition, a level 3 search strategy was conducted to compare key findings stated in anecdotal reports of very small (N < 15), poorly designed trials with the results of well-designed, evidence-based trials identified in level 1 and/or level 2 searches. DATA SYNTHESIS: Based on a thorough evaluation of the literature, pregabalin, paroxetine CR, and duloxetine have been placed in the updated algorithm as first-line agents, while tramadol XL, Tramacet, Sativex, and nabilone function primarily as adjunctive agents. CONCLUSION: The updated algorithm provides a baseline framework from which clinicians can justify the medication they prescribe.

Examining the evidence: complementary adjunctive therapies for multiple sclerosis.

OBJECTIVE: The purpose of this article is to provide a comprehensive overview of the most frequently encountered non-conventional approaches trialed for use in multiple sclerosis (MS). The efficacy and safety of non-conventional approaches ranging from bee venom therapy (BVT) to an array of vitamins and herbal products were discussed and evaluated. METHODS: Relevant English-language articles were identified through searches of MEDLINE (1990-2006), PubMed (1999-2006), Cochrane (1995-2006) and Toxnet (2000-2006). Classification of available literature was conducted according to the evidence based guidelines established by the American Academy of Neurology (AAN). However, due to the non-conventional nature of these treatment approaches, most available literature was derived from anecdotal reports and suboptimal clinical studies, lacking the rigor of evidence-based practice. RESULTS: There is presently only marginal supportive evidence for BVT in MS treatment. The inability to identify and quantify the active component of BVT combined with the associated risk of anaphylaxis has deterred its widespread use. The most promising evidence comes from prophylactic daily supplementation with vitamin D. Despite beneficial reports regarding non-herbal supplements such as alpha-lipoic acid (ALA), luteolin, evening primrose oil and vitamins such as B12, the lack of evidence does not support their prophylactic use. DISCUSSION: Based on available evidence, the prophylactic use of vitamin D is a viable option as an adjunct to conventional medicine. Although there is a lack of conclusive evidence to support the use of other non-conventional treatments, patients are still opting to trial and bare the risks of these products which are accessible without the intervention of a healthcare professional. Controlled, evidence-based trials are essential for healthcare professionals to competently intervene and recommend these products.

Axotomy-induced up-regulation of tumor necrosis factor-alpha in the dorsal root ganglia.

OBJECTIVES: Neuropathic pain is a chronic pain syndrome associated with drug, injury or disease-induced damage or destruction of sensory afferent fibers of the dorsal root ganglia (DRG). Although the exact underlying pathologic mechanisms are not known, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) are recognized as potential modulators of peripheral and central nervous system inflammatory responses. They play a crucial role in injury and the pathologic development of chronic pain syndromes such as neuropathic pain. METHODS: Twenty-four rats were divided into a naive control (n=6), sham (surgery exposing sciatic nerve, n=6), and peripheral nerve lesion group (unilateral axotomy of sciatic nerve, n=12). RESULTS: The results of this study demonstrate a transient up-regulation of TNF-alpha expression within ipsi- and contralateral DRG following complete unilateral sciatic nerve axotomy as confirmed by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR. Elevated expression of TNF-alpha was noted to occur within the first 7 days post-axotomy, which subsequently normalized to baseline levels by day 14. This transient up-regulation was also associated with a switch in cellular source from predominant satellite cell expression at baseline to that involving satellite cells and abundant numbers of sensory neurons. DISCUSSION: These results support the role of TNF-alpha in the upstream cascade of cellular events involved in the underlying pathogenesis of neuropathic pain. Strategies targeting the early attenuation of TNF-alpha within the DRG during the first week post-injury may have significant clinical impact in preventing the downstream cascade of events involved in the underlying cellular pathology of neuropathic pain.

The clinical importance of neutralizing antibodies in relapsing-remitting multiple sclerosis.

BACKGROUND: Neutralizing antibodies (NAbs) develop in patients receiving interferon beta (IFN-beta) for multiple sclerosis (MS). Debate continues concerning the relevance of NAb development on treatment efficacy. OBJECTIVE: To determine the incidence and clinical importance of NAbs in patients with relapsing-remitting MS (RRMS). METHODS: A comprehensive literature review was conducted using PubMed (accessed from 1983 to June 2005), Cochrane MS Group trials register (accessed June 2005), MEDLINE (accessed 1983 to June 2005), and Toxnet (accessed June 2005) databases. NAb-induced changes in clinical efficacy and disease progression were evaluated according to the clinical guidelines established by the American Academy of Neurology. RESULTS: Currently, there is no standardized assay to comparatively assess NAbs among different treatments. NAbs develop independent of age, sex, disease duration and progression index at the onset of treatment. The occurrence of NAbs varies from 2-45% depending on the treatment initiated. NAb+ patients demonstrate accelerated disease progression as confirmed by an approximate 1-point increase in the Expanded Disability Status Scale score. The odds of relapse during a NAb+ period are between 1.51 and 1.58 (p < 0.03) with the time to first relapse being shortened by an average of 244 days after 12 months of IFN-beta therapy. NAb+ patients experience an approximately four-fold increase (p = 0.009) in the median number of active T2 magnetic resonance imaging (MRI) lesions compared to NAb-negative patients (1.4 vs. 0.3 respectively, p < 0.01). CONCLUSION: The induction of NAbs in IFN-beta treated patients reduce clinical effect and accelerate disease progression.