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Background: MLC601 and MLC901 showed neuroprotective and neuroregenerative properties and positive results in the treatment of dementia and cognitive impairment. This study aimed to investigate the long-term benefits of monotherapy with MLC601 and MLC901 in patients with Alzheimer's disease (AD). Methods: In this study, patients with AD, diagnosed by DSM-IV criteria, were enrolled. Patients have received MLC601 for four years, and their regimen has changed to MLC901 for another four years. Recruited patients were followed to assess the efficacy and safety first of MLC601 and MLC901. Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) were used to assess cognitive function. Safety was evaluated by monitoring adverse events (AEs) and abnormal findings in physical examinations or lab tests. Results: At the end of the trial, the changes in the mean (±SD) MMSE and ADAS-cog scores were 5.1 (3.09) and 12.5 (10.89), respectively. Both scores showed a significant change in repeated measure analysis, with the ADAS-cog score indicating a higher change than the MMSE score (P Conclusion: For more than eight years, we studied monotherapy with NeuroAid (MLC601, MLC901) in patients with AD. The study contributes further to the long-term safety and efficacy data of MLC in patients with AD. Trial Registration

ImportanceEpilepsy is one of the most common neurologic disorders globally. Cannabidiol (CBD) has been approved for the treatment of epilepsy, but its use has been associated with several different adverse events (AEs).ObjectiveTo investigate the frequency and risk of AEs developing in patients with epilepsy who are using CBD.Data SourcesPubMed, Scopus, Web of Science, and Google Scholar were searched for relevant studies published from database inception up to August 4, 2022. The search strategy included a combination of the following keywords: (cannabidiol OR epidiolex) AND (epilepsy OR seizures).Study SelectionThe review included all randomized clinical trials that investigated at least 1 AE from the use of CBD in patients with epilepsy.Data Extraction and SynthesisBasic information about each study was extracted. I2 statistics were calculated using Q statistics to assess the statistical heterogeneity among the included studies. A random-effects model was used in cases of substantial heterogeneity, and a fixed-effects model was used if the I2 statistic for the AEs was lower than 40%. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.Main Outcomes and MeasuresFrequency of each AE and risk of developing each AE in patients with epilepsy using CBD.ResultsNine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs. The overall risk ratios (RRs) for any grade and severe grade AEs were 1.12 (95% CI, 1.02-1.23) and 3.39 (95% CI, 1.42-8.09), respectively, for the CBD group compared with the control group. Compared with the control group, the CBD group had a greater risk for incidence of serious AEs (RR, 2.67; 95% CI, 1.83-3.88), AEs resulting in discontinuation (RR, 3.95; 95% CI, 1.86-8.37), and AEs resulting in dose reduction (RR, 9.87; 95% CI, 5.34-14.40). Because most of the included studies had some risk of bias (3 raised some concerns and 3 were at high risk of bias), these findings should be interpreted with some caution.Conclusions and RelevanceIn this systematic review and meta-analysis of clinical trials, the use of CBD to treat patients with epilepsy was associated with an increased risk of several AEs. Additional studies are needed to determine the safe and effective CBD dosage for treating epilepsy.

Background As a natural antioxidant, uric acid plays a protective role against neurodegenerative disorders, including Parkinson’s disease (PD). Therefore, the risk of PD has been found to be lower in people with hyperuricemia. In this article, we conducted a systematic review and meta-analysis to investigate whether gout affects the future risk of developing PD. Methods We searched PubMed, Scopus, the Web of Science, and Google Scholar to find relevant studies, up to March 16, 2022. Studies investigating the risk of PD, following a gout diagnosis, were included if they were cross-sectional, case–control or cohort studies. The Newcastle Ottawa Scale (NOS) checklist was used to assess the quality of all included studies. The meta-analysis was performed using STATA 17.0. Results Ten studies were included, which were comprised of three case-controls, six cohort studies and one nested case–control study. We found no significant association between gout and the risk of PD among both sexes (RR = 0.94, 95% CI: 0.86–1.04), although the association was significant for females (RR = 1.09; 95% CI: 1.02–1.17). Subgroup analysis also showed no significant findings by age group, whether they were receiving treatment for gout, study design, quality assessment score, and method of gout ascertainment. In contrast, the studies that defined PD according to the use of drugs showed significant results (RR = 0.82; 95% CI: 0.76–0.89). There was a significant publication bias on the association between gout and PD. Conclusions The presence of gout had no significant effect on the risk of subsequently developing PD. Further analyses are recommended to investigate the effects of demographic and behavioral risk factors.

Epilepsy has garnered increased public health focus because patients who suffer from epilepsy experience pronounced and persistent health and socioeconomic disparities despite treatment and care advances. The epidemiology of epilepsy is diverse in different countries and regions. This nationwide population-based cross-sectional study was conducted to determine the life time prevalence and health related factors of epilepsy for the first time in Iran through a two-phase door-to-door survey method. In phase I, a screening for epilepsy was performed on 68,035 people. Then in phase II, after the neurological evaluation of participants and reviewing medical records, 1130 subjects with epilepsy was confirmed. The life time prevalence of epilepsy was achieved to be 16.6 per 1000 people (95% CI 15.4–17.8) with the average age onset 19.1 ± 21.1 (active prevalence 9.5 per 1000 people). Focal seizure (59.3%), generalized epilepsy (38%) and unknown types of epilepsy (2.7%) were detected among participants. The overall life time prevalence of febrile convulsion was 4.1 per 1000 people. The frequency of attacks per year and per month were 3.0 ± 1.6 and 0.5 ± 0.1, respectively. Age-specific life time prevalence was highest among the age group of 15–19 years old [32.7 per 1000 persons (95% CI 29.1–36.8)] and it was higher in male (53.8%) than female (46.2%) participants. Our results showed that the life time prevalence of epilepsy in Iran is higher than worldwide average.

Interferon beta is currently the first line treatment of relapsing-remitting multiple sclerosis (RRMS). Different formulations of interferon beta are available. Avonex and CinnoVex are two interferon beta-1a being prescribed by neurologists in Iran. The aim of this study was to compare the four and half year outcome of Avonex and CinnoVex in patients with RRMS. A total 186 of patients with definite RRMS diagnosis were followed for four and half years. Patients were randomly assigned to receive either Avonex or CinnoVex. Patients were subsequently visited every 6 months, and MRI was also undertaken prior each visit. The efficacy end points were to compare mean scores of expanded disability status scale (EDSS) and the proportion of patients with MRI and clinical activity in follow-up visits between Avonex and CinnoVex. Safety end point was to compare the percentage of adverse events between two groups. One hundred and eighty-two patients completed the study. The population of study experienced a steady increase in EDSS during follow-up with a mean increase of 1.03. Repeated measures ANOVA revealed no statistically significant difference between Avonex and CinnoVex (p = 0.78). The most common adverse events were headache, myalgia, fatigue, fever, flu symptoms, injection site pain, and depression. Direct comparison of each adverse events revealed no meaningful difference between two groups except for only a few adverse events. There was no statistically significant difference in MRI activity and clinical activity between two groups. Avonex and CinnoVex showed similar efficacy and safety outcome in patients with RRMS.

Background and Aim: Mild cognitive impairment (MCI) is characterized by declined cognitive function greater than that expected for a person’s age. The clinical significance of this condition is its possible progression to dementia. MLC601 is a natural neuroprotective medication that has shown promising effects in Alzheimer disease. Accordingly, we conducted this randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of MLC601 in MCI patients. Methods: Seventy-two patients with a diagnosis of MCI were recruited. The included participants were randomly assigned to groups to receive either MLC601 or placebo. An evaluation of global cognitive function was performed at baseline as well as at 3-month and 6-month follow-up visits. Global cognitive function was assessed by Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) scores. Efficacy was evaluated by comparing global function scores between the 2 groups during the study period. Safety assessment included adverse events (AEs) and abnormal laboratory results. Results: Seventy patients completed the study, 34 in the MLC601 group and 36 in the placebo group. The mean changes (±SD) in cognition scores over 6 months in the MLC601 group were –2.26 (±3.42) for the MMSE and 3.82 (±6.16) for the ADAS-cog; in the placebo group, they were –2.66 (±3.43) for the MMSE and 4.41 (±6.66) for the ADAS-cog. The cognition changes based on both MMSE and ADAS-cog scores were statistically significant between the placebo and the MLC601 group (p < 0.001). Only 5 patients (14.7%) reported minor AEs in the MLC601 group, the most commonly reported of which were gastrointestinal, none of them leading to patient withdrawal. Conclusion: MLC601 has shown promising efficacy and acceptable AEs in MCI patients.

This study was designed to evaluate ALS progression among different subgroups of Iranian patients. Three hundred and fifty-eight patients from centres around the country were registered and their progression rate was evaluated using several scores including Manual Muscle Test scoring (MMT) and the revised ALS Functional Rating Scale (ALSFRS-R). Progression rate was analysed separately in subgroups regarding gender, onset site, stage of disease and riluzole consumption. A significant difference in MMT deterioration rate (p = 0.01) was noted between those who used riluzole and those who did not. No significant difference was observed in progression rates between male/female and bulbar-onset/limb-onset groups using riluzole. In conclusion, riluzole has a significant effect on muscle force deterioration rate but not functional scale. Progression rate was not influenced by site of onset or gender.

Aim: To evaluate the efficacy and tolerability of MLC601 in patients with mild to moderate Alzheimer disease (AD). Study Design: This is an open-label pilot study. Place and Duration of Study: It was conducted at three university referral centres in Iran from September 2009 until November 2011. Methodology: One-hundred and twenty four outpatients with mild to moderate AD who had previously failed to tolerate or benefit from treatment with Rivastigmine for 6 months at a dose of 2 to 12 mg per day were switched to a MLC601 regimen of one capsule three times per day for up to 18 months. Outcome measures included adverse events (AEs), withdrawal rate, and changes in the Mini-Mental State Examination (MMSE) and the cognitive subscale of the AD Assessment Scale (ADAS-cog) relative to baseline measurements. Research Article British Journal of Medicine & Medical Research, 3(2): 341-350, 2013 342 Results: Two patients were lost to follow up, and 122 patients completed the 18-month trial. The mean age of the participants was 65.3±6.4 years (range 54-82), and 77 (63.1%) of the participants were female. Improved cognitive function was observed in the first 6 months of the regimen (ADAS-cog=-3.1±10.1; MMSE=1.2±3.0), and the stabilisation of cognitive decline was observed over the remaining 12 months (ADAScog=-1.6±7.6; MMSE=0.8±4.2). AEs were predominantly gastrointestinal and occurred in 7.3% of patients. Conclusions: MLC601 showed good tolerability and promising effects on cognitive function in AD patients during 18 months of treatment.

Multiple sclerosis (MS) requires long-term therapy and can affect many aspects of a patient's life, including quality of life. MS patients score lower on health-related quality of life (HRQoL) measures. The efficacy of subcutaneous interferon (IFN) β-1a has been extensively evaluated by using objective measures but its impact on HRQoL is currently unclear. In this observational study, we evaluated HRQoL of Iranian patients with relapsing-remitting MS (RRMS) treated with IFN β-1a by using short-form 36 (SF-36) and multiple sclerosis international quality of life (MusiQoL) questionnaires.Four hundred recruited RRMS patients were treated with human serum album free IFN β-1a for 1 year. Patients were required to fill in SF-36 and MusiQoL questionnaires at the first visit and at each follow-up visit. Expanded disability status scale (EDSS) evaluation was performed at baseline and at each visit. Comparisons in HRQoL between visits were calculated using Cohen's d effect size. The relationship between change in EDSS score and the score of each questionnaire was calculated using Pearson correlation coefficients.Three-hundred and eighty three completed the study. Two-hundred and thirty nine were female. Mean (SD) age was 28.75 (±5.49). After 1 year, overall MusiQoL Index score effect size was -0.16 and SF-36 physical component and mental component showed overall effect sizes of -0.28 and -0.53, respectively. Mean (range) EDSS change was 1 (1-4). Three-hundred and seventy four were clinically stable with mean (range) EDSS change of 0.1 (-2-0.5). Increase in EDSS was linked to a decrease in both MusiQoL and SF-36.We found that, HRQoL did not change significantly over the first year of therapy. Furthermore, decreases in HRQoL were inversely correlated with increases in EDSS score.

Background: MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. Methods: In a multicenter, nonblinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. Results: There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). Conclusion: MLC601 showed a promising safety profile and also efficacy compared to 3 FDA-approved ChEIs.

A 75-year-old right-handed man was admitted to our emergency department complaining of recurrent episodes of involuntary ‘barking' within the past 12h. The episodes had occurred after an initial two-minute attack from sleep involving tonic contraction of the upper extremities and jaw locking. By the time of admission, the patient had had a total of at least 7–10 ‘barking' episodes, each lasting 30–45s. Seven months prior to his current admission, the patient had had a minor ischemic stroke causing mild left paresis, which had resolved completely. His awake EEG revealed a normal background pattern interrupted by runs of two per second slow waves mixed with low-voltage spikes in the left temporal lobe with a left mid-temporal emphasis. The patient was diagnosed with recurrent simple partial seizures, and treatment with intravenous valproic acid was initiated. He was discharged four days later without having experienced any further barking episodes. Atypical presentations of the epileptic seizures have been described in the literature, but ictal barking is very rare manifestation of epilepsy.

Objective: We compared postsurgical outcome of patients with intractable epilepsy between temporal and extratemporal lesions. Background The results of surgical treatment of epileptic seizures have gradually improved in the past decade, approaching 60% to 90% seizure-free outcome in temporal lobe epilepsy and 45% to 66% in extratemporal lobe epilepsy in most modern epilepsy centers. Design/Methods: Among 114 intractable epilepsy patients with localized epileptogenic zone according to surface EEG, LTM, fMRI and SPECT, 43 patients were considered for epilepsy surgery in Loghman hospital, Tehran, Iran. They were categorized to temporal and extratemporal lobe epilepsy. Two years outcome after surgery were evaluated using Engel classification and compared between aforementioned groups. Results: The mean age of patients at surgery was 23.8±10.3 years (range, 6-48 years). There were 23 male (53%) and 20 female patients (47%). Frequency distribution of seizure type was containing GTCS, CPS and others in 30%, 21% and 49%, respectively. Lesions were located in temporal and extratemporal in 19 (44%), 22 (51%) and 2 (5%), respectively. Outcome of surgery in temporal lesions was Engel Class I (10 case), Engel Class II (8 case) III (0 cases) or IV (1 case). In extratemporal lesions after surgery results were containing Engel Class I (11 case), Engel Class II (5 case) III (4 cases) or IV (2 case). There was no difference between two groups in Engel Class (p=0.093). Conclusions: About half of patients have been remained seizure free completely in our series. This result shows outcome of surgery in extratemporal lesions is as favorable as temporal ones. Disclosure: Dr. Amini Harandi has nothing to disclose. Dr. Sharifi has nothing to disclose. Dr. Shahmohammadi has nothing to disclose. Dr. Gharagozli has nothing to disclose. Dr. Pakdaman has nothing to disclose.