Thalamic asymmetry in Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic neuroinflammatory disease that affects the central nervous system. Asymmetry is one of the finding in brain MRI of these patients, which is related to the debilitating symptoms of the disease. This study aimed to investigate and compare the thalamic asymmetry in MS patients and its relationship with other MRI and clinical findings of these patients. METHODS: This cross-sectional study conducted on 83 patients with relapse-remitting MS (RRMS), 43 patients with secondary progressive MS (SPMS), and 89 healthy controls. The volumes of total intracranial, total gray matter, total white matter, lesions, thalamus, and also the thalamic asymmetry indices were calculated. The 9-hole peg test (9-HPT) and Expanded Disability Status Scale (EDSS) were assessed as clinical findings. RESULTS: We showed that the normalized whole thalamic volume in healthy subjects was higher than MS patients (both RRMS and SPMS). Thalamic asymmetry index (TAI) was significantly different between RRMS patients and SPMS patients (p = 0.011). The absolute value of TAI was significantly lower in healthy subjects than in RRMS (p < 0.001) and SPMS patients (p < 0.001), and SPMS patients had a higher absolute TAI compared to RRMS patients (p = 0.037). CONCLUSIONS: In this cross-sectional study we showed a relationship between normalized whole thalamic volume and MS subtype. Also, we showed that the asymmetric indices of the thalamus can be related to the progression of the disease. Eventually, we showed that thalamic asymmetry can be related to the disease progression and subtype changes in MS.

Effects of Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Stress Reduction (MBSR) on symptoms and emotional competencies in individuals with multiple sclerosis.

BACKGROUND: Compared to the general population, individuals with multiple sclerosis (MS) report higher levels of insomnia, depression, fatigue, and paresthesia, and lower levels of emotional competencies (understanding emotions in self and others). Available treatments are limited, and novel approaches to reducing symptoms and enhancing emotional competencies in MS are needed. Two potentially beneficial treatments are Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Stress Reduction (MBSR). The aim of the present study was to investigate the impact of ACT and MBSR on symptoms and emotional competencies in patients with MS. METHODS: A total of 76 individuals with MS (81.6% females; mean age: 38.88 years; EDSS median: 2; range: 0-5) were randomly assigned to an 8-week ACT treatment, an 8-week MBSR treatment, or a wait-list control condition. At baseline and study-end (week 8), participants completed a series of questionnaires covering symptoms and emotional competencies. At mid-term (week 4), participants rated their insomnia and depression. RESULTS: Over time, symptoms of MS decreased (medium effect size for insomnia, fatigue, and paresthesia, and large effect size for depression) and emotional competencies improved (large effect size), but more so in the MBSR and ACT conditions, compared with the control condition. At study-end, the outcome improvement did not differ between the ACT and MBSR conditions. CONCLUSIONS: Both ACT and MBSR led to reduced symptoms and enhanced emotional competencies. Psychotherapeutic interventions such as these should be considered as a means of decreasing symptoms and increasing emotional competencies among individuals with MS.

The Role of Cobalamin on Interleukin 10, Osteopontin, and Related MicroRNAs in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Considering how vitamin B12 or cobalamin affects the immune system, especially inflammation and the formation of the myelin sheath, it appears as a complementary therapy for MS by affecting some signaling pathways. Recently diagnosed MS patients were divided into two groups (n=30). One group received interferon-beta (IFN-ß or Avonex), and another received IFN-ß+B12 for six months. Blood samples were taken before and after treatments.  Interleukin (IL)-10 and osteopontin (OPN) levels in the plasma were determined by the enzyme-linked immunosorbent assay (ELISA) method, and the expression of microRNA (miR)-106a, miR-299a, and miR-146a by real-time PCR. IFN-ß neither changed the IL-10 plasma levels nor miR106a and miR-299a expression, but it led to a remarkable decrease in OPN concentration and enhancement in let-7c and miR-146a expression. There was a significant decrease in IL-10, OPN plasma levels, miR-106a expression, and a substantial increase in let-7c and  miR-146a expression in IFN-ß+B12, treated group. There was no correlation between IL-10 and OPN with related miRNAs in the two treatment groups. Our study indicated that B12 could be a complementary treatment in MS that may influence the disease improvement.

Mizaj assessment in Multiple Sclerosis (MS) patients based on Persian Medicine.

OBJECTIVES: Increased incidence of Multiple Sclerosis (MS) calls for supporting complementary therapies in this field. Persian Medicine (PM) specialists present various assumptions to help patients through Mizaj (temperament) modification, but its confirmation requires scientific evidence. This study aimed at identifying the Mizaj of MS patients, and comparing it with their Mizaj before the onset of the disease, and with that of healthy people. METHODS: Forty-two MS and fifty-four healthy subjects participated in the study as case and control groups. General and brain Mizaj in patients were identified by five PM specialists before and after the onset of the disease. Mojahedi Mizaj Questionnaire (MMQ) was completed by the two groups. The validity of MMQ was assessed using Mizaj diagnosis by PM specialists as the gold standard. T-test, McNemar-Bowker, Wilcoxon, and Chi-square (χ 2) tests were used to compare the Mizaj of patients before and after the onset of the disease, and between the two groups (p<0.05). RESULTS: The sensitivity and specificity of MMQ for Hotness (75, 81%) and Coldness (75, 65%) were acceptable. There were no significant differences between patients and healthy subjects in terms of general Mizaj. But general and brain Mizaj of patients after developing MS inclined to coldness and dryness, although merely inclination of general Mizaj to coldness was significant (p=0.03). CONCLUSIONS: According to our results, the Mizaj of MS patients has an inclination toward coldness and dryness; Also, MMQ can be used as a validated scale for identifying the Mizaj of MS patients in future studies.

The Effect of Emotional Freedom Technique on Fatigue among Women with Multiple Sclerosis: A Randomized Controlled Trial.

BACKGROUND: This study aimed to investigate the effect of Emotional Freedom Technique (EFT) on the severity of fatigue among women with Multiple Sclerosis (MS). MATERIALS AND METHODS: This was a single-blind, randomized controlled trial study conducted on 50 women with MS in Isfahan, Iran. Sampling was performed using simple sampling method, then the participants were randomly divided into two groups of case and sham using the minimization method. The EFT intervention was performed on the case group, 2 sessions per week for a 4-weeks period. In the sham group, with the same psychological part of the EFT technique like case group, mild tapping was applied on false points for the same period of time. Fatigue severity score was obtained using the Fatigue Severity Scale (FSS) before and immediately and 4 weeks after the intervention in the two groups. Data analysis was conducted using descriptive and inferential statistical methods. RESULTS: The results of the independent t-test indicated that the mean (SD) score of fatigue severity before the intervention was not significantly different between the case and sham groups 5.48 (0.75) and (5.39 (0.71) with (p = 0.67). However, this difference was significant immediately [(3.05 (0.89) and 5.15 (0.94)] and 4 weeks after the intervention 3.10 (0.81) and 5.59 (0.57) (p < 0.001). CONCLUSIONS: It seems that EFT is effective in diminishing fatigue among patients with MS and is recommended as a convenient and safe non-medicament strategy for self-management of fatigue among these patients, and can be used at the bedside by nurses.

Silymarin Restores Regulatory T Cells (Tregs) Function in Multiple Sclerosis (MS) Patients In Vitro.

Dysregulation of the immune system and impairment in the function and number of patient-derived regulatory T cells (Treg) have an important role in multiple sclerosis (MS) pathogenesis. MS patients still receive different medications to overcome the relapses and to slow the disease progression. However, the benefits of these therapies are limited and are accompanied by different side effects. The immunoregulatory effects of Silymarin as a plant-derived flavonoid have shown in studies. In the present study, regulatory T cells (Tregs) were isolated from MS patients who diagnosed as new cases and IFN-ß-treated RRMS patients. Isolated Treg cells were cultured in the presence of different concentrations of Silymarin (50, 100, 150 µM) for 48, 72, and 120 h. Proliferation and activation of Treg cells were assessed by flow cytometry. Also, FOXP3, JAK3, and STAT5 gene expression, IL-10, and TGF-ß production by Tregs were evaluated by real-time PCR and ELISA respectively. The results showed that Silymarin promoted Treg proliferation at 100 µM concentration after 72 h. Additionally, IL-10, TGF-ß levels, and FOXP3, JAK3, and STAT5 gene expression enhanced by Silymarin dose and time dependently. Our preliminary results suggest that the induction and activation of Tregs could be an underlying mechanism of the ancient used herbal medicine Silymarin, providing effective means against autoimmune and inflammatory diseases.

Evaluation of glucose-6-phosphate dehydrogenase serum level in patients with multiple sclerosis and neuromyelitis optica.

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are both demyelinating disorders and oxidative stress is suggested to have a role in their pathogenesis. Glucose-6-phosphate dehydrogenase (G6PD) produces nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. NADPH is not only involved in the synthesis of fatty acids necessary for myelination, but also it is involved in the defense against oxidative stress. Prescribing supplementary vitamin D as a part of the MS treatment plan can increase G6PD gene expression. The aim of this study was to determine the serum level of G6PD in patients with MS and NMO and its relationship with vitamin D, since it is yet to be explored thoroughly. Methods: In this case-control study, subjects were divided into three experimental and control groups. The experimental groups comprised 50 patients with relapsing-remitting MS (RRMS) who had a history of vitamin D consumption, 50 newly-diagnosed MS patients, and 50 patients with NMO. Control group included 65 healthy individuals. Serum level of G6PD was measured and compared among these groups. Results: No significant difference was seen between the G6PD level in patients with MS and NMO, but it should be noted that this level was significantly lower than the healthy group. G6PD serum level was significantly higher in patients with MS who had previously consumed supplementary vitamin D compared to those who had not. Conclusion: G6PD deficiency is observed in patients with MS and NMO. Also, supplementary vitamin D may induce favorable results on the G6PD level.

Immunoregulatory Effects of Silymarin on Proliferation and Activation of Th1 Cells Isolated from Newly Diagnosed and IFN-ß1b-Treated MS Patients.

Multiple sclerosis (MS) is a central nervous system autoimmune disease characterized by demyelination. Autoreactive T cells mainly interferon gamma (IFN-γ) producing T helper cells (Th1) have an important role in MS pathogenesis. Silymarin is a unique blend produced from milk thistle (Silybum marianum) plant which its imunomodulatory role has been indicated in studies. In the present study, the effects of silymarin on isolated Th1 cells were investigated in newly diagnosed MS patients and those who received betaferon. PBMCs were separated from newly diagnosed and IFN-ß-treated MS patients. The Th1 cell isolation from PBMCs was performed using a human Th1 cell isolation kit. Th1 cells were cultured in the presence of silymarin (50, 100, and 150 µM for 48, 72, and 120 h). Th1 cell proliferation and CD69 expression were assessed by flow cytometry. Also, IFN-γ production and T-bet gene expression were measured by ELISA and real-time PCR respectively. In vitro cultured Th1 cells showed that silymarin suppresses Th1 cell proliferation dose and time dependently in newly diagnosed and IFN-ß-treated MS patients in comparison to DMSO control. Also, CD69 expression as an early activation marker was changed after Th1 cell treatment with different doses of silymarin at different times. T-bet gene expression was significantly decreased in Th1 cells isolated from newly diagnosed and IFN-ß-treated RRMS patients after treatment with silymarin compared to DMSO control. Additionally, IFN-γ production by Th1 cells was decreased after treatment silymarin in newly diagnosed patients; however, in IFN-ß treated after 48-h treatment with silymarin, IFN-γ concentration was decreased at concentrations of 100 and 150 µM, and after 120 h, a significant increase was observed in the IFN-γ level at a concentration of 100 µM in comparison with DMSO. Our findings here clearly show that silymarin is an effective regulator for Th1 response in vitro condition. It not only suppresses Th1 proliferating activity but also inhibits T-bet gene expression and IFN-γ production by these cells.

Evaluating the effect of adding Fish oil to Fingolimod on TNF-α, IL1ß, IL6, and IFN-γ in patients with relapsing-remitting multiple sclerosis: A double-blind randomized placebo-controlled trial.

OBJECTIVES: Fish oil is claimed to improve outcome in multiple sclerosis (MS) through anti-inflammatory and antioxidant effects by reducing cytokines including TNF-α, IFN-γ, IL6, and IL-1ß. We aimed to evaluate the efficacy of adding fish oil to Fingolimod on these serum cytokines. PATIENTS AND METHODS: This double-blind randomized trial was conducted during April 2015 to September 2016 in Isfahan, Iran. Patients with diagnosis of relapsing remitting MS, aged 18-45years old and expanded disability status scale (EDSS) ≤5 were enrolled in the study. The experimental group received 1g/day of fish oil. Serum levels of TNF-α, IFN-γ, IL6, and IL-1ß were measured before intervention, 6 months, and 12 months after intervention as the primary outcome. Also, EDSS was evaluated before and at the end of study. RESULTS: 50 patients were recruited initially and nine of them left the study. We found no difference between serum levels of TNF-α, IFN-γ, IL6, and IL-1ß at three time-points between two groups (P-value >0.05). Also, there was no statistically significant difference in the mean EDSS between the experimental group and the control group after 12 months of intervention (P-value=0.08). CONCLUSIONS: Administration of fish oil did not lower the serum levels of TNF-α, IL1ß, IL6, and IFN-γ compared to placebo. Similarly, it did not improve the disability in patients.

The survey of mindfulness in multiple sclerosis patients and its association with attachment style.

BACKGROUND: Mindfulness may be conceptualized as a dispositional trait which differs across individuals, so this study was, therefore, designed to determine the survey of mindfulness in multiple sclerosis (MS) patients and its association with attachment style. MATERIALS AND METHODS: This was a cross-sectional study which was conducted in Kashani Hospital affiliated to Isfahan University of Medical Sciences, Iran, in 2013. Samples were 210 adult patients who suffered from MS completed demographic and disease characteristics questionnaire, Five Factor Mindfulness Questionnaire and adult attachment style. The SPSS version 16 software was used to conduct statistical tests including t-test, NOVA, and Pearson correlation. RESULTS: The means of age and duration of illness were (33/96 ± 9/5) years and (24/3 ± 6/3) month, respectively. Most patients were married (66/1%), without university education (62/8%) and with incomes suffice (63%). The majority of the patients had received beta-interferon (55/4%) as their main treatment. The mean ± standard deviation attachment style and mindfulness were 25/6 ± 11/6 and 79/8 ± 25/6, respectively. Furthermore, there was a significant negative correlation between the attachment style score and mindfulness score (P = 0.001, r = -0.32). CONCLUSION: The result shows that stronger association between mindfulness and attachment can reflect the beneficial effects of mindfulness interventions on both mindfulness and attachment and it can provide some evidence that mindfulness interventions may enhance secure attachment.

A comparison the effects of reflexology and relaxation on the psychological symptoms in women with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) occurs with a variety of physical and psychological symptoms, yet there is not a conclusive cure for this disease. Complementary medicine is a current treatment which seems is effective in relieving symptoms of patients with MS. Therefore, this study is aimed to determine and compare the effects of reflexology and relaxation on anxiety, stress, and depression in women with MS. SUBJECTS AND METHODS: This study is a randomized clinical trial that is done on 75 women with MS referred to MS Clinic of Kashani Hospital. After simple non random sampling, participants were randomly assigned by minimization method to three groups: reflexology, relaxation and control (25 patients in each group). In the experimental groups were performed reflexology and relaxation interventions within 4 weeks, twice a week for 40 min and the control group were received only routine treatment as directed by a doctor. Data were collected through depression anxiety and stress scale questionnaire, before, immediately after and 2 months after interventions in all three groups. Chi-square, Kruskal-Wallis, repeated measures analysis of variance and one-way analysis of variance and least significant difference post hoc test via SPSS version 18 were used to analyze the data (P < 0.05) was considered as significant level. RESULTS: The results showed a significant reduction in the severity of anxiety, stress and depression during the different times in the reflexology and relaxation groups as compared with the control group (P < 0.05). CONCLUSION: The results showed that reflexology and relaxation in relieving anxiety, stress and depression are effective in women with MS. Hence, these two methods, as effective techniques, can be recommended.

A comparison of the effects of reflexology and relaxation on pain in women with multiple sclerosis.

BACKGROUND: Pain is a common and significant symptom in many individuals with multiple sclerosis (MS). The presence and severity of pain in individuals with MS has also been shown to be associated with higher levels of depression, functional impairment, and fatigue. It is common for MS patients and their caregivers to worry about narcotic addiction in the management of chronic pain. Therefore, this study aimed to determine and compare the effects of reflexology and relaxation on pain in women suffering from MS. METHODS: This study was a single-blind randomized clinical trial performed on 75 patients with MS referred to the MS Clinic of Ayatollah Kashani Hospital (Isfahan, Iran). After simple non-random sampling, using the minimization method, participants were randomly assigned to the three groups of reflexology, relaxation, and control. In the experimental groups, foot reflexology and relaxation interventions (Jacobson and Benson) were performed within 4 weeks, twice a week for 40 min. The control group received routine care and medical treatment as directed by a doctor. Data were collected using the Numerical Rating Scale before, immediately after, and 2 months after interventions in all three groups. Data analysis was performed using SPSS version 18 and descriptive and inferential statistical tests. RESULTS: Findings obtained from analysis of variance (ANOVA) showed no significant differences between mean pain intensity scores in the three groups preintervention and 2 months after interventions (p > 0.05). However, this difference was statistically significant immediately after the study (p < 0.05). Findings obtained from repeated measures ANOVA showed that the severity of pain significantly differed during different times in reflexology and relaxation (p < 0.05); however, this difference was not significant in the control group (p > 0.05). Furthermore, Fisher's least significant difference (LSD) revealed a significantly higher reduction in pain intensity scores in the reflexology group after the intervention, compared with the two other groups, but showed no significant differences between relaxation and control groups. There were no significant differences between the three groups 2 months after the interventions (p > 0.05). CONCLUSIONS: The results showed that both interventions are effective on relieving pain in women with MS; however, it appears that the effect of reflexology on pain reduction is greater than that of relaxation. Hence, these two methods can be recommended as effective techniques.

Comparing the effects of reflexology and relaxation on fatigue in women with multiple sclerosis.

BACKGROUND: Fatigue is the most common and highly disabling symptom of multiple sclerosis (MS) that has negative effects on employment, the process of socialization, compliance with the disease, and other factors effective on activities of daily living. The usage of complementary and alternative medicine methods in MS patients is higher than in the general population. However, there is no scientific evidence to support their effectiveness. Therefore, this study aimed to compare the effects of reflexology and relaxation on fatigue in women with MS. MATERIALS AND METHODS: This study is a single-blinded randomized clinical trial that was done on 75 patients with MS who referred to the MS Clinic of Ayatollah Kashani Hospital (Isfahan, Iran). After simple non-random sampling, participants were randomly assigned by minimization method to three groups: Reflexology, relaxation, and control groups (25 patients in each group). In the experimental groups, the interventions foot reflexology and relaxation (Jacobson and Benson) were performed for 4 weeks, twice a week for 40 min in each session, and the control group received care and routine medical treatment as directed by a physician. Data were collected through a questionnaire and the fatigue severity scale before, immediately after, and 2 months after interventions from all three groups. Data analysis was performed by SPSS version 18 using descriptive and inferential statistical methods. RESULTS: Findings obtained from analysis of variance (ANOVA) showed that there was no significant difference in the mean fatigue severity scores in the pre-interventions between the three groups (P > 0.05), but there was significant difference immediately after and 2 months after interventions between the three groups (P < 0.05). Findings obtained from repeated measures (ANOVA) showed that there was significant difference in the mean fatigue severity scores during different times between the three groups (P < 0.05), while this difference was not significant in the control group (P > 0.05). Furthermore, least significant difference post-hoc test revealed that the mean scores of fatigue severity immediately after intervention was lower in the reflexology group than in the other two groups and were lower in the relaxation group than in the control group; 2 months after interventions, the mean scores of fatigue severity were lower in the reflexology group than in the other two groups, but there was no significant difference between the two groups of relaxation and control (P > 0.05). CONCLUSIONS: It seems that both interventions were effective in reducing fatigue, but the effects of reflexology on reducing fatigue were more than those of relaxation. Hence, as these two methods are effective and affordable techniques, they can be recommended.

Preventive Effects of a Three-month Yoga Intervention on Endothelial Function in Patients with Migraine.

BACKGROUND: Migraine is a neurovascular disorder and any interventions improving endothelial function may contribute to its treatment and prevention of vascular complications like ischemic stroke. Yoga has been shown to have several beneficial effects on cardiovascular systems. However, no randomized controlled studies to date have investigated its effects on endothelial function of migraineurs. METHODS: A total of 42 women patients with migraine were enrolled and randomized into either a Yoga exercise group or a control group. The control group received only medication for 12 weeks and the Yoga group was placed in yoga training program in addition to the same medical treatment. Blood test was given from all patients in order to measure plasma levels intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) after yoga training program. RESULTS: Totally 32 patients were participated in the final analyses (yoga: n = 18, control: n = 14). By analyzing data between yoga and control groups after the treatment period, there was a significant decreased in plasma level of VCAM in yoga group compare with the control group (15.29 ± 2.1 ng/ml vs. 21.70 ± 3.0 ng/ml, P < 0.05), whereas there was no significant difference in ICAM level between groups (19.1 ± 1.8 ng/ml vs. 20.97 ± 1.9 ng/ml P > 0.05). CONCLUSIONS: It seems that yoga exercises, as a complementary treatment beside pharmacological treatments, can be potentially an effective way of improving vascular functions in migraineurs.

The relation between Vitamin D status with fatigue and depressive symptoms of multiple sclerosis.

BACKGROUND: The relation between Vitamin D deficiency with depressive and fatigue symptoms in both Multiple sclerosis (MS) patients and healthy population have been reported. To represent our regional achievement in this field we investigated the relation between Vitamin D status with fatigue and depressive symptoms in MS patients. MATERIALS AND METHODS: In two hundred MS patients, depressive symptoms and fatigue were measured using Beck PC (BDI-PC) and FFS scale, respectively. Venous blood sample was obtained from all participants and serum 25-hydroxy Vitamin D was measured by radioimmunoassay (RIA) method. Mean score of FSS, BDI-PC and EDSS were compared in patients with normal and low level of Vitamin D. The relation between FSS, BDI-PC score, EDSS and low Vitamin D status was determined. RESULTS: There was a moderate significant correlation between MS disability evaluated by EDSS and fatigue (r = 0.37, P < 0.001) and depression (r = 0.26, P < 0.001). The prevalence of low Vitamin D status was 48.5%. Low Vitamin D status was inversely associated with depressive symptoms of patients with MS (P = 0.02 rs = -0.16), but there was not significant correlation between Vitamin D and fatigue symptoms (P = 0.2). CONCLUSION: More interventional studies for determining the role of Vitamin D supplements in this regard is recommended.

Comparison of the effect of baclofen and transcutaneous electrical nerve stimulation for the treatment of spasticity in multiple sclerosis.

OBJECTIVE: The aim of this study was to compare the relative efficacy of baclofen and self-applied transcutaneous electrical nerve stimulation (TENS) for the treatment of spasticity in the lower extremities in multiple sclerosis (MS). METHODS: A randomized controlled clinical trial was conducted from September 2010 to June 2011. Fifty-two patients with MS presenting muscle spasm in the leg at 20-50 years of age were randomly allocated to receive a four-week treatment course of either baclofen (10 mg twice daily, increasing over three weeks to 25 mg) or self-applied TENS. Response to treatment was assessed at four weeks after commencement of the intervention by modified Ashworth scale (MAS). RESULTS: Spasticity decreased in both groups. Of the 26 people treated with TENS, the mean (standard deviation (SD)) MAS decreased from 1.77 (0.29) at baseline to 0.73 (0.70) at the four-week follow-up (P < 0.001). Correspondingly, in the 26 people treated with baclofen, the mean (SD) MAS decreased from 1.73 (0.38) to 1.15 (0.63) (P < 0.001). The mean difference in MAS score at the four-week follow-up was significantly lower in the TENS group than the baclofen group (mean difference -0.42; 95% CI, -0.79, -0.05; P < 0.05). DISCUSSION: This study demonstrates that both baclofen and TENS can be effective in reducing MS-related spasticity. The mean MAS score was significantly lower in the TENS group. However given the side-effect profile of baclofen, TENS may have some benefits over baclofen.

Effects of adjunct glucosamine sulfate on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized, placebo-controlled trial.

OBJECTIVES: Glucosamine has been safely used to relieve osteoarthritis. The aim of this preliminary study was to evaluate the effect of glucosamine sulfate in combination with current disease modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis (RRMS). METHODS: A phase II double-blind placebo-controlled randomized clinical trial conducted between February and October 2007 included 97 patients with confirmed RRMS aged 17-55 years. They were randomly allocated to receive 6 months of treatment with either oral glucosamine sulfate (1000 mg/day) or placebo combined with disease-modifying therapy. Response to treatment was assessed at 6 months. Primary and secondary outcome measures were number of relapse and changes in mean Expanded Disability Status Scale (EDSS). RESULTS: In 46 patients treated with glucosamine sulfate, mean (SD) relapse rate decreased from 1.1 (0.7) at baseline to 0.4 (0.5) at the end of study period (P<0.05). In the 51 patients treated with placebo, the mean (SD) relapse rate did not change. After 6 months, 63.0% of patients receiving glucosamine sulfate remained relapse-free compared to 54.9% of those given placebo (P>0.05). Average EDSS at the end of trial did not differ between groups (mean difference: -0.1; 95% CI: -0.5-0.2). DISCUSSION: Adding glucosamine sulfate to routine disease modifying-therapy had no significant effect on relapse rate or disease progression during the treatment period. A larger phase-III multicenter study of glucosamine sulfate in RRMS is warranted to more assess the efficacy of this intervention.

Sensory complaints of the upper extremities in multiple sclerosis: relative efficacy of nortriptyline and transcutaneous electrical nerve stimulation.

OBJECTIVE: The aim of this study was to evaluate the relative efficacy of nortriptyline and self-applied transcutaneous electrical nerve stimulation (TENS) in the treatment of pain and/or sensory complaints of the upper extremities in people with multiple sclerosis (MS). METHODS: A randomized clinical trial conducted from September 2005 to September 2006. Fifty-nine people with clinically definite MS aged 15 to 50 years were randomly allocated to receive an 8-week treatment course of either nortriptyline (10 mg daily increment over 1 week to 50 mg) or self-applied TENS. Response to treatment was assessed at 2, 4, and 8 weeks after commencement of the intervention. RESULTS: TENS seemed to be equivalent in efficacy to nortriptyline. A significant decrease in visual analog scale scores of pain and/or sensory complaints of the upper extremities occurred in both groups. Of the 29 people treated with TENS, the mean (SD) intensity of pain and/or sensory complaints decreased from 5.3 (1.6) at baseline to 2.8 (1.5) at 8 weeks follow-up (P < 0.001). Correspondingly in the 30 people treated with nortriptyline, the mean (SD) intensity of pain and/or sensory complaints decreased from 4.9 (1.9) to 3.3 (2.1) (P < 0.001). The mean difference in visual analog scale score at 8 weeks follow-up was not significant between the 2 groups (mean difference -0.5; 95% confidence interval, -1.5-0.5). DISCUSSION: This study demonstrates that both nortriptyline and TENS can be effective in reducing the intensity of pain and/or sensory complaints in the upper extremities of people with MS. However given the side-effect profile of nortriptyline, TENS may have some benefits over nortriptyline. This modest reduction in the intensity of pain and/or sensory complaints suggests that physicians should carefully weigh the risk and benefits of nortriptyline and TENS in people with MS with pain and/or sensory complaints.