Fampridine in multiple sclerosis patients with acute phase of cervical transverse myelitis: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Fampridine is a potassium channel blocker drug used to improve walking ability in patients with multiple sclerosis (MS). We evaluated the effect of fampridine in patients with MS in the acute phase of transverse myelitis. METHODS: In a randomized, placebo-controlled trial, 30 patients who had their first episode of cervical myelitis with quadriparesis presentation, with the final diagnosis of MS, were randomly divided into two equal groups. The intervention group received intravenous methylprednisolone (IVMP) for 7 days plus fampridine. The placebo group received IVMP for 7 days plus placebo. To compare the treatment results, we compared the Barthel index (BI) scores of the groups at the start of the trial and the 21st day after the start of treatment. RESULTS: There was no significant difference in baseline characteristics between the intervention and placebo groups in terms of mean age, sex, and mean admission BI (p > 0.05). Mean (SD) admission BI in placebo and intervention groups was 27.20 (7.341) and 27.87(5.78), respectively (p = 0.784). The measured mean (SD) BI after treatment was 48.73 (15.54) in the placebo and 64.93 (11.81) in the intervention group (p = 0.003) after 3 weeks. CONCLUSION: Using fampridine plus IVMP in the acute phase of transverse myelitis in MS patients improved the disease's symptoms and increased the daily activity ability of patients.

Vascular Endothelial Growth Factor as a Predictive and Prognostic Biomarker for Multiple Sclerosis.

BACKGROUND: Growing bodies of evidence suggest that angiogenesis plays a crucial role in the development and progression of multiple sclerosis (MS). Vascular endothelial growth factor (VEGF) is one of the key factors involved in angiogenesis. Because of this importance, we investigated the serum levels of VEGF in MS patients according to their clinical phase and subtype of MS in this study. MATERIAL AND METHODS: This case-control study was done on 47 definite MS patients with the first clinical attack and 47 randomly selected individuals without any underlying inflammatory and autoimmune disease as the control group. The total serum VEGF level was measured from the subject's peripheral blood sample by ELISA during the first and second attacks of MS and 6 months after the first attack in the remission phase as well as the control group. In addition, the correlation between these variables and the influence of gender, age, and duration of the remission phase on such associations was evaluated by using the independent t test and Pearson's correlation coefficient. RESULTS: There was an increase in the serum level of VEGF in all phases of MS compared with non-MS individuals (p value <0.0001) and a significant correlation between the serum level of VEGF and the interval between first and second attacks (r = -720, p < 0.0001). A higher serum level of VEGF in the first attack leads to higher VEGF levels in the second and sixth mount of remission phases. CONCLUSION: Rise in the serum VEGF level may be involved in MS's relapsing phases and a shorter remission phase. Therefore, it could be used as a prognostic and predictive biomarker for MS disease.

SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group.

[Figure: see text].

A randomized double-blind trial of comparative efficacy and safety of Avonex and CinnoVex for treatment of relapsing-remitting multiple sclerosis.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Avonex and CinnoVex showed similar efficacy and safety outcome in patients with RRMS.

Health-related quality of life in patients with relapsing-remitting multiple sclerosis treated with subcutaneous interferon ß-1a in Iran.

PURPOSE: 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) ß-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 ß-1a by using short-form 36 (SF-36) and multiple sclerosis international quality of life (MusiQoL) questionnaires. METHODS: Four hundred recruited RRMS patients were treated with human serum album free IFN ß-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. RESULTS: 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. CONCLUSION: 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.

Vagus nerve stimulation in drug-resistant epilepsy: the efficacy and adverse effects in a 5-year follow-up study in Iran.

Drug-resistant epilepsy seems like a different disease compared with easy to control epilepsy, and new strategies are needed to help these patients. Vagus nerve stimulation (VNS) therapy is the most frequently used neurostimulation modality for patients with drug-resistant epilepsy who are not eligible for seizure surgery. In this study, we aimed to evaluate the efficacy and adverse effects of VNS in patients with drug-resistant epilepsy in an open-label, prospective, long-term study in Iran. We selected 48 patients with partial-onset drug-resistant epilepsy. Implantations were performed in the neurosurgery department of Loghman Hospital, Tehran, Iran. Follow-up visits were done on monthly bases for 5 years. Forty-four patients completed the study. Mean age of patients was 24.4 years. Mean years of epilepsy history was 14 years. The mean number of anti-epileptic drugs did not significantly change over five years (p = 0.15). There was no exacerbation of epilepsy; however, one patient discontinued his therapy due to unsatisfactory results. Five patient had more than 50 %, and 26 patients (59 %) had 25-49 % reduction in the frequency of monthly seizures persistently. Overall mean frequency of monthly seizures decreased by 57.8, 59.6, 65, 65.9, and 67 %, in 1st, 2nd, 3rd, 4th, and 5th years of follow-up, respectively. Most common side effects were as follows: hoarseness (25 %) and throat discomfort (10 %). We found VNS as a safe and effective therapy for drug-resistant epilepsy, with an approximate long-term decrease in mean seizure frequency of 57.8-67 %. Thus, VNS is recommended for suitable patients in developing countries.

The role of serum level of interleukin-6 in severity of pulmonary complications of sulfur mustard injuries.

Diverse studies suggest that interleukin-6 (IL6), as a member of cytokines family, has a major role in inflammatory processes of airways and lungs. In this study, an attempt was made to determine the serum level of IL6 in sulfur mustard (SM) injured patients and its comparison with controls. The measured IL6 mean level in patients with chemical injuries (0.76±0.3 ng/ml) was significantly higher than the control group's mean level (0.34±0.12 ng/ml). Furthermore, patients with moderate to severe symptoms had a serum level of (0.95±0.92 ng/ml) which was significantly higher than mild (0.47±0.54) and control (0.34±0.12) groups. The outcome of this research program demonstrates that an increase in serum level of IL6 can have a role in pulmonary complications of SM, similar to other well defined pulmonary diseases.  However, further studies are required to clarify the role and mechanism of IL6 in such patients.

A Long-term Study of NeuroAid (MLC601, MLC901) in Patients with Alzheimer's Disease; An Extension 8-year Follow-up Study.

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 < 0.001). 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.

MLC901 in hypoxic-ischemic brain injury patients: A double-blind, randomized placebo-controlled pilot study.

BACKGROUND: Hypoxic-ischemic brain injury (HIBI) is a disabling consequence of cardiopulmonary resuscitation, which has no direct treatment except supportive care. Many studies have used pharmacological agents to reduce or stop this disability. MLC901 is a traditional Chinese medicine showing neuroprotective and regenerative effects on focal and global ischemia in previous animal and human studies. We designed an experimental, randomized, double-blind, placebo-controlled study to analyze MLC901 efficacy in HIBI patients. METHODS: In a randomized, placebo-controlled trial, 35 patients with HIBI were randomly designated to receive either MLC901 or placebo capsules 3 times per day over 6 months. We assessed the 2 groups by modified Rankin Scale and Glasgow Outcome Scale at baseline, and follow-up visits in 3rd month, and 6th-month after injury. RESULTS: Thirty-one patients completed this study. There was no significant difference in baseline characteristics between the 2 groups as regards age, gender, time of resuscitation, the interval between injury and start of the intervention, and the length of intensive care unit stay. Both the placebo and intervention groups improved during the investigation. However, the Glasgow Outcome Scale and modified Rankin Scale scales were significantly improved in the MLC901 group compared to the placebo after 6 months (P < .05) with close to no adverse effects. No major side effect was reported. CONCLUSION: MLC901 has shown, compared to placebo, a statistically better improvement at 6 months in neurological functions of patients with HIBI.

Comprehensive Review on Neuro-COVID-19 Pathophysiology and Clinical Consequences.

Aside from the respiratory distress as the predominant clinical presentation of SARS-CoV-2 infection, various neurological complications have been reported with the infection during the ongoing pandemic, some of which cause serious morbidity and mortality. Herein, we gather the latest anatomical evidence of the virus's presence within the central nervous system. We then delve into the possible SARS-CoV-2 entry routes into the neurological tissues, with the hematogenous and the neuronal routes as the two utmost passage routes into the nervous system. We then give a comprehensive review of the neurological manifestations of the SARS-CoV-2 invasion in both the central and peripheral nervous system and its underlying pathophysiology via investigating large studies in the field and case reports in cases of study scarcity.

Balo's concentric sclerosis: an update and comprehensive literature review.

Balo's concentric sclerosis (BCS) is considered a variant of multiple sclerosis characterized by concentric lamella of alternating demyelinated and partially myelinated tissues. It is a rare and a relatively acute condition. Attacks may proceed rapidly over weeks or months, typically without remission, like Marburg's variant, resulting in death or severe disability. However, the majority of cases have a more benign, self-limiting course with spontaneous remission. Magnetic resonance imaging is a primary imaging modality in the diagnosis of BCS. Treatment with intense immunosuppression may be indicated in patients with more aggressive form. New reports reveal more evidence regarding the pathophysiology and treatment strategies.

Efficacy and Safety of MLC601 in Patients with Mild to Moderate Alzheimer Disease: An Extension 4-Year Follow-Up Study.

BACKGROUND AND AIM: Alzheimer disease (AD) is the most common cause of dementia. Currently, there is no disease-modifying therapy for AD. We aimed to evaluate the long-term efficacy and safety of MLC601 in the treatment of AD. METHODS: In this open-label extension study, patients with mild to moderate AD according to DSM-IV criteria were recruited. Patients received MLC601 capsules 3 times a day for 4 years. Cognitive function was assessed every 6 months using Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores. Safety profiles, including adverse events (AEs), and treatment-related abnormality in laboratory tests were also reported. RESULTS: Of a total of 122 patients, 105 completed the study. The mean age was 66.8 ± 6.3 years at the beginning of the study. Sixty-five (61.9%) were female. The mean (±SD) change in MMSE and ADAS-Cog scores at the end of the study was 2.1 (±3.8) and -5.1 (±8.7), respectively. Repeated measure analysis revealed a statistically significant change in both scores (p < 0.001). No patient left the study due to an AE. No abnormality was noted in lab tests. Gastrointestinal symptoms were the most commonly reported AEs. CONCLUSION: The efficacy of treating AD patients with MLC601 over 4 years has been demonstrated in the present study. Overall, it seems that the safety and efficacy of MLC601 is promising compared to currently prescribed treatments.

MLC601 in vascular dementia: an efficacy and safety pilot study.

BACKGROUND AND AIM: Vascular dementia (VaD) is the second most common cause of dementia and currently there is scarcity of therapies for VaD. We aimed to investigate the efficacy and safety of MLC601 in the treatment of VaD. METHODS: In this multicenter, pilot, randomized, double-blind trial, 82 patients with VaD according to DSM-5 criteria received MLC601 or placebo capsules three times a day for 2 years. The primary efficacy end-point was evaluated by comparing Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score between the two groups over 2 years of study. Safety was also assessed by recording adverse events and abnormal laboratory results. RESULTS: Eighty-one patients completed the study and were included in the analysis. One patient was lost to follow-up in the placebo group. After 2 years, mean (±SD) changes in the MMSE score were -3.71 (±4.50) for MLC601 group and -9.33 (±4.80) for placebo group. ADAS-cog score showed (±SD) changes of 7.34 (±9.55) and 19.00 (±11.28) for MLC601 and placebo group, respectively. Repeated measures analyses showed that both MMSE and ADAS-cog scores were significantly better in the treatment group at 24 months (p<0.001). Ten (24.39%) patients reported predominantly transient gastrointestinal adverse events in MLC601 group. No patient left the study due to adverse events. There were no clinically significant abnormalities on laboratory tests. CONCLUSION: Patients treated with MLC601 over the 2 years showed dramatically better cognitive outcome compared with those treated with placebo. MLC601 was devoid of any serious adverse events and was well-tolerated.

Efficacy and Safety of MLC601 in the Treatment of Mild Cognitive Impairment: A Pilot, Randomized, Double-Blind, Placebo-Controlled Study.

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.

Persian version of frontal assessment battery: Correlations with formal measures of executive functioning and providing normative data for Persian population.

BACKGROUND: Cognitive impairment in patients with Parkinson's disease (PD) mainly involves executive function (EF). The frontal assessment battery (FAB) is an efficient tool for the assessment of EFs. The aims of this study were to determine the validity and reliability of the psychometric properties of the Persian version of FAB and assess its correlation with formal measures of EFs to provide normative data for the Persian version of FAB in patients with PD. METHODS: The study recruited 149 healthy participants and 49 patients with idiopathic PD. In PD patients, FAB results were compared to their performance on EF tests. Reliability analysis involved test-retest reliability and internal consistency, whereas validity analysis involved convergent validity approach. FAB scores compared in normal controls and in PD patients matched for age, education, and Mini-Mental State Examination (MMSE) score. RESULTS: In PD patients, FAB scores were significantly decreased compared to normal controls, and correlated with Stroop test and Wisconsin Card Sorting Test (WCST). In healthy subjects, FAB scores varied according to the age, education, and MMSE. In the FAB subtest analysis, the performances of PD patients were worse than the healthy participants on similarities, fluency tasks, and Luria's motor series. CONCLUSION: Persian version of FAB could be used as a reliable scale for the assessment of frontal lobe functions in Iranian patients with PD. Furthermore, normative data provided for the Persian version of this test improve the accuracy and confidence in the clinical application of the FAB.

Efficacy of Tiotropium Bromide and Rehabilitation Treatment on Pulmonary Function of Patients With Sulfur Mustard Lung Injury.

BACKGROUND: Chronic pulmonary complication is the most common delayed toxic effect of sulfur mustard (SM) and it has no treatment so far. OBJECTIVES: To evaluate short-term therapeutic effects of inhaled tiotropium bromide and pulmonary rehabilitation on pulmonary function of patients with SM induced lung injury. PATIENTS AND METHODS: In a randomized clinical trial, using convenient sampling method, 54 patients with chronic lung disease due to SM exposure were recruited in Baqiyatallah General Hospital, Tehran, Iran for a period of 2-month study. They were randomly divided into 3 groups of 18 participants each. Group 1 received routine drugs (Serevent, Flixotide), pulmonary rehabilitation 30 minutes/2 times a week, and tiotropium bromide 18 µg/day. Group 2 was treated with routine drugs and pulmonary rehabilitation and group 3 was only on the routine drugs. cardiopulmonary exercise test (CPET), plethysmographic measurements, and respiratory symptoms evaluation were performed before and after medical intervention. RESULTS: In group 1, compared to group 3, significant differences were found with regard to symptoms of cough ([difference between the first and last visit in group 1: Diff 1] = -1.6, Diff 3 = -0.3, P = 0.01) and nocturnal dyspnea (Diff 1 = -1.9, Diff 3 = 0.0, P = 0.01), likewise, compared to group 2, significant differences were found with regard to lung function parameters of forced vital capacity (Diff 1 = 3.0, Diff 2 = -3.5, P = 0.03), forced expiratory volume in one second (Diff 1 = 3.9, Diff 2 = -5.6, P = 0.009), maximal mid-expiratory flow rate 25% - 75% (Diff 1 = 1.5, Diff 2 = -3.2, P = 0.007) and peak expiratory flow (Diff 1 = -2.06, Diff 2 = -4.3, P = 0.04). Total lung capacity (Diff 2 = 9.28, Diff 3 = -12.07, P = 0.02) and residual volume (Diff2 = 32.1, Diff3 = -27.6, P = 0.04) were increased in group 2 compared to group 3. There were no significant differences with regard to CPET results among all groups (P > 0.05). CONCLUSIONS: Inhalation of tiotropium bromide in combination with pulmonary rehabilitation could improve some plethysmographic lung volumes and clinical outcomes in patients with chronic pulmonary disease due to SM. Short-term prescription of pulmonary rehabilitation has no effect on CPET of patients.

Comparing efficacy and side effects of a weekly intramuscular biogeneric/biosimilar interferon beta-1a with Avonex in relapsing remitting multiple sclerosis: a double blind randomized clinical trial.

OBJECTIVE: We compared the efficacy and safety of two biosimilar forms of interferon beta-1a in the treatment of multiple sclerosis: Avonex (Biogen Idec, USA) and CinnoVex (CinnaGen, Iran). METHODS: In a double blind randomized clinical trial study 84 patients with relapsing remitting multiple sclerosis (RRMS) with Expanded Disability Status Scale (EDSS) score of 0-5.5 were randomly allocated to two groups of 42 subjects. RESULTS: Twenty-four patients lost to follow-up. Finally, 31 patients (mean±SD of age=33.7±7.0; 7 males and 24 females) in the Avonex and 29 patients (mean±SD of age=32.2±9.2; 8 males and 21 females) in the CinnoVex group completed full 24 months of study period. Decrease in EDSS was 1.05±0.24, p=0.62 in the Avonex and 0.16±0.88, p=1.0 in the CinnoVex group after 12 months and 0.27±1.05, p=0.46 in the Avonex and 0.16±1.06, p=1.0 in the CinnoVex group after 24 months. There was no statistically significant difference in attack number between two groups (1.0±1.2 in Avonex and 1.2±1.3 in CinnoVex; p=0.46). Volume of T2-weighted lesions on MRI showed a progressive significant increase in the 12th month (28056±23693) in Avonex treated patients compared with first image (16353±11172) (p=0.01). But number of gadolinium-enhancing lesions in CinnoVex showed statistically significant decrease after 12 months (0.08±0.28 vs. 1.00±1.22; p=0.03). However, there were no significant differences between groups after 24 months. There were no significant differences between 2 groups regarding frequency and duration of most considerable side effects, as well. Neutralizing antibodies were not positive in any patients. CONCLUSION: CinnoVex can be used as a safe and effective alternative to Avonex in treatment of RRMS.