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Medication adherence is of utmost importance in achieving the desired therapeutic outcome and effectively managing seizures in patients with epilepsy (PWE). It is imperative to recognize self-esteem as a psychological determinant that potentially influences the optimal compliance with anti-seizure medications (ASMs) among PWE. The objective of this study was to explore medication adherence and its relationship with self-esteem among individuals diagnosed with epilepsy in Isfahan, Iran., Methods: This descriptive-analytical study was conducted in the year 2021, encompassing a cohort of 250 PWE who were referred to designated medical facilities in Isfahan, Iran, and were selected by the consecutive sampling technique. A 3-part instrument including demographic components, the Rosenberg Self-Esteem Scale, and the Morissky Drug Adherence Questionnaire employed for data collection., Results: The mean and standard deviation of adherence to the medicinal regimen in the participants were 6.9 ± 2.02, and 46.4 % had a low level of adherence to the medication regimen (total score 0-6). At the same time, the mean and standard deviation of self-esteem in these patients was 5.11 ± 2.11. There was a statistically significant and direct correlation between adherence to the prescribed drug regimen and self-esteem (rs = 0.464, p = 0.00)., Conclusion: Based on the findings of the study that showed a statistically significant and positive correlation between self-esteem and adherence to the medication regimen, it is advisable to enhance and advocate for these factors in PWE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cerebellar ataxias are a wide heterogeneous group of disorders that may present with fine motor deficits as well as gait and balance disturbances that have a significant influence on everyday activities. To review the ocular movements in cerebellar ataxias in order to improve the clinical knowledge of cerebellar ataxias and related subtypes. English papers published from January 1990 to May 2022 were selected by searching PubMed services. The main search keywords were ocular motor, oculomotor, eye movement, eye motility, and ocular motility, along with each ataxia subtype. The eligible papers were analyzed for clinical presentation, involved mutations, the underlying pathology, and ocular movement alterations. Forty-three subtypes of spinocerebellar ataxias and a number of autosomal dominant and autosomal recessive ataxias were discussed in terms of pathology, clinical manifestations, involved mutations, and with a focus on the ocular abnormalities. A flowchart has been made using ocular movement manifestations to differentiate different ataxia subtypes. And underlying pathology of each subtype is reviewed in form of illustrated models to reach a better understanding of each disorder., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aim to evaluate the prevalence of depression in disorders including multiple sclerosis (MS), Parkinson's disease (PD), migraine, and stroke. Also, we detect risk factors for depression occurrence within each disorder. Moreover, we compare the risk factors in these four common neurologic disorders. In advance, we assess the three surveys in order to better comprehend their distinctions., Background: Depression is a globally prevalent Psychologic disorder and common co-morbidity in neurological diseases. However, it is mostly underdiagnosed in chronic patients and causes numerous adverse effects., Methods: We used the database of neurology specialty clinics in a hospital in Tehran, the largest city of Iran. Five hundred nineteen patients, including 105 PD patients, 101 patients with stroke, 213 cases with MS, and 100 Migraine patients, were assessed. They were asked about their chief characteristics and disease-specific variables that may cause depression. Moreover, depression criteria were measured with three internationally used scales to study their variances., Results: Overall, the prevalence of depression in PD, stroke, MS, and migraine, according to the BDI-II scale, were 43.8%, 38.6%, 45.1%, 37.6%, and according to HDRS scale, were 56.2%, 51.5%, 39.4%, and 43.6% respectively. Finally, according to DSM-XC the depression prevalence were 64.8%, 34.7%, 36.2%, and 67.3% respectively. Possible risk factors of depression were lower educational level, disease severity, socioeconomic level, marital or employment status, female gender, higher age, and consumption of some specific drugs., Conclusion: Depression is a widespread disorder in chronic neurologic conditions. Our data suggests the odds of depression in neurologic disorders depend on the characteristics of the patient and the features of the disease., Competing Interests: None., (© 2024 The Authors.)

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications., (© 2023. The Author(s).)

The neuroprotective effects of dietary patterns have been reported in previous studies. This study aimed to examine the association between the dietary approach to stop hypertension (DASH), the Mediterranean diet (MeDi), and the Mediterranean-DASH intervention for neurodegenerative delay (MIND) with the severity and risk of Parkinson's disease (PD). In this comparative cross-sectional study, 120 patients with PD and 50 healthy participants participated. Adherence to DASH, MeDi, and MIND dietary patterns was determined according to the dietary intake data using a food frequency questionnaire (FFQ). The Severity of PD was determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The mean score of the DASH was significantly lower in the PD group compared to the healthy group ( p  = .006), but the mean score of MeDi and MIND did not significantly differ between the two groups ( p  > .05). Also, the mean score of the DASH was significantly lower in men than in women in the healthy group ( p  = .018). High adherence to the DASH diet decreased the risk of PD by 15% (OR = 0.856, 95% CI: 0.751, 0.976, p  = .020). Participants in quartiles 3 and 4 of the DASH dietary pattern had 86% ( p  = .003) and 87% ( p  = .007), respectively, lower risk of PD. MeDi and MIND diets were not significantly associated with the risk of PD. There was no significant association between dietary patterns and the severity of PD. The findings indicate that high adherence to the DASH dietary pattern may protect against PD., Competing Interests: The authors declare that they do not have any conflicts of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Scarce data are available on the neurological presentations of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) and COVID-19-unrelated rhino-orbito-cerebral mucormycosis (ROCM). This study aimed to compare the neurological presentations and their associated outcomes in patients with CAM and COVID-19-unrelated ROCM. Methods: In December 2021, a case-control analysis was conducted on the CAM (case group) and COVID-19-unrelated ROCM (control group) referrals of one center in Isfahan, Iran. Confirmed CAM patients from January 2020 to December 2021 constituted the case group, and patients with COVID-19-unrelated ROCM from 2016-2019 constituted the control group. Their data were then analyzed using proper (non) parametric tests and generalized linear models (GLM), therein P-value below 0.05 was considered as the criterion of statistical significance, and the SPSS software was used. Results: After retrieving data on 177 patients with mucormycosis, 78 patients with CAM were included as the case group and 72 patients with COVID-19-unrelated ROCM were included as the control group. Neurological presentations suggestive of second, third, and eighth cranial nerve involvement were more prevalent in the CAM group (all with P < 0.05). The mortality rate in the CAM group was 1.9 times that of the controls (P = 0.01), being explained by higher extent of corticosteroid administration among them. Higher age and presentation with gait ataxia, ptosis, and mydriasis were considered to be predictive of poor prognosis in patients with CAM (all with P < 0.05). Conclusion: The neurological manifestations of CAM differ from COVID-19-unrelated ROCM based on the presented results, some of which are associated with poor prognosis. Further replication is warranted to confirm our retrospective analyses., Competing Interests: The authors declare no conflict of interest in this study., (Copyright © 2023 Iranian Neurological Association, and Tehran University of Medical Sciences Published by Tehran University of Medical Sciences.)

Background: Patients with multiple sclerosis (MS) often experience balance issues during physical activities. Traditional rehabilitation exercises such as stretching, resistance, and aerobic training have been found to be effective, but can be repetitive and tedious, leading to reduced patient motivation and adherence. Furthermore, direct supervision by a therapist is not always possible., Methods: The aim of this study was to develop and evaluate the effectiveness of a virtual training program incorporating visual feedback from the Kinect® sensor in male patients with multiple sclerosis. Forty-five participants, with an age range of 22-56 years (mean age = 39), were randomly assigned to one of three equal groups, including two experimental groups and one control group. The experimental groups participated in eight-week exercise interventions, with each session lasting 20 to 30 min and occurring three times per week. In contrast, the control group received no interventions. Within the experimental groups, one was exposed to conventional balance exercises, whereas the other engaged in the proposed virtual training program. Both of these groups undertook three balance exercises, namely the single-foot stance, lunge maneuvers, and arm/leg stretching routines. The assessment encompassed diverse facets of balance, including parameters of 10 Meter Walk Time, Berg Balance Scale, Static Balance Score, and Time-Up and Go Scale, as well as the quality of life, gauged through the Multiple Sclerosis Quality of Life (MSQOL)-54 Questionnaire. The effect of test variables was investigated using analysis of covariance (ANCOVA), while the independent samples t-test was used to check for significant differences among the groups. The effects of the groups were compared using a paired samples t-test., Results: The findings revealed that both rehabilitation programs positively affected the dependent variables compared to the control group. However, the significant difference between the pre-test and post-test scores of the experimental groups indicated the effectiveness of the proposed program compared to the traditional method., Conclusions: Entertaining virtual training programs utilizing visual feedback can be effective for rehabilitating patients with MS. The proposed method enables patients to perform rehabilitation exercises at home with high motivation, while accurate information about the treatment process are provided to the therapist., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Diagnosis of Parkinson's disease (PD) is associated with a vast number of challenges. This study aimed to assess the overlap of PD patients' transcriptomes in the substantia nigra (SN) with peripheral blood mononuclear cells (PBMCs) to discover potential biomarkers for diagnosis., Methods: GEO data were used to select genes with significant changes in expression level in the SN region and eligible studies. Also, transcriptome data related to blood of PD patients with other neurodegenerative diseases (ND) was considered. Differential expression genes between PD and control were evaluated in the SN and blood, and RT-qPCR was applied to validate the findings., Results: At the expression level, no significant similarity in long non-coding RNA was found between the patients' SN and blood. While in silico results revealed 16 common mRNAs in SN and blood with significant expression levels. Among all overexpressed mRNAs, HSPA1A/B expression level had the highest expression difference between control and PD samples. Moreover, DGKH had the highest score of down-regulated genes in both blood and SN. The NOTCH pathway had the highest score pathway among up-regulated pathways, and the expression levels of NOTCH2, H4C8, and H2BC21 associated with this pathway had the most ability to separate the control and PD populations. Furthermore, RT-qPCR results revealed that HSPA1A/B, NOTCH2, and H4C8 were overexpressed in PD PBMCs, while DGKH expression levels were lower compared to controls., Conclusion: Our findings indicate that expression levels of HSPA1A/B, DGKH, and NOTCH2 could be applied as candidate biomarkers to diagnose PD patients in the SN region and PBMCs., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Several etiologies are responsible for presentation of a twitching tongue in clinical practice. Some of these etiologies cause an isolated hyperkinetic tongue muscle, and some others cause it along with other signs and symptoms., Objectives: The present paper aims to review the causes, pathology, and presentations reported with twitchy tongue. An anatomical basis of the etiologies responsible for presentation of a twitchy tongue and hyperkinetic movement disorders of this muscle is pursued., Method: The reporting of this systematic review was guided by the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement. All of the research papers conducted with keywords described in the method section between 2000 and 2022 were used, and review articles and articles without any human subject and without any described hyperkinetic movement disorders of the tongue were excluded., Results: All of the etiologies responsible for hyperkinetic movement disorders of tongue were listed in the basis of their anatomical site of effect; cortical region, basal ganglia, cerebellum, brain stem, nucleus and nerve, and neuromuscular junction. One last remained part is the "not classified" section, which contains the etiologies with no particular anatomical origin., Conclusion: There are a variety of responsible etiologies for presentation of a twitchy tongue, and in the matter of a complaint of hyperkinetic tongue presentation, physicians should consider anatomical, functional, and psychological etiologies and other signs and symptoms must be participated in the diagnosis process to achieve a proper medical decision., (© 2023. Fondazione Società Italiana di Neurologia.)

Multiple sclerosis (MS) is an immune system-mediated neurodegenerative disease. Recent studies suggest that viral agents, especially the Epstein Barr virus (EBV), are etiological agents for MS. The roles of other viruses in MS have been investigated. Studies have shown an increase in the level of antibodies against bovine leukemia virus (BLV) in patients with MS. In this regard, our study aimed to examine the presence of BLV DNA in peripheral blood mononuclear cells (PBMCs) of MS patients in Iran. In this cross-sectional study, the presence of BLV in 109 Iranian MS patients and 60 healthy controls was evaluated. The isolated PBMCs were used for DNA extraction and PCR, using specific primers for two distinct genes. The mean age of the participants was 39 ± 9.5 years, and 27 (24.77%) of them were male. Clinical evaluation of these patients showed the most frequent MS type to be relapsing-remitting MS (RRMS) (71; 65.14%). BLV evaluation did not show any BLV DNA presence in the PBMCs of individuals in either the MS or healthy control groups. Therefore, our study showed no evidence of BLV infection in Iranian MS patients., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.)

Neurotuberculosis is a potentially fatal disease that can present with upper or lower motor neuron symptoms. Longitudinally extensive transverse myelitis (LETM) is characterized by contiguous inflammatory lesions of the spinal cord extending to three or more vertebral segments. The causes of LETM include infections, neoplasm, and autoimmune diseases. Mycobacterium tuberculosis is a rare cause of transverse myelitis. Here, we report a 21-year-old Afghan female who was referred with chronic progressive quadriparesis and showed LETM on cervical MRI. This report indicates that tuberculosis should be considered as a differential diagnosis of LETM, especially in endemic areas.

In recent decades, multiple sclerosis (MS) diseases have been significantly prevalent in some industrial areas of Iran, such as steel industrial areas in Isfahan province (central Iran). In this study, the environmental impacts of two steel mill factories in Isfahan province and their effects on the spread of MS in the region were investigated. To examine the extent of exposure, seasonal dust samples were collected from 15 sites around the two investigated factories. The annual dust deposition rate (DDR) was then determined and the concentrations of lead (Pb), cadmium (Cd), nickel (Ni), cobalt (Co), and manganese (Mn) in the dust samples were measured. Furthermore, the concentration of the mentioned elements was determined in the nail samples taken from 40 MS patients and 40 healthy people (control) living in the study region. The interpolated map extracted from the DDR values showed the highest dust deposition around the two studied steel factories, which decreases with increasing distance from them. The enrichment factor (EF) of heavy metals was the highest at the distance between the two steel factories, decreasing by moving away from them which indicate that these two steel factories are the source of investigated heavy metals in the region. The statistical analysis also revealed significant differences (P < 0.01) between the concentration of heavy metals measured in nail samples taken from MS patients and healthy people. The mean Pb concentration measured in the nail sample taken from MS patients was more than 18 times that of healthy people (93.45 and 5.02 mg/kg, respectively). These results revealed a buildup of heavy metals in the body of MS patients much more than usual, originating from the activities of two investigated steel companies in the region., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: People with multiple sclerosis (pwMS) on anti-CD20 therapies (aCD20) and fingolimod have shown inadequate humoral responses to COVID-19 vaccines., Objective: The objective of the study was to pilot larger studies by demonstrating the safety and comparing the immunogenicity of different types of third doses in seronegative pwMS after two doses of BBIBP-CorV inactivated vaccine., Methods: In December 2021, subject to receiving their third dose, being COVID-19-naiive, and receiving no corticosteroid within two months, we measured the level of anti-SARS-CoV-2-Spike IgG in pwMS seronegative after two shots of BBIBP-CorV inactivated vaccine., Results: We included 20/29 pwMS who received adenoviral vector (AV), 7/29 who received inactivated, and 2/29 who received conjugated third doses. No serious adverse events were reported two weeks post-third dose. The pwMS receiving AV third doses showed significantly increased IgG concentrations, while only the ones not on aCD20 and fingolimod responded to inactivated third doses. An ordinal logistic multivariable generalized linear model indicated that age (per year β: -0.10, P = 0.04), type of disease-modifying therapy (aCD20 β: -8.36, P <0.01; fingolimod β: -8.63, P = 0.01; others: reference), and type of third dose (AV or conjugated β: 2.36, P = 0.02; inactivated: reference) are predictive of third dose immunogenicity among pwMS who remain seronegative after two shots of BBIBP-CorV vaccine. Statistical significance was not achieved for variables sex, MS duration, EDSS, duration of DMT, duration of third dose to IgG test, and duration from last aCD20 infusion to third dose., Conclusion: This preliminary pilot study highlights the need for further research to determine the optimal COVID-19 third dose vaccination strategy for pwMS living in areas where BBIBP-CorV vaccine has been used., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sedaghat, Etemadifar, Lotfi, Sayahi, Chitsaz, Salari and Ghasemi Movaghar.)

Metronidazole is a common and widely used antibiotic to treat a wide range of infectious diseases and has been associated with serious neurologic disturbances which in some cases were irreversible. We present a metronidazole-induced encephalopathy in a 19-year-old girl after 7 days of metronidazole treatment, with diffusion restricted subcortical white matter lesions along with the corpus callosum involvements. Diverse clinical presentation of a serious neurologic disturbance caused by a common widely used antibiotic should be carefully addressed in the setting of both short- and long-term treatment.

Background: Immunogenicity data shows blunted responses to COVID-19 vaccination among people with MS (pwMS) on certain disease-modifying therapies (DMTs). Still, it is uncertain how this data translates into the clinic., Objective: To assess the effect of DMTs and other factors on the effectiveness of inactivated vaccination in pwMS., Methods: This cohort study was conducted in a period in which Iran experienced two COVID-19 peaks caused by the Delta variant. We used multivariable cox regression to compare COVID-19-free survivals, and an ordinal logistic model to compare COVID-19 severity between vaccinated pwMS on different DMTs., Results: A total of 617 pwMS were included in the final analysis, with a mean [SD] follow-up of 25.59 weeks [5.48] after their second dose. Laboratory/imaging-confirmed breakthrough COVID-19 occurred in 15/277 (5.41%) of injectable-treated (reference), 10/61 (16.39%) of fingolimod-treated (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 2.80 [1.24, 6.29]; P = 0.01), 9/128 (7.03%) of other oral-treated (aHR [95%CI]: 1.16 [0.50, 2.68]; P = 0.73), 19/145 (13.10%) of anti-CD20-treated (aHR [95%CI]: 2.11 [1.05, 4.22]; P = 0.04), and 6/56 (10.71%) of non-treated pwMS (aHR [95%CI]: 1.52 [0.57, 4.04]; P = 0.40). Age (adjusted Odds Ratio [aOR] [95%CI]: 1.05 [1.00, 1.10], P = 0.05) number of comorbidities (aOR [95%CI]: 2.05 [1.06, 3.96], P = 0.03), fingolimod therapy (aOR [95%CI]: 10.39 [2.47, 43.62], P < 0.01), and anti-CD20 therapy (aOR [95%CI]: 4.44 [1.49, 13.23], P < 0.01) were independently associated with a more severe COVID-19 course., Conclusion: The observed results stress the importance of developing personalized vaccination schedules and reservation of COVID-19 treatment resources for older pwMS with comorbidities receiving fingolimod or anti-CD20 therapies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Dysphagia as a consequence of multiple sclerosis (MS) puts individuals at higher risk of dehydration, malnutrition, and aspiration pneumonia. This study intended to investigate the effects of a combined program of neuromuscular electrical stimulation (NMES) and conventional swallowing therapy to improve swallow safety and efficiency, oral intake, and physical, emotional, and functional impacts of dysphagia in people with dysphagia and MS., Methods: In this single-case experimental study with ABA design, two participants with dysphagia caused by MS underwent 12 sessions therapy during 6 weeks following a baseline of 4 evaluation sessions. They were evaluated 4 more times in the follow-up phase after therapy sessions. Scores of Mann Assessment of Swallowing Ability (MASA), DYsphagia in MUltiple Sclerosis (DYMUS), and timed test of swallowing capacity were obtained at baseline, during treatment, and in the follow-up phases. The Dysphagia Outcome and Severity Scale (DOSS) based on videofluoroscopic swallow studies, Persian-Dysphagia Handicap Index (Persian-DHI), and Functional Oral Intake Scale (FOIS) were also completed before and after treatment. Visual analysis and percentage of nonoverlapping data were calculated., Results: MASA, DYMUS, FOIS, and DHI scores indicated significant improvement in both participants. Although the scores of the timed test of swallowing capacity in participant 1 (B.N.) and DOSS in participant 2 (M.A.) showed no changes, considerable improvements including reducing the amount of residue and the number of swallows required to clear bolus were seen in the posttreatment videofluoroscopic records of both participants., Conclusion: NMES in conjunction with conventional dysphagia therapy based on motor learning principles could improve the swallowing function and decrease disabling effects of dysphagia on different aspects of life in participants with dysphagia caused by MS., (© 2023 S. Karger AG, Basel.)

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a relatively unknown autoimmune entity. Scant reports of post-infection/vaccination anti-NMDAR encephalitis exist. We, hereby, reviewed the relevant cases and added to the literature a possible case of anti-NMDAR encephalitis following COVID-19 vaccination with BBIBP-CorV (Sinopharm). A 50-year-old Persian woman with previously known rituximab-treated MS presented complaining of worsening neurological symptoms all gradually starting and worsening after receiving the second dose of BBVIP-CorV 2 weeks before. Notable findings in her physical examination included ataxic gait and Babinski sign. Considering an acute MS relapse, corticosteroid pulse therapy was initiated, and she was referred for MRI, which revealed multiple new plaques. Her serum sample interestingly tested positive for anti-NMDAR antibodies. CSF analysis was unfortunately not performed. She responded well to the corticosteroid pulse therapy and showed substantial resolution of the symptoms. Considering its relatively low cost of workup and the benefits of correct early diagnosis, clinicians are advised to consider autoimmune encephalitis encountering patients with progressive neurological symptoms after the administration of vaccines, including the ones for COVID-19 which are currently being used extensively.

To affirm the short-term safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among people with multiple sclerosis (pwMS), 517 vaccinated and 174 unvaccinated pwMS were interviewed. 16.2% of the vaccinated pwMS reported at least one neurological symptom in their respective vaccine-related at-risk periods (ARP) - a period from the first dose until two weeks after the second dose of the vaccine. In a multivariable logistic regression model, the presence of comorbidities ( P  = 0.01), use of natalizumab ( P  = 0.03), and experiencing post-vaccination myalgia ( P  < 0.01) predicted the development of post-vaccination neurological symptoms. One MS relapse, one COVID-19 contraction, and one ulcerative colitis flare after the first dose, and four MS relapses after the second dose of the vaccine were the only reported serious adverse events during the ARPs. To show if the vaccine provoked MS relapses, we compared the relapse rate of vaccinated pwMS in the vaccine-related ARP with the annualized relapse rate of unvaccinated pwMS in the prior year-a measure of baseline MS relapsing activity in the respective time-using a multivariable Poisson regression model accounting for possible confounders, which failed to show any statistically significant increase ( P  = 0.78). Hence, subject to replication-as the vaccinated and unvaccinated pwMS differed in baseline characteristics-the BBIBP-CorV vaccine does not seem to affect short-term MS activity. Furthermore, as 83.33% of the unvaccinated pwMS reported fear of possible adverse events to be the reason of their vaccination hesitancy, provision of evidence-based consultations to pwMS is encouraged. Limitations of our study briefly included lack of data for self-controlled analysis of relapse rates, possible presence of recall bias, and lack of on-site validations regarding the clinical outcomes due to the remote nature.

Fingolimod (FTY720) is a drug derived from the fungicidal compound myriocin. As it was unclear whether FTY720 has antifungal effects as well, we aimed to characterize its effect on Candida albicans in vitro and in a mouse candidiasis model. First, antifungal susceptibility testing was performed in vitro. Then, a randomized, six-arm, parallel, open-label trial was conducted on 48 mice receiving oral FTY720 (0.3 mg/kg/day), intraperitoneal C. albicans inoculation, or placebo with different combinations and chorological patterns. The outcome measures of the trial included serum concentrations of interleukin-10 and interferon-gamma, absolute lymphocyte counts, and fungal burden values in the mice's livers, kidneys, and vaginas. Broth microdilution assay revealed FTY720's minimum inhibitory concentration (MIC99) to be 0.25 mg/mL for C. albicans. The infected mice treated with FTY720 showed lower fungal burden values than the ones not treated with FTY720 (p<0.05). As expected, the mice treated with FTY720 showed a less-inflammatory immune profile compared to the ones not treated with FTY720. We hypothesize that FTY720 synergizes the host's innate immune functions by inducing the production of reactive oxygen species. Further studies are warranted to unveil the mechanistic explanations of our observations and clarify further aspects of repurposing FTY720 for clinical antifungal usage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Najarzadegan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups., Competing Interests: Declaration of interests AP received grant support for remyelination trials in multiple sclerosis to the Amsterdam University Medical Centre, Department of Neurology, MS Centre (RESTORE trial), and UCL, London RECOVER trial; received grant fees from Fight for Sight (nimodipine in optic neuritis trial); received royalties or licenses from Up-to-Date (Wolters Kluwer) for a book chapter; received speaker fees for the Heidelberg Academy; participates on advisory board for SC Zeiss OCTA Angi-Network, and the SC Novartis OCTiMS study; holds leadership roles for governing board IMSVISUAL; was chairman of ERN-EYE Neuro-ophthalmology (until Oct, 2020); is board member of National Dutch Neuro-ophthalmology Association; received equipment from OCTA from Zeiss (Plex Elite); and received medical writing support from Novartis for a manuscript (https://doi.org/10.1002/acn3.51473). CF received consulting fees from Invex Therapeutics; received speaker honoraria from University of Dunedin; and holds leadership as Director of Royal Australian and New Zealand College of Ophthalmologists. VB received personal fees as consultant for Gensight and Neurophoenix. PC obtained grants from Annexon, Biogen, Genentech; received royalties from Cambridge Press for an OCT book; received consulting fees from Disarm Therapeutics, Nervgen, Biogen, Avidea; received honoraria from NY Academy of Sciences; and received equipment from Myelin Repair Foundation, Academic CME, Neuraly, and Landos. FC received speaker honoraria from Alexion, Accure Therapeutics, and the Sumiara Foundation. RDe obtained consulting fees from Alexion. JdS received consulting fees from Biogen, Teva, BMS Celegen, Roche, Novartis, Janssen, Merck, Alexion, CSL Behring; and honoraria from Biogen, Teva, BMS Celegen, Roche, Novartis, Janssen, Merck, Alexion, and CSL Behring. JFR received consulting fees from Roche, and Sanofi. EF holds honoraria from Alexion, Genzyme, Biogen, Novartis, and Janssen. TF holds honoraria from Alexion. CFT received honoraria from Novartis; and received support for attending meetings and travel from Novartis and Teva. KF obtained grants from Ministry of Education, Science and Technology of Japan as well as the Ministry of Health, Welfare and Labor of Japan; received consulting fees from Alexion Chugai-Roche Mitsubishi Tanabe, Novartis, Biogen, Eisai, Takeda, Teijin, Viela Bio, UCB, Merck, Japan Tobacco Pharma, and Abbvie; received honoraria from Alexion, Chugai-Roche, Mitsubishi Tanabe, Novartis, Biogen, Eisai, Takeda, Asahi Kasei Medical, Teijin, and Bayer; participated on a data safety monitoring board or advisory board from Alexion, Chugai, Mitsubishi Tanabe, Novartis, Biogen, Eisai, Takeda, Asahi Kasei Medical, Teijin, UCB, and Viela Bio; and received medical writing support from Oxford PharmaGenesis and Apothecom. RG acquired personal fees for participation on data safety monitoring boards, and served on the advisory boards for Biogen, Hikma, Merck, Roche, and Sanofi as well as receiving a grant from Roche. FG received grants or contracts from Roche (NMO epidemiologic studies) and Novartis (MS epidemiologic studies); received honoraria from for lectures from Roche, Novartis, Stendhal, and Merck; received support for attending meetings from the European Charcot Foundation, and ECTRIMS; and reports leadership of FOCEM (Foro Centroamericano y del Caribe de la Esclerosis Múltiple y otras enfermedades desmielinizantes del Sistema Nervioso Central) and Academia Panameña de Medicina y Cirugía (both unpaid). MHab obtained honoraria from Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva-Teva, Roche, and Zentiva; received support for attending meetings from Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva-Teva, and Roche; and participated on advisory board for Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva-Teva, and Roche. ZIl obtained grants or contracts from Biogen and Alexion; received honoraria from Biogen, Novartis, Roche, Merck, and Alexion; received payment for expert testimony from Roche; received support for attending meetings and travel from Biogen and Sanofi; and participated on a data safety monitoring board or advisory board from Biogen, Novartis, Merck, Sanofi, Roche, and Alexion. HJK received grants or contracts from National Research Foundation of Korea, Aprilbio, and Eisai; received consulting fees from Aprilbio, Daewoong, HanAll BioPharma, MDimune, Roche, Sanofi Genzyme, Teva-Handok, UCB, and Viela Bio; and received honoraria from Alexion, Biogen, Celltrion, Eisai, GC Pharma, Merck Serono, Novartis, Sanofi Genzyme, and Teva-Handok. RM received consulting fees from UCB, Alexion, Merck, Viela Bio, Novartis, and Roche; and participated on an advisory board for Viela Bio and Roche. FP obtained research support from Alexion; received grants or contracts from German Ministry for Research Support Recipient Charité Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Einstein Foundation, Guthy Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck, Serono, Novartis, Bayer, Roche, Parexel, and Almirall; received honoraria from the Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene; received support for attending meetings from Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Alexion, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene; participated on an advisory board for Celgene, Roche, UCB, Merck; and reports leadership as academic editor for Plos One, and associate editor for Neurology, Neuroimmunology, and Neuroinflammation. MBR received support for attending meeting from Novartis. BSD received consulting fees from Chiesi; received honoraria from Chiesi and Sanofi; received support for attending meetings from Bausch + Lomb; participated on an advisory board for Chiesi; and has stock options from Accure Therapeutics. DS received grants or contracts from National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), American Academy of Neurology (AAN), National Institute of Aging (NIA), National Multiple Sclerosis Society (NMSS), and United States Department of State; and was a committee member for Multiple Sclerosis International Federation (MSIF) and American Neurological Association (ANA). AS received grants or contracts from the Turkish MS society, and Istanbul University Research Support Grants; received consulting fees from Roche, Merck Serono, Biogen, Gen Pharma of Türkiye, Sanofi Genzyme, and Novartis; received honoraria from Sanofi Genzyme, Novartis, Roche, and Teva; and received support for attending meetings from Sanofi Genzyme. VvP obtained grants or contracts from Biogen; received consulting fees from Biogen, Merck, Sanofi, BMS, Novartis, Janssen, Almirall, and Roche; received honoraria from Biogen, Merck, Sanofi, BMS, Novartis, Roche; and received support for attending meetings from Biogen, Roche, and Almirall. MPW received royalties from Springer Healthcare and Elsevier; received consulting fees from Biogen, Roche, Biologix, Novartis, BMS-Celgene, Imcyse, Merck Serono, Sanofi Aventis, IXICO, and Icometrix; received honoraria from Bayer, Biogen, Biologix, Genilac, Novartis, Medison, Merck Serono, Roche, Sanofi Aventis, and BMS-Celgene; and participated on a data safety monitoring board for VU University Medical Center. LB received consulting fees as editor for the Journal of Neuro-Ophthalmology. GTP is an Emeritus editor for Neuro-ophthalmology. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Multiple sclerosis (MS) can present with facial symptoms and signs, such as facial palsy, myokymia, and hemifacial spasm. Considering the importance of early diagnosis, treatment, and exclusion of causes other than MS, we aimed to assess the prevalence of these disorders in patients with MS., Methods: MS patients who were referred to the Isfahan MS clinic from March 2021 to March 2022 were observed for facial presentations of the disease. A checklist of patients' baseline characteristics and disease features were then completed through patient interview and medical files., Results: Of the total of 2260 MS patients who were assessed, 3.27% had facial palsy, 1.28% had myokymia, and 0.84% presented with hemifacial spasm. The mean age of facial symptom onset was 30.74, 29.07, and 31.37 years, respectively. No relationship was found between the type of facial presentation and factors such as age, gender, subtype of MS, affected side of face, and time of presentation., Conclusion: On the grounds that facial disorders can be the first presentation of MS, patients with atypical features of other common facial diseases such as Bell's palsy should therefore be carefully assessed and followed for any clues pertaining to the diagnosis of MS., Competing Interests: Declaration of Competing Interests None., (Copyright © 2022. Published by Elsevier B.V.)

Competing Interests: The authors declare no conflict of interest in this study.

Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines' immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS-although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters' immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20-unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diencephalic region of the brain harbors sites with a considerable amount of aquaporin-4 expression. Neuromyelitis optica spectrum disorder (NMOSD) primarily involves autoimmune processes against this molecule. However, little is known about the frequency of symptoms of diencephalic involvement in NMOSD patients., Objective: To investigate the frequency of symptoms of diencephalic involvement in NMOSD patients and describe the associated characteristics in patients presenting such symptoms., Materials and Methods: This retrospective cohort included 145 NMOSD patients (39 males and 106 females) who visited Isfahan Multiple Sclerosis Center from January 2013 to February 2020 for approximately 61 months. Demographic and clinical information of patients and findings from radiological and serological investigations were retrieved., Results: The frequency of diencephalic involvement in NMOSD patients was 3.4% (five cases). Diencephalic syndrome-associated symptoms observed in this cohort consisted of narcolepsy (n = 2; 40%), hypotension (n = 1; 20%), amenorrhea (n = 1; 20%), and syndrome of inappropriate antidiuretic hormone secretion (n = 1; 20%). These manifestations responded well to NMOSD-associated treatments, i.e., rituximab and azathioprine., Conclusion: Although rarely manifested through symptoms suggestive of diencephalic involvement, NMOSD should be considered when encountering patients with the diencephalic syndrome to identify the primary cause of these manifestations., (© 2021. Belgian Neurological Society.)

Background: Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system that affects the patients' quality of life. This research was conducted with the aim of identifying the barriers of quality of life in patients with MS., Methods: This qualitative study was conducted through a conventional content analysis approach. We used the purposeful sampling with maximum diversity in terms of gender, age, education, marital status and employment. Data were collected through semi-structured interviews with 18 patients with multiple sclerosis referred to the MS Association of Isfahan. Interviews were conducted to the point of information saturation., Results: Through the content analysis of the interviews, we identified 2 main categories and 11 sub-categories. The main categories include intrapersonal problems (physical problems, psychological disorders, turbulent future, functional limitations, job loss and pennilessness), and environmental barriers (disease and treatment process, fatigue of caregivers, information deficiency about MS, family tensions, lack of social support and fun and entertainment)., Conclusions: In order to improve the quality of life in these patients, there is a need for attention and practical measures in the field of identified factors. By removing barriers such as providing educational and counseling services to the patients and their families, adapting the urban structure, providing financial support and adequate insurance coverage, the authorities can take measures to ensure patients' health and improve their quality of life., (© 2022. The Author(s).)

Objectives: Differentiating neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) from multiple sclerosis (MS) is important since MS therapies might result in progression and relapse of the former diseases. Evidence of long extending transverse myelitis (LETM) in magnetic resonance imaging (MRI) is one of the requirements to make an NMOSD diagnosis. However, centrally located lesions on spinal MRI may bring higher sensitivity and specificity to the NMOSD and MOG-AD diagnosis., Methods: We aimed to assess the association between NMOSD diagnosis and the presence of centrally located lesions at disease onset. We reviewed 102 medical records from the Isfahan MS clinic who presented with cervical cord lesions and 17 MS, 23 NMOSD, and 6 MOG-AD patients were selected. We collected demographic, clinical, and MRI data of patients who had clinical presentations of cervical cord lesion at disease onset, and the characteristics of the lesion were studied., Results: There was an association between NMOSD diagnosis and presence of a centrally located lesion (CLTM) (P < 0.001), presence of an LETM (P < 0.001), and an intermediate to high axial cord expansion (P < 0.001). CLTM and LETM can also be found in MOG-AD patients. The presence of CLTM (sensitivity and specificity: 95.65% and 69.56%), possessed higher sensitivity and specificity for NMO diagnosis than LETM presence (sensitivity and specificity: 78.26% and 43.47%)., Conclusion: A diagnostic criteria including the centrality, location, and expansion of the transverse myelitis lesions, in addition to LETM, may be more accurate in the diagnosis of NMOSD and MOG-AD and their distinction from MS., (Copyright © 2022. Published by Elsevier B.V.)

Background: Sacroiliac pain is one of the causes of low back pain, representing with discomfort and tenderness in the sacroiliac joint. Interventional procedures might be beneficial in cases unresponsive to medical treatments. Here, we aimed to investigate the effects of intra-articular corticosteroid injections in patients with sacroiliac pain., Materials and Methods: This is a clinical trial performed in 2017-2018 in Kashani Hospital, Isfahan, on patients with low back pain and formerly diagnosed with sacroiliac pain. Patients were recruited based on inclusion and exclusion criteria. Corticosteroid injections were performed for patients. Patients were visited within 2 weeks, 4 weeks, and 6 months after interventions, and pain and disabilities of patients were assessed using the numerical rating scale (NRS) and Oswestry Disability Questionnaire., Results: A total number of 27 patients entered our clinical trial. We showed that the mean NRS score among patients before interventions was 8.01 ± 0.96. Assessments of disability score also indicated that the mean disability scores was 41.48 ± 7.48. Our data also indicated that there was a significant reducing trend in both NRS and disability score after interventions ( P < 0.001 for both items)., Conclusion: Intra-articular steroid injection is associated with significantly reduced pain and disability in patients with sacroiliac pain. Previous studies evaluated variable methods and reported that this method has high values and significant advantages compared with other techniques which were in line with our results., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Advanced Biomedical Research.)

Background: Some current evidence is pointing towards an association between COVID-19 and worsening of multiple sclerosis (MS), stressing the importance of preventing COVID-19 among people with MS (pwMS). However, population-based evidence regarding the long-term post-COVID-19 course of relapsing-remitting multiple sclerosis (RRMS) was limited when this study was initiated., Objective: To detect possible changes in MS clinical disease activity after COVID-19., Methods: We conducted an observational study from July 2020 until July 2021 in the Isfahan MS clinic, comparing the trends of probable disability progression (PDP) - defined as a three-month sustained increase in expanded disability status scale (EDSS) score - and relapses before and after probable/definitive COVID-19 diagnosis in a cohort of people with RRMS (pwRRMS)., Results: Ninety pwRRMS were identified with definitive COVID-19, 53 of which were included in the final analysis. The PDP rate was significantly (0.06 vs 0.19, P = 0.04), and the relapse rate was insignificantly (0.21 vs 0.30, P = 0.30) lower post-COVID-19, compared to the pre-COVID-19 period. The results were maintained after offsetting by follow-up period in the matched binary logistic model. Survival analysis did not indicate significant difference in PDP-free (Hazard Ratio [HR] [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse-free (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36) survivals between the pre- and post-COVID-19 periods. Sensitivity analysis resulted similar measurements, although statistical significance was not achieved., Conclusion: While subject to replication in future research settings, our results did not confirm any increase in the long-term clinical disease activity measures after COVID-19 contraction among pwRRMS., (© 2022. The Author(s).)

Parkinson disease (PD) is the second most common neurodegenerative disease; the evidence suggests that lncRNAs and miRNAs play an important role in regulating the PD-related genes. The purpose of this research was to introduce two novel lncRNAs as the biomarker of PD diagnosis and treatment. We evaluated the expression profiles of six nodes of two regulatory networks in the PBMCs which had been got from 38 PD patients and 20 healthy individuals by qRT-PCR. Then, we compared the expression of these RNAs in both early and late stages of PD with the controls to determine if their expression could be related to the severity of disease. Further, this study investigated the direct interaction between one of the lncRNAs and target miRNA by using the dual luciferase assay. The results of the expression profiles of six nodes of the two ceRNA networks shown that linc01128, hsa-miR-24-3p and hsa-miR-30c-5p expression were significantly downregulated. While, the Linc00938, LRRK2 and ATP13A2 expression were up-regulated in the PBMC of the PD patients, in comparison to the controls. In addition, this study demonstrated that linc00938 directly sponged hsa-miR-30c-5p. The present study, therefore, for the first time, revealed two candidate lncRNAs as the biomarkers in the PD patients., (© 2022. The Author(s).)