Multiple sclerosis (MS) is described as a chronic inflammatory, demyelinating disease of the central nervous system on an autoimmune basis, which is the most frequent reason for nontraumatic ...disability in youth. The efficacy and safety of β‐D‐nannuronic acid (M2000) as a novel immunosuppressive drug (patented PCT/EP2017/067920) has been shown in an experimental model of MS and also in a phase 2 clinical trial. The effects of M2000 on SOCS1, SOCS3, TRAF6, and SHIP1 gene expression and also serum levels of IL‐6 and TNF‐α in secondary progressive multiple sclerosis patients have been assessed in this study. In this study, 14 secondary progressive multiple sclerosis patients and 14 healthy subjects (as the control group) were recruited from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). Gene expression of SOCS1, SOCS3, TRAF6, and SHIP1 was measured at baseline and after 6 months of therapy with M2000 using a quantitative real‐time polymerase chain reaction method. Furthermore, the serum levels of IL‐6 and TNF‐α were assessed by the enzyme‐linked immunosorbent assay method. Our results showed that the gene expression of SOCS1, SOCS3, and SHIP1 was increased after 6 months of therapy with M2000 in MS patients. Moreover, the serum levels of IL‐6 and TNF‐α of patients declined compared with baseline, but this was not statistically significant. The results of this study demonstrated that M2000, with immunosuppressive properties, could upregulate SOCS1, SOCS3, and SHIP1 genes in patients with secondary progressive multiple sclerosis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Multiple sclerosis (MS) is a chronic neurologic disease defined by inflammation and demyelination of the central nervous system that comes with variable degrees of axonal and neuronal damage. The ...efficacy of β‐D‐mannuronic acid (M2000) as a novel drug with immunosuppressive properties (patented: PCT/EP2017/067920), has been shown in an experimental model of MS. In this study, the effects of M2000 on interleukin (IL)‐1β, IL‐17A, signal transducer and activator of transcription (STAT) 1, and STAT3 gene expressions and Toll‐like receptor 2 (TLR2) and toll‐like receptor 4 (TLR4) molecules in patients with secondary progressive MS were evaluated. In this study, 14 patients with secondary progressive MS and 14 healthy subjects (as control group) were entered from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). The gene expressions of IL‐1β, IL‐17A, STAT1, and STAT3 were assessed at the baseline and then measured after 6 months of therapy with M2000 by using the quantitative real‐time polymerase chain reaction method. Moreover, the expressions of TLR2 and TLR4 molecules on peripheral blood mononuclear cells were evaluated by the flow cytometry method. The gene expressions of IL‐17A, STAT1, and STAT3 in patients with MS decreased after 6 months of therapy with M2000 comparing before treatment. Also, the gene expression of IL‐1β decreased numerically after 6 months. Furthermore, the expressions of TLR2 and TLR4 on PBMCs of the patients declined when compared to baseline. The results of this investigation revealed that M2000 could downregulate IL‐17, STAT1, and STAT3 genes in patients with secondary progressive MS and also reduce the expressions of TLR2 and TLR4 on PBMCs. Moreover, M2000 declined numerically IL‐β gene expression.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•MMP-9 levels increasing was significantly lower in patients who received Memantine.•The non-significant effect of Memantine on lowering the increase in MMP-2 levels.•Memantine significantly improved ...neurologic function evaluated by NIHSS.•Memantine significantly improved neurologic function based on the increase in BI.•No serious adverse events were recorded for high dose Memantine.
Memantine was suggested as a promising treatment for stroke due to its neuroprotective property and efficacy in reducing ischemic brain injury and improving post-ischemic neurological recovery. This pilot, open-label, randomized clinical trial was conducted to investigate the impact of memantine on serum concentrations of matrix metalloproteinases (MMP)-2 and MMP-9, as neuronal damage biomarkers, and neurologic function evaluated by the National Institute of Health Stroke Scale(NIHSS) and Barthelindex(BI) in patients with ischemic stroke. Admitted patients with mild to moderate ischemic stroke were assessed for eligibility, and eligible patients were randomized to the intervention or control group. Enrolled patients in the intervention group received 20 mg memantine every 8 h for five days and then 20 mg daily for three months. Both groups managed with the standard treatments. From 77 randomized patients, 29 participants in the control group and 24 patients in the intervention group completed the study. Data showed that the increase in the serum concentrations of MMP-9 within the first 5 days of the study was significantly lower in the intervention group (P = 0.005). This effect of memantine on the MMP-2 was not significant (P = 0.448). memantine also could significantly improve the neurologic function of the patients according to NIHSS (P < 0.0001) and BI (P = 0.002) during hospitalization and after that. In conclusion, memantine could be considered as a neuroprotective agent in patients with mild to moderate ischemic stroke, based on its significant effects on reducing brain damage and improving neurologic function of the patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
Huntington's disease is a progressive neurodegenerative disease that typically manifests with Choreic movements, psychological disorders, and cognitive decline. Some patients can initially present ...atypical movements other than the usual symptoms, such as parkinsonism, ataxia, and dystonia. In this report, we present an HD patient who presented with atypical parkinsonism.
Huntington's disease should be considered in the differential diagnosis of late‐onset parkinsonism, especially if family history is positive and patients have atypical manifestations of atypical parkinsonism.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare disease with unknown risk factors. The role of oxidative stress and nutritional factors is imprecise in NMOSD development. Therefore, ...this paper aims to evaluate the effects of dietary total antioxidant capacity (TAC) on the odds of NMOSD.
Design/methodology/approach
Dietary TAC was determined in 70 definite NMOSD cases and 164 healthy controls in term of Ferric Reducing Antioxidant Power (FRAP) method. A validated 168-item semi-quantitative food frequency questionnaire (FFQ) was used for dietary assessment. Three multivariate regression models were applied to analyze the odds of NMOSD across the TAC quartiles.
Findings
A significant inverse association was found between dietary TAC and odds of being assigned to the NMOSD group in all three regression models. In the fully adjusted model ORs (95% CI) in the second, third and fourth quartiles of TAC vs the first quartile were as follows: 0.11 (0.04-0.29), 0.05 (0.01-0.16) and 0.01 (0.00-0.05), respectively. Odds of NMOSD also indicated a significant decreasing trend across the quartiles of dietary TAC (p-trend: <0.01). Total energy (p < 0.01) as well as consumption of vegetables (p < 0.01), whole grains (p < 0.01), tea and coffee (p < 0.01), legumes (p < 0.01) and poultry (p < 0.01) significantly increased through the TAC quartiles.
Originality/value
In the present study, a new hypothesis was proposed concerning the influence of dietary TAC on the odds of NMOSD. A diet rich in foods with high TAC can be effective in the modification of the NMOSD odds.
Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study ...determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Every patient diagnosed with definite multiple sclerosis (MS) should begin disease modifying therapies. Cinnomer
contains 40 mg glatiramer acetate (GA) and is available in prefilled syringes and ...autoinjector devices.
A phase IV multicenter study was conducted to explore the safety and effectiveness of Cinnomer
in the treatment of MS. Study-related data were collected for 14 months.
Totally, 368 Iranian relapsing-remitting MS patients in nine cities were enrolled. The patients were either treatment naïve (n=191) or switchers (n=177). Cinnomer
treatment was associated with a significant reduction in annual relapse rate (ARR) (RR: 0.65, 95% CI: 0.43, 0.98). Final mean Expanded Disability Status Scale (EDSS) scores showed improvement from baseline (difference: -0.21, 95% confidence interval (CI): -0.34, -0.08). There was a significant decrease in gad-enhancing lesions during treatment (difference: -0.38, 95% CI: -0.64, -0.12). The mean score for the depression measure (21-item BDI-II questionnaire) significantly improved (difference: -2.39, 95% CI: -3.74, -1.03). There was a significant change in the "psychological well-being" dimension (
=0.02) (in line with BDI-II scores) and "rejection" MusiQoL dimensions (
=0.04). The adverse events documented throughout the study were not unexpected for GA and were principally not serious.
Safety measures were in line with the known profiles of GA. The results suggest that Cinnomer
is effective with respect to clinical outcomes and from the patient's perspective and in reducing MRI-measured MS activity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory disorder with a tendency to affect the spinal cord and optic nerves. As NMOSDs have a predilection for women of reproductive age ...and adopt an aggressive course during pregnancy, appropriate treatment strategies before conception and during pregnancy should be well-considered.
In this report, the pregnancy outcome of eight pregnancies following rituximab treatment was assessed, which led to 50% live births with mean birth weight of 2777.50 (SD: 545.92) grams. Two patients had abortions due to doctor's recommendation. One pregnancy led to intrauterine fetal death (IUFD) due to nuchal cord. No spontaneous abortions were encountered. Two patients received rituximab during pregnancy. No major malformations or serious neonatal infections were encountered.
Rituximab should be administered by caution in NMOSD patients who want to be pregnant and the probable adverse effects of the drug should be discussed by patients.
The time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the ...time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients.
The present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI).
Overall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS.
The findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients’ access to medical facilities and MS specialists.
•The mean time from clinical symptoms onset to diagnosis of MS was 13.42 months.•in cases registered in the National MS Registry of Iran.•More than half of the MS cases were diagnosed within one-month interval.•Age at symptoms onset, age at the time of diagnosis, male sex and type of MS.•were associated factors to a late diagnosis in Iranian MS subjects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
