Safety and efficacy of fingolimod in Iranian patients with relapsing-remitting multiple sclerosis: An open-label study.

BACKGROUND: Fingolimod was the first oral therapy approved for treating relapsing-remitting multiple sclerosis (RRMS) in 2010. This open-label study evaluated the safety and efficacy of fingolideR, 0.5 mg in Iranian MS patients during one-year follow-up. METHODS: A multicenter, open-label, longitudinal was designed to evaluate the safety and efficacy of fingolideR, 0.5 mg over a one-year follow-up period across 11 centers. The patients were visited by their neurologists every two months to evaluate possible adverse events and clinical disease activity considered by recording Kurtzke's Expanded Disability Status Scale (EDSS). RESULTS: A total of 252 patients with the mean treatment duration of 343±45.70 days were. 20 patients experienced adverse events (AEs) and serious adverse events (SAEs) such as resistant urinary tract infection (UTI), premature atrial contraction (PAC), skin allergic reaction, macular edema, chicken pox, zona, panic attacks, and exacerbations associated with steroids treatment, all of which led to FingolideR discontinuation. The mean EDSS decreased from (2.15±1.29, 95%CI: 1.99to2.32) at baseline to (1.85±1.22, 95%CI: 1.68to2.02) at 12th month (final visit) while a p-value revealed significant differences comparing baseline and final EDSS (p<0.001). Mean annualized relapse rate (ARR) of the patients in one year prior to the study was (0.006±0.016, 95%CI: 0.004to0.008) which changed to (0.005±0.016, 95%CI: 0.003to0.007) at the end of the study period. Patients with a 12-month period of fingolideR treatment experienced sustained ARR and disease progression (p<0.001). CONCLUSION: The obtained findings suggest that the administration of FingolideR, 0.5 mg (Fingolimod, Osvahpharma, Tehran, Iran) is safe and efficient for Iranian MS patients.

Evaluation of Neuroprtective Effects of L-Carnitine and Fat Emulsion in the CVA Patients: A Prospective, Randomized, Double Blind, Clinical Trial.

Cerebral infarction presents with neurological deficits caused by the death of neurons in a focal area of the brain. S100B is a biomarker that increases in brain damage. Neuroprotectives can reduce the brain sequels after neurological insult. The purpose of this study was to evaluate the neuroprotective effects of L-carnitine and Fat emulsion (Lipofundin®) alone and in combination in patients with ischemic stroke. In a prospective, RCT, and double-blind study 100 patients with MCA ischemic cerebrovascular accident who were admitted in the first 24 h of injury entered the study. The patients were randomly assigned into four groups of L-carnitine, fat emulsion, L-carnitine plus fat emulsion and control. Fat emulsion 10%, 500 mL, was infused over 6 to 12 h and 1 gr of L-carnitine (10 mL of solution) was administered orally to patients in addition to common therapies, according to the American Heart Association and American Stroke Association (AHA/ASA) guidelines. The patients in the control group received only the usual treatment according to stroke guidelines. Blood samples before the intervention, then after 24 h, 48 h, and 7 days later were taken and immunoenzymatic colorimetric method was used for quantitative determination of S100B concentration in the patients' serum. In the within group analysis, all of our treatment interventions (except control group) have decreased S100B levels statistically significant (P < 0.05). Moreover, changes in observed levels of S100B before and after intervention were different between the groups and the observed differences were statistically significant (P = 0.01). In the GEE model, it was found that S100B levels in the L-carnitine plus fat emulsion group decreased more than the control group and this decline has been statistically significant [P = 0.02, 20.47 (CI 95%: 6.25-34.41)], but in comparison of L-carnitine and fat emulsion group with control group, did not reached statistical significance (P > 0.05). Based on the results obtained from this study, it seems that L-carnitine with fat emulsion could lead to neuroprotective effects with a significant reduction in the S100B biomarker.

Multiple sclerosis and environmental risk factors: a case-control study in Iran.

Studies have shown an increase in the incidence of MS in Iran. The aim of our study was to evaluate the relationship between environmental exposure and MS in Iran. This case-control study was conducted on 660 MS patients and 421 controls. Many environmental factors are compared between the two groups. Our findings demonstrated that prematurity ([OR = 4.99 (95% CI 1.34-18.68), P = 0.017]), history of measles and mumps ([OR = 1.60 (95% CI 1.05-2.45), P = 0.029; OR = 1.85 (95% CI 1.22-2.78), P = 0.003, respectively]), breast feeding [OR = 2.90 (95% CI 1.49-5.65), P = 0.002], head trauma in childhood ([OR = 8.21 (95% CI 1.56-43.06), P = 0.013]), vaccination in adulthood ([OR = 4.57 (95% CI 1.14-18.41), P = 0.032, respectively]), migraine ([OR = 3.50 (95% CI 1.61-7.59), P = 0.002]), family history of MS, IBD, migraine, and collagen vascular diseases ([OR = 2.73 (95% CI 1.56-4.78), P < 0.001], [OR = 3.14 (95% CI 1.460-6.78), P = 0.004; OR = 3.18 (95% CI 1.83-5.53), P < 0.001; OR = 1.81 (95% CI 1.03-3.20), P = 0.040, respectively]), stressful events ([OR = 32.57 (95% CI 17.21-61.64), P < 0.001]), and microwave exposure ([OR = 3.55 (95% CI 2.24-5.63), P ≤0.001]) were more in the MS group. Sun exposure ([OR = 0.09 (95% CI 0.02-0.38), P = 0.001]), dairy and calcium consumption ([OR = 0.44 (95% CI 0.27-0.71), P = 0.001]), diabetes mellitus ([OR = 0.11 (95% CI 0.01-00.99), P = 0.049], and complete vaccination during childhood appeared to decreased MS risk. Our results investigated many risk factors and protective factors in Iran.

Association between interleukin-32 polymorphism and multiple sclerosis.

BACKGROUND AND AIM: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Environmental and genetic factors play a key role in the development of the disease. Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as TNF-α, IL-6, IL-1ß, and MIP-2. The present study was an attempt to reveal any association between IL-32 levels and C/T promoter SNP with susceptibility to MS. METHODS: This case control study recruited a total of 304 subjects including 132 MS patients and 172 sex- and age-matched healthy controls. Clinical and epidemiological characteristics of the RRMS, PPMS, and PPMS populations were assessed. Serum levels and C/T polymorphism of IL-32 were determined by ELISA and RFLP-PCR methods, respectively. RESULTS: Serum levels of IL-32 were significantly different between MS patients and controls. IL-32 was dramatically higher in the patients than that healthy controls (2297.4±280.2 ver. 712.9±90.2, p=0.001). C allele was prominent in MS patients than the controls and might increase the risk of MS up to 1.6 fold (95% CI; 1.02-2.4, p=0.038). In addition, the presence of C allele enhanced IL-32 production drastically. CONCLUSION: This is the first study in which IL-32 gene promoter C/T polymorphism and its serum levels were investigated. The increase in serum levels of IL-32 in accordance with additive effect of the presence of C allele in MS patients might introduce IL-32 as a key player in MS pathogenesis or immunedysregulation.

Risk factors of Multiple sclerosis and their Relation with Disease Severity: A Cross-sectional Study from Iran.

BACKGROUND: Many risk factors have been investigated in multiple sclerosis (MS); however, few studies have focused on the association between risk factors and the disease severity. The aim of our study was to evaluate the association between some of these risk factors and MS severity in a population sample of Iranian patients. METHODS: This cross-sectional study was conducted on 660 patients with MS. In addition to demographic variables, many potential risk factors were recorded. To compare the severity, progression index (PI) was calculated. This index is created by current Expanded Disability Status Scale (EDSS) /disease duration. RESULTS: Univariate analysis revealed that active smoking status is related with MS severity. (P-value = 0.012). Furthermore, our findings demonstrated that age at the disease onset [P < 0.001; OR = 1.05 (95% CI: 1.03-1.07)], female gender [P = 0.002; OR = 1.86 (95% CI: 1.24-2.77)] and marital status [P = 0.002; OR = 1.71 (95% CI: 1.21-2.41)] correlated with the severity of MS in the adjusted model. MS severity was observed to be related with high school and academic studies ([P = 0.004; OR = 0.56 (95% CI: 0.38-0.83)], [P = 0.001; OR = 0.52 (95% CI: 0.35-0.78)]) (Primary/secondary school studies are used as reference). Moreover, there was an association between MS severity and occupation (white collar, pink collar) ([P = 0.006; OR = 0.32 (95% CI: 0.14-0.73)], [P = 0.007; OR = 0.47 (95% CI: 0.27-0.81)]) (Student is used as reference). Furthermore, the results showed a significant correlation between vision and motor symptoms as an initial symptom and PI (P = 0.001, P = 0.025). CONCLUSION: Due to high cost of MS care and its moderate to severe disability, identification of factors influencing the MS severity is important. Our results demonstrated that the major modifiable factors related with MS severity in Iranian population, some protective and some promotive, were smoking, education, marital status and occupation. Prospective studies on larger scale are needed for further proof of these results.

A Survey of Severity and Distribution of Musculoskeletal Pain in Multiple Sclerosis Patients; a Cross-Sectional Study.

BACKGROUND: Pain, a common phenomenon in multiple sclerosis (MS) patients, is associated with many symptoms and problems. AIM: To investigation severity and distribution of musculoskeletal pain in MS patients. METHODS: In this cross-sectional study, 115 members of the Mazandaran MS Association with confirmed MS were randomly selected to participate in the study. The patients were asked to fill out Numerical Rating Score and Nodric questionnaires, respectively. The data was analyzed by SPSS ver. 16 software. RESULTS: The mean age of the participants was 30.43±5.86 years and 88 cases (76.5%) were female. The mean disease duration was 26.34±24.32 months and 87.8% of the cases were experiencing pain at the time of study. The mean pain severity was 3.75±2.25 and worst pain experienced was 5.73±2.12. The most common pain sites were: the knees (55.7%), wrist (43.5%), and neck (41.7%). Women experience higher prevalence of shoulder, upper back, and ankle pain (P<0.05). In 62 cases (53.91%) MS interfered with daily functioning at least for a time. The prevalence of upper back and neck pain was higher in cases with a shorter disease duration (P<0.05). CONCLUSIONS: Pain was very common in patients with MS and not relevant to sex or age. In the majority of the cases more than 1 limb was involved and the prevalence of pain in the lower limbs was higher, especially in the knees. In females, the prevalence of pain in the shoulders, upper back, and ankle was higher compared to males. Also, neck and upper-back pain were found in the early stages of the disease.

Ischemic stroke as a rare manifestation of aluminum phosphide poisoning: a case report.

Aluminum phosphide (AlP) is a solid fumigant which is widely used for a suicide attempt in Iran. Although neurologic symptoms are commonly reported, cerebrovascular stenosis is rare in AlP poisoning. We described ischemic stroke as a delayed complication of AlP intoxication. A 30-year-old man was admitted because of sudden onset left side hemiplegia, 11 days after intentional ingestion of three rice tablets. Investigations revealed in situ thrombosis in right middle cerebral artery (MCA) while other causes of stroke in young adults were excluded. Ischemic stroke should be considered as a delayed complication of AlP intoxication even after the acute phase of intoxication.

Toll like receptor-4 896A/G gene variation, a risk factor for migraine headaches.

BACKGROUND: The pathogenesis of migraine involves immune-mediated mechanisms in the vascular endothelium. Toll like receptor 4 (TLR-4) is a signaling receptor of innate immunity which plays a role in various neuropathologies related to neuron inflammation. OBJECTIVE: This case/control study is aimed to investigate whether TLR-4 896A/G variation is related to migraine headaches in an Iranian population. METHODS: A total of 170 migraine patients (130 females, mean age 33.24 ± 11 years) and 170 age, sex, and ethnicity matched healthy controls (118 females, mean age of 31 ± 10 years) were recruited. Genotyping was carried out using the tetra primer amplification refractory mutation system (ARMS)-PCR. RESULTS: The frequency of G allele was higher in migraine patients than the controls (15% vs. 4.7%; p<0.0001). Interestingly, the distribution of heterozygous 896A/G genotype statistically differed between migraineurs and controls (25.3% vs. 8.2%, p=0.00002, OR 3.87, 95% CI; 2.02-7.4). Multivariate logistic regression analysis indicated that G allele in affected female migraineurs is an independent factor associated with increased risk of migraine (OR 3.2, 95% CI 1.23-8.24, p=0.01). CONCLUSION: Our results showed TLR-4 polymorphism as a genetic risk factor for migraine. However, further studies in different populations are required to elucidate the precise role of TLR-4 896A/G mutation in susceptibility to migraine.

R-carrying genotypes of serum paraoxonase (PON1) 192 polymorphism and higher activity ratio are related to susceptibility against ischemic stroke.

The polymorphic gene of serum paraoxonase (PON1) and its activity involved in atherosclerosis. The purpose of the study was to analyze PON1 192 Q/R polymorphism and the enzyme activities in ischemic stroke. The polymorphism as the most common polymorphism in PON1 gene coding sequence is associated with variation in the enzyme activity and vascular disease. The study included 85 stroke patients and 71 control subjects. PON1 192 polymorphism was genotyped using PCR protocol. Paraoxonase activity (Para) and arylesterase activity (Aryl) were determined spectrophotometrically using paraoxon and phenylacetate as the substrates. The QR and RR genotypes were more frequent in stroke population compared to controls, resulting in a higher frequency of the R allele in patients (0.24 vs 0.18, OR = 1.41). Patients had significantly higher Para/Aryl ratio than that of controls (P = 0.016). In stroke patients, Para/Aryl and Para/HDL ratios increased with this order: QQ < QR < RR. Hypertension significantly increased the risk of ischemic stroke by 15-fold among R-containing people, while this was significantly increased 4-fold for QQ homozygotes. Smoking increased the risk of having ischemic stroke in both QQ homozygote and QR + RR group (OR = 2.84 and OR = 2.33, respectively). In conclusion, these data highlight the importance of PON1 192 R allele and high Para/Aryl ratio in susceptibility to ischemic stroke in the population. The presence of the 192 R allele potentiates the risk of stroke especially in hypertensive people. Decreased Aryl and increased Para/Aryl, Para/HDL and Aryl/HDL ratios may be markers indicated the increased susceptibility to ischemic stroke in the population.

MICB gene expression on peripheral blood mononuclear cells and susceptibility to multiple sclerosis in north of Iran.

Multiple sclerosis (MS) is an autoimmune multifactorial degenerative disease with detrimental affliction on central nervous system. MHC class I chain- related geneA,B(MICA and MICB) are nonclassical human leukocyte antigens that can affect on some diseases and also on transplantation. The purpose of this study was to evaluate the MICA and MICB MRNA expression in multiple sclerosis patients. In this study, we evaluated MICA and MICB MRNA expression in the peripheral blood mononuclear cells by reverse transcryptase-polymerase chain reaction(RT-PCR) in MS patients and normal controls. The results of this study showed that 32.6% of patients with progressive clinical outcome over expressed MICB genes in comparison with controls ( p=0.002). It is concluded that the high expression of MICB gene in MS patients is an important criterion of MS disease that it may be due to the interaction between MICB and its receptor on CD8+T or NK cells.