Evaluation of the risk of cervical cancer in patients with Multiple Sclerosis treated with cytotoxic agents: A cohort study.

Background: Since most patients with relapsing-remitting multiple sclerosis (RRMS) are women, the present study aimed to determine whether treatment of patients with MS by cytotoxic agents is associated with an increased risk of cervical dysplasia. Cancer screening is often neglected in the chronic diseases such as MS, so more attention in this field was needed. Decreasing morbidity and mortality due to cervical cancer is the most important goal of screening in female MS patients especially in child bearing age. Thus, it can be said that this is the first study which investigated this important issue. Methods: A total of 129 individuals participated in this cohort study. They were assigned into 3 groups including 43 patients with MS who were treated with cytotoxic drugs, 43 patients with MS on immunomodulators, and 43 normal healthy controls. Pap smears were performed following standard methods and the results obtained from the three groups were compared by statistical analysis. Demographic data, Expanded Disability Status Scale (EDSS), and Pap smear changes were analyzed by SPSS software. Results: The most commonly detected abnormality in all examined patients and healthy controls was inflammation. Five patients with MS who were treated with cytotoxic agents revealed benign cellular changes (BCC) in their Pap smear that were statistically significant in comparison with other groups (P = 0.03). Patients who took Mitoxantrone presented BCC more than other groups [Odds ratio (OR) = 9.44, 95% confidence interval (CI): 1.46-60.70]. There was no significant difference between mean duration of MS diagnosis (P = 0.12), mean duration of previous MS treatments (P = 0.25), and mean duration of current MS treatments (P = 0.21) in patients with BCC compared to normal healthy controls or inflammatory change. Conclusion: According to the results of present study, BCC is more frequently observed in patients with MS who were treated with cytotoxic agents with immunosuppressive effect. Since BCC is a 'premalignant condition', the authors suggest that mandatory annual Pap smear should be performed for patients with MS who are treated with cytotoxic agents irrespective of their age in order to detect early signs of malignancy.

Effects of Eight-week Resistance Training Program in Men With Multiple Sclerosis.

BACKGROUND: Muscle weakness and fatigue contribute to the reduction of daily activity in multiple sclerosis (MS) patients. Therapeutic strategies to promote improvements in muscle strength and endurance are limited in individuals with MS. Some evidence showed that exercise may improve and affect different aspects of the disease including quality of life, fatigue, motor and cognitive functions. OBJECTIVES: To investigate the value of resistance training of moderate to high intensity on motor function, muscle strength, balance and perceived disability in male patients with multiple sclerosis compared to a control group. PATIENTS AND METHODS: 20 male patients with MS (mean ± SD, age: 34.05 ± 7.8 y; Expanded Disability Status Scale (EDSS): 2.94 ± 1.5) were recruited and randomized either to the exercise (E) or control group (C). Group E participated in a three-time weekly individualized progressive resistance-training program (both upper and lower extremities) for eight weeks, while group C was advised not to change their physical activity habits. All initial measures (including EDSS, balance, muscle strength, and functional mobility) were re-evaluated at the end of the program. RESULTS: Two patients of group E left the program. The other eight subjects completed the program with no MS-related exacerbations/complications. There was a significant change in 2 of 3 aspects of ambulatory function [Three minutes step test (P = 0.001), Timed Up and Go test (P = 0.009)], muscle strength (P = 0.000), and EDSS (P = 0.014). Comparing the two groups, we did not observe any significant change in "Balance" (P = 0.407). CONCLUSIONS: The resistance training of moderate to high intensity was well-tolerated in MS patients and may be an effective intervention for improving muscle strength, functional ability and EDSS-based disease severity.

Evaluation of cytokines in multiple sclerosis patients treated with mesenchymal stem cells.

BACKGROUND AND AIMS: Mesenchymal stem cells (MSC) are currently strong candidates for stem cell therapy. Cytokines have a profound effect on the resultant immune responses. This study aims to evaluate variations in the cytokine profile of multiple sclerosis patients treated with autologous MSC. METHODS: Twenty five patients received one dose of intrathecal MSCs (mean number: 29.5 × 106). To measure the gene expression of FOXP3, IFN-γ, TGF-ß, IL-4, IL-10, IL-6, and their serum proteins, samples were collected at five intervals: day 0 prior to injection and months 1, 3, 6, and 12 after MSC therapy. Gene expression was evaluated via real-time PCR and protein values were measured by ELISA. RESULTS: There were no statistically significant variations in gene expression and serum level of cytokines after a 1-year follow-up of MSC-treated MS patients. The only correlation found was an increase in IL-6 gene expression in patients with progressive disease. CONCLUSION: Intrathecal injection of MSCs does not affect cytokine variation in peripheral blood. Because the condition of most of our patients either improved or stabilized after stem cell therapy (SCT), we speculate that the immunomodulatory or neuroregenerative effects of MSC are exerted locally in the central nervous system.

Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study.

Despite updating knowledge and a growing number of medications for multiple sclerosis (MS), no definite treatment is available yet for patients suffering from progressive forms of the disease. Autologous bone marrow derived mesenchymal stem cell (BM-MSC) transplantation is a promising method proposed as a therapy for MS. Although the safety of these cells has been confirmed in hematological, cardiac and inflammatory diseases, its efficacy in MS treatment is still under study. Patients with progressive MS (expanded disability status scale score: 4.0 -6.50) unresponsive to conventional treatments were recruited for this study. Twenty-five patients [f/m: 19/6, mean age: 34.7±7] received a single intrathecal injection of ex-vivo expanded MSCs (mean dose: 29.5×10(6) cells). We observed their therapeutic response for 12 months. Associated short-term adverse events of injection consisted of transient low-grade fever, nausea /vomiting, weakness in the lower limbs and headache. No major delayed adverse effect was reported. 3 patients left the study for personal reasons. The mean (SD) expanded disability status scale (EDSS) score of 22 patients changed from 6.1 (0.6) to 6.3 (0.4). Clinical course of the disease (measured by EDSS) improved in 4, deteriorated in 6 and had no change in 12 patients. In MRI evaluation, 15 patients showed no change, whereas 6 patients showed new T2 or gadolinium enhanced lesions (1 lost to follow-up). It seems that MSC therapy can improve/stabilize the course of the disease in progressive MS in the first year after injection with no serious adverse effects. Repeating the study with a larger sample size, booster injections and longer follow-up using a controlled study design is advised.

Incidence of various cardiac arrhythmias and conduction disturbances due to high dose intravenous methylprednisolone in patients with multiple sclerosis.

BACKGROUND: High-dose intravenous methylprednisolone is the most common therapeutic modality to treat acute exacerbations in multiple sclerosis (MS). Various cardiac arrhythmias have been reported during corticosteroid pulse therapy. This study was conducted to detect cardiac rhythm changes in patients with MS while receiving high dose methylprednisolone. METHODS: We enrolled 52 consecutive MS patients with acute relapse to perform cardiac monitoring 4h before, during and 18 h after infusion of 1000 mg intravenous (IV) methylprednisolone. RESULTS: Sinus tachycardia was the most common change in cardiac rhythms before, during, and after corticosteroid pulse therapy. Up to 41.9% of the patients, developed sinus bradycardia after pulse infusion. Sinus arrest and sinus exit block were observed in 12 patients. Atrial fibrillation and ventricular tachycardia were observed in three patients and one patient, respectively. The most important cardiac arrhythmias including ventricular tachycardia, sinus arrest, and sinus exit block, were correlated with smoking and more commonly observed during 12h post infusion. Sinus bradycardia and atrial fibrillation were detected more commonly in patients with history of urinary dysfunction. CONCLUSION: High dose intravenous prednisolone might cause different types of arrhythmias in MS patients. Cigarette smokers and patients with autonomic disturbances like sphincter and bowel problems have more chance to develop arrhythmias while receiving high dose steroids.