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Extracurricular activities (ECA) are part of students' everyday life; they play important roles in students' lives. Few studies have addressed the question of how student engagements to ECA affect student's grade point average (GPA). This research was conducted to know whether the students' grade point average in King Abdulaziz University, Faisaliah campus is affected by their participation in the ECA. This study also studied the students' satisfaction on ECA. The study sample includes 239 students chosen via simple random sampling method. The study used inferential statistics to analyze this study design. To achieve the purpose of this study, a questionnaire (comprising 19 questions) was designed. The results showed that participation in ECA affects the students' GPA in a positive way. The study found that those who participated in ECA have higher GPA than those who did not; the study also found that the time spent participating in ECA did not affect the time students usually spend on studying (the result showed there wasn't any relationship between them). Furthermore, the study showed that students, based on faculty, are generally satisfied with the available extracurricular activities in the campus.

Ahmed M Al-Wathinani,1 Yahia O Dhafar,2 Salah A Aljarallah,3 Muqbil Saad Alqahtani,4 Fahad Abdullah Alamri,5 Awad O Aljohani,6 Majed D Alanazi,7 Turky J Arbaein,8 Amal M Zaidan,9 Mohammed Aljuaid,10 Krzysztof Goniewicz11 1Department of Emergency Medical Services, Prince Sultan bin Abdulaziz College for Emergency Medical Services, King Saud University, Riyadh, 11541, Saudi Arabia; 2SEHA Virtual Hospital, Ministry of Health, Riyadh, 1154, Saudi Arabia; 3Department of Family Medicine, King Khaled University Hospital, King Saud University, Riyadh, Saudi Arabia; 4Department of Dentistry, College of Dentistry, King Faisal University, Alhafouf, 36932, Saudi Arabia; 5Ambulatory Care Administration, Ministry of Health, Riyadh, 11525, Saudi Arabia; 6Fresenius Kabi Scientific Office Alsaif Building, Riyadh, 1141, Saudi Arabia; 7Department of Family Medicine, General Directorate of Health Affairs in Riyadh Region, Ministry of Health, Riyadh, 12822, Saudi Arabia; 8Department of Health Administration and Hospitals, College of Public Health and Health Informatics, Umm Al-Qura University, Makkah, Saudi Arabia; 9College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia, King Abdullah International Medical Research Center’s (KAIMRC), Riyadh, Saudi Arabia; 10Department of Health Administration, College of Business Administration, King Saud University, Riyadh, Saudi Arabia; 11Department of Security, Polish Air Force University, Deblin, PolandCorrespondence: Ahmed M Al-Wathinani, Email ahmalotaibi@ksu.edu.saIntroduction: This cross-sectional descriptive study evaluates the experiences and perceptions of healthcare providers (HCPs) regarding the 937 medical call center in Saudi Arabia, a key telemedicine initiative.Aim: To assess HCP satisfaction, identify challenges, and provide recommendations for improvement.Methods: Conducted from November 20th to December 15th, 2022, the study surveyed 454 HCPs, achieving a 90.5% response rate.Results: A majority (86.8%) of respondents were satisfied with the call center, valuing its ease of use and effectiveness in healthcare delivery. However, challenges such as the accuracy of remote medical assessments, the need for clearer telehealth regulations, and concerns over management support and consultation overlaps were identified. The study also highlights the importance of ongoing support and updates, comprehensive telehealth regulations, integration of more medical specialties, and improvements in system integration and data confidentiality.Conclusion: The study underscores the need for strategic enhancements to the 937 call center to further improve healthcare accessibility and efficiency in Saudi Arabia. These enhancements are vital for aligning telehealth services with Saudi Arabia’s healthcare objectives under Saudi Vision 2030.Keywords: telemedicine, Saudi Arabia, health care providers, patient satisfaction, health services accessibility, telehealth, medical informatics, health policy

Introduction: The emergence of high-efficacy disease-modifying therapies (HE DMT) for multiple sclerosis (MS) may pose challenges to the administration and monitoring burden of the therapies. This article presents the results of the Delphi consensus method to generate insights from experts on the administration and monitoring burden of HE DMT in Saudi Arabia with a special focus on cladribine., Methods: Between January and March 2023, a two-round modified Delphi method was used to establish consensus regarding the administration and monitoring burden of HE DMTs used for MS. Through a questionnaire, the advisors evaluated 17 properties of six individual HE DMTs on the basis of their clinical experience. Advisors were required to rank each property on a scale of 1-5, with 1 being the lowest burden and 5 being the highest burden., Results: Experts ranked cladribine as having the lowest monitoring burden, followed by ofatumumab and ocrelizumab. Natalizumab and fingolimod were ranked fourth, and alemtuzumab had the highest burden. During the first round, experts agreed on the scores of the administration burden properties, except for hospital visit time and facility use during administration for ofatumumab, route of administration for fingolimod, monitoring of specific side effects and frequency of lab tests at follow-up, and the washout period for natalizumab. During the second round, there was agreement on all properties., Conclusion: In the absence of alternative scientific data, recommendations from experts and their consensus provide useful insights into the administration and monitoring burden of HE DMTs used for MS in Saudi Arabia., Competing Interests: Declarations. Conflict of Interest: Seraj Makkawi received an honorarium for attending the advisory board meeting on which this article is based. Also, he reports personal fees from Roche, Merck, Novartis, Sanofi Genzyme, Biogen, Janssen, Biologix, AstraZeneca, and Horizon Therapeutics outside the submitted work. Salman Aljarallah received an honorarium for attending the advisory board meeting on which this article is based. Also, he reports receiving speaker and consultation fees from Roche, Merck, Novartis, Sanofi Genzyme, Biogen, Janssen, Biologix, AstraZeneca, and Horizon Therapeutics outside the submitted work. All authors participated in the closed meeting that gave rise to this article, which was organized and supported by Merck Serono Middle East FZ-Ltd. Ethical Approval: The study did not involve human participants, human data, or human material; thus, ethics committee approval was not required. The panelists were all authors of this paper., (© 2025. The Author(s).)

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct demyelinating diseases of the central nervous system, each characterized by unique patterns of motor, sensory, and visual dysfunction. While MS typically affects the brain and spinal cord, NMOSD predominantly targets the optic nerves and spinal cord. This study aims to elucidate the morphometric differences between MS and NMOSD by focusing on gray matter volume changes in specific brain regions. We also examined if temporal changes in follow-up MRI differentiate the two disorders. We analyzed anatomical T1-weighted MRI scans from 24 patients with NMOSD and 25 patients with MS using the CAT12 toolbox. Our analysis revealed significant differences in gray matter structure between the two patient groups. Notably, the thalamus was found to be consistently smaller in patients with MS compared to those with NMOSD. This finding aligns with previous research highlighting thalamic atrophy as a hallmark of MS and further underscores the thalamus's role in the disease's pathology. These results provide valuable insights into the distinct neuroanatomical features of MS and NMOSD, contributing to a better understanding of the mechanisms underlying these diseases. The study also emphasizes the importance of advanced imaging techniques in differentiating between MS and NMOSD, which may have implications for diagnosis and treatment strategies., 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 © 2025 Alosaimi, Alkanhal, Aldeligan, Alkhawajah, Albishi, Hilabi and Aljarallah.)

Purpose: The Multiple Sclerosis Impact Scale-29 (MSIS-29) is a patient self-reported outcome (PRO) that measures patients' quality of life, and it is divided into two sub-scales for the physical (PHYS) and psychological (PSYCH) domains. This study aimed to translate the MSIS-29 into Arabic, cross-culturally adapt it, and examine its psychometric properties., Materials and Methods: One hundred fifty patients with MS completed the MSIS-29-Ar, the Functional Assessment of Multiple Sclerosis (FAMS), and the Short-Form Health Survey (SF-36). After one week, 60 participants were asked to complete the MSIS-29-Ar again to examine test-retest reliability., Results: The MSIS-29-Ar was clear and understandable among patients with MS in Saudi Arabia. The internal consistency for the MSIS-29-Ar-PHYS was excellent, with a Cronbach's alpha of 0.955, and was good for the MSIS-29-Ar-PSYCH, with a Cronbach's alpha of 0.891. The test-retest reliability for MSIS-29-Ar-PHYS was ICC 2,1 = 0.97; 95% confidence interval (0.93, 0.99) and ICC 2,1 = 0.95.; 95% confidence interval (0.897, 0.976) for MSIS-29-Ar-PSYCH domains. The minimal detectable change with 95% confidence (MDC 95 ) was 10.28 and 13.37 for the MSIS-29-Ar-PHYS and MSIS-29-Ar-PSYCH, respectively. No floor and ceiling effects were observed. Convergent and divergent validity was supported by 75% of the predefined hypotheses and correlated with the other health-related quality-of-life measures, SF-36 and FAMS., Conclusion: The MSIS-29-Ar questionnaire is a valid and reliable outcome measure among Saudi patients with MS.IMPLICATION FOR REHABILITATIONRehabilitation specialists can confidently interpret patient scores in the MSIS-29-Ar to measure physical and psychological factors impacting patients' quality of life with Multiple Sclerosis (MS).Patients with unchanged clinical status will have similar scores in the MSIS-29-Ar with repeated scale administrations over time.The MSIS-29-Ar can be used in clinical practice and research studies to measure factors that impact the quality of life in Arabic-speaking patients with MS.

Background/objectives: Cognitive flexibility is the mental skill that allows a person to shift between different ideas or concepts and think about several concepts simultaneously. A commonly used tool to assess cognitive flexibility is the Cognitive Flexibility Scale (CFS). This study focused on translating and validating the CFS into Arabic, given the lack of existing Arabic tools for assessing cognitive flexibility. Methods: Conducted at King Saud University, Riyadh, between April and June 2024, the study employed random sampling and involved 529 participants, including 419 students and 110 patients. Results: The average participant age was 25.8 years, with females making up 56.9% of the sample. Participants completed the Arabic CFS, along with the Emotion Regulation Questionnaire (ERQ) and the Perceived Stress Scale (PSS), at two time points 3-6 weeks apart. Reliability was evaluated through internal consistency (Cronbach's alpha = 0.8) and test-retest reliability (intraclass correlation coefficient = 0.82). Item analysis indicated that removing any single item did not significantly impact overall reliability, and inter-item correlations were strongest between items 4 and 6 (0.55) and items 6 and 7 (0.51). Validity was assessed through face, content, and construct validity, with factor analysis revealing a dominant single component accounting for 34.4% of the variance, confirming the scale's unidimensionality. Content validity indices for all items exceeded 0.9 in terms of relevance, importance, simplicity, and clarity. The Arabic CFS demonstrated good construct validity, showing significant correlations with the ERQ's reappraisal and suppression dimensions and the PSS. Conclusion: In conclusion, the Arabic version of the CFS is a valid and reliable tool for assessing cognitive flexibility in Arabic-speaking populations. This tool will be valuable in both clinical and research settings within Saudi Arabia, offering a robust instrument for evaluating cognitive flexibility.

Objective: To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future disability., Background: There is a need to better understand the full spectrum of clinical and paraclinical features and long-term impact of SPSD., Design/methods: Observational study from 1997 to 2022 at Johns Hopkins. Clinical phenotypes included classic SPS, partial SPS (limb or trunk limited), SPS-plus (classic features plus cerebellar/brainstem involvement), and progressive encephalomyelitis with rigidity and myoclonus (PERM). Outcome measures were modified Rankin scale (mRS) and use of assistive device for ambulation. Multivariate logistic regression was used to assess significant predictors of outcomes., Results: Cohort included 227 individuals with SPSD with mean follow-up of 10 years; 154 classic, 48 SPS-plus, 16 PERM, and 9 partial. Mean age at symptom onset was 42.9 ± 14.1 years, majority were white (69.2%) and female (75.8%). Median time to diagnosis was 36.2 months (longest for SPS-plus and PERM) and 61.2% were initially misdiagnosed. Most had systemic co-morbidities and required assistive devices for ambulation. Female sex (OR 2.08; CI 1.06-4.11) and initial brainstem/cerebellar involvement (OR 4.41; CI 1.63-14.33) predicted worse outcome by mRS. Older age at symptom onset (OR 1.04; CI 1.01-1.06), female sex (OR 1.99; CI 1.01-4.01), Black race (OR 4.14; CI 1.79-10.63), and initial brainstem/cerebellar involvement (OR 2.44; CI 1.04-7.19) predicted worse outcome by use of assistive device. Early implementation of immunotherapy was associated with better outcomes by either mRS (OR 0.45; CI 0.22-0.92) or use of assistive device (OR 0.79; CI 0.66-0.94)., Conclusions: We present the expanding phenotypic variability of this rare spectrum of disorders and highlight potential predictors of future disability., (© 2023. The Author(s).)

The Expanded Disability Status Scale (EDSS) is commonly used to measure and quantify disabilities in patients with multiple sclerosis (MS). The patient-determined disease steps (PDDS) scale is a patient-reported measure of disability that is useful in MS. However, the Arabic version of the PDDS has only been tested in Jordanian patients. Although both populations share similar Arabic languages, it is plausible that differences in dialects and educational systems could alter the generalizability of the tool. In this prospective study, patients with MS were asked to complete a printed translated version of the (PDDS), and the results were compared to their EDSS scores, functional system scores, and walking speed measures. Patients with relapsing or progressive MS were included in the study. Spearman rho rank-order correlation coefficients (P) were used to measure the correlation between the PDDS and other variables. We considered previously reported P values > .1, .3, and .5 as small, moderate, and strong correlations, respectively. A total of 79 patients completed the study. The PDDS showed a strong correlation with the EDSS (P = .69, 95% confidence interval 0.55-0.79, P < .001). PDDS is associated with cerebellar, pyramidal, and bladder dysfunctions. It was also moderately correlated with the timed-25-foot walk test and timed-up-and-go test. The Arabic version of the PDDS performed similarly to English and other languages when tested on a cohort of patients with MS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To investigate the frequency, clinical findings and outcomes of occlusive retinal vasculitis in patients with multiple sclerosis (MS)., Methods: A retrospective case series., Results: During the period between January 2000 and December 2021, we identified 24 patients who were diagnosed to have uveitis associated with MS. Among them, four (16.6%) patients presented with bilateral occlusive retinal vasculitis who were diagnosed to have MS prior to presentation. All patients were treated successfully with a combination of systemic corticosteroids combined with mycophenolate mofetil. In addition, scatter laser photocoagulation was applied to the ischemic retina in all eyes., Conclusions: Early recognition and prompt treatment with systemic immunosuppressive agents and scatter laser photocoagulation prevent complications and improve outcomes in MS patients with occlusive retinal vasculitis.

Objectives: This study assessed the prevalence of restless leg syndrome (RLS) among patients with multiple sclerosis (pwMS) and the association between RLS and MS disease duration, sleep disturbance, and daytime fatigue., Methods: In this cross-sectional study, we interviewed 123 patients via phone calls using preset questionnaires containing the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria, Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) diagnostic criteria validated in both Arabic and English. The prevalence of RLS in MS was compared to a group of healthy controls., Results: The prevalence of RLS in pwMS, defined by meeting all four requirements included in the IRLSSG diagnostic criteria, was 30.3% compared to 8.3% in the control group. About 27.3% had mild RLS, 36.4% presented with moderate, and the remaining had severe or very severe symptoms. Patients with MS who experience RLS had a 2.8 times higher risk of fatigue compared to pwMS without RLS. pwMS with RLS had worse sleep quality, with a mean difference of 0.64 in the global PSQI score. Sleep disturbance and latency had the most significant impact on sleep quality., Conclusion: The prevalence of RLS among MS patients was significantly higher compared to the control group. We recommend educating neurologists and general physicians to increase their awareness of the increasing prevalence of RLS and its association with fatigue and sleep disturbance in patients with MS., 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 Aljarallah, Alkhawajah, Aldosari, Alhuqbani, Alqifari, Alkhuwaitir, Aldawood, Alshenawy and BaHammam.)

Introduction: The advent of new disease-modifying therapies (DMTs), such as monoclonal antibodies (mAbs), resulted in significant changes in the treatment guidelines for Multiple sclerosis (MS) and improvement in the clinical outcomes. However, mAbs, such as rituximab, natalizumab, and ocrelizumab, are expensive with variable effectiveness rates. Thus, the present study aimed to compare the direct medical cost and consequences (e.g., clinical relapse, disability progression, and new MRI lesions) between rituximab and natalizumab in managing relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia. Also, the study aimed to explore the cost and consequence of ocrelizumab in managing RRMS as a second-choice treatment., Methods: The electronic medical records (EMRs) of patients with RRMS were retrospectively reviewed to retrieve the patients' baseline characteristics and disease progression from two tertiary care centers in Riyadh, Saudi Arabia. Biologic-naïve patients treated with rituximab or natalizumab or those switched to ocrelizumab and treated for at least six months were included in the study. The effectiveness rate was defined as no evidence of disease activity (NEDA-3) (i.e., absence of new T2 or T1 gadolinium (Gd) lesions as demonstrated by the Magnetic Resonance Imaging (MRI), disability progression, and clinical relapses), while the direct medical costs were estimated based on the utilization of healthcare resources. In addition, bootstrapping with 10,000 replications and inverse probability weighting based on propensity score were conducted., Results: Ninety-three patients met the inclusion criteria and were included in the analysis (natalizumab (n = 50), rituximab (n = 26), ocrelizumab (n = 17)). Most of the patients were otherwise healthy (81.72%), under 35 years of age (76.34%), females (61.29%), and on the same mAb for more than one year (83.87%). The mean effectiveness rates for natalizumab, rituximab, and ocrelizumab were 72.00%, 76.92%, and 58.83%, respectively. Natalizumab mean incremental cost compared to rituximab was $35,383 (95% CI: $25,401.09- $49,717.92), and its mean effectiveness rate was 4.92% lower than rituximab (95% CI: -30-27.5) with 59.41% confidence level that rituximab will be dominant., Conclusions: Rituximab seems to be more effective and is less costly than natalizumab in the management of RRMS. Ocrelizumab does not seem to slow the rates of disease progression among patients previously treated with natalizumab., (© 2023. The Author(s).)

Treatment-pattern data suggest that some patients with multiple sclerosis (MS) in the Kingdom of Saudi Arabia (KSA) may not be receiving optimal treatment. A virtual meeting of ten expert Saudi neurologists, held on October 23, 2020, discussed unmet needs in relapsing-remitting MS (RRMS), and the role of ofatumumab as a suitable treatment in the KSA. Multiple unmet needs were identified: poor quality of life, with high rates of depression and anxiety; a negative impact of MS on work ability; treatment choices that may compromise efficacy for safety or vice versa; inconvenient or complex dosage regimens; and limited access to patient education and support. Early use of highly effective disease-modifying treatments (DMTs) results in better patient outcomes than starting with less effective treatments and downstream escalation, but this strategy may be underutilized in the KSA. B cells are important in MS pathogenesis, and treatments targeting these may improve clinical outcomes. Ofatumumab differs from other B cell-depleting therapies, being a fully human monoclonal antibody that binds to CD20 at a completely separate site from the epitope bound by ocrelizumab, and being administered by subcutaneous injection. When compared with teriflunomide in two randomized, phase 3 clinical trials in patients with RRMS, ofatumumab was associated with significant reductions in annualized relapse rates, rates of confirmed disability worsening, and active lesions on magnetic resonance imaging. The incidence of adverse events, including serious infections, was similar with the two treatments. Ofatumumab is a valuable first- or second-line treatment option for RRMS in the KSA, particularly for patients who would benefit from highly effective DMTs early in the disease course, and for those who prefer the convenience of self-injection. Future research will clarify the position of ofatumumab in RRMS treatment, and comparative cost data may support the broad inclusion of ofatumumab in formularies across the KSA., (© 2022. The Author(s).)

Introduction: Over the past twenty years, dental practice in Saudi Arabia has developed considerably, along with increase in population's knowledge of their rights. However, there is a lack of evidence and research on dental malpractice lawsuit cases in Saudi Arabia. The aim of this study was to assess the prevalence and content of legal suits regarding dental malpractice in Saudi Arabia, and to explore the factors and circumstances that were associated with these cases., Methods: This was a retrospective study on dental malpractice litigation cases between January 2017 and December 2020. Only cases with final court verdicts were included. The cases were collected from 13 Medico-Legal Committee (MLC) across Saudi Arabia while practitioners' data were retrieved from the General Directorate of Healthcare Licensing at Ministry of Health (MOH). A designed data sheet was used, which was categorized into three main sections: plaintiff demographic data, defendant demographic, data case details in the court., Results: During the four years period, 864 cases with verdicts were studied. Most of the cases were against general dental practitioners, and majority of complaints involved prosthodontic procedures followed by endodontics. The majority of the malpractice lawsuit cases (93 %) were against non-Saudi dental practitioners and 72 % were against experienced practitioners with more than ten years of experience. Almost all cases were in the private sector. Only 10 % of cases had a consent form previously provided to the patients before treatment, and most of cases lacked proper medical documentation. The mean average trial period was 3.3 months and 76 % of defendants were found guilty., Conclusion: The number of cases is rising since 2017. Good documentation, compliance to informed consent protocols and dental privileges helped practitioners to avoid being found guilty., Competing Interests: 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., (© 2022 The Authors.)

Background: Multiple sclerosis (MS) is an inflammatory disease associated with adverse effects: including depression, anxiety, fatigue, which may affect physical activity and the quality of life (QoL) among patients with MS (pwMS)., Objective: This study aims to assess the prevalence of depression, anxiety, and fatigue among pwMS who have no physical disability in Saudi Arabia, and demonstrate any correlation between these factors and physical activity as well as the QoL., Methods: A cross-sectional study was conducted in the Neuroimmunology outpatient clinics in King Fahad Medical City (KFMC) and King Saud University Medical City (KSUMC) in Riyadh City, KSA. The Arabic version of the Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression levels. The HADS scores were then categorized into three levels according to the total points: normal (0-7 points), borderline (7-10 points), and anxiety/depression (11 - 21 points). The Arabic version of the Fatigue Severity Scale (FSS) was used to measure fatigue (cut-off point ≥5). The physical activity was measured by the Arabic version of the short form of the International Physical Activity Questionnaire (IPAQ), which measure time spent walking, moderate- and vigorous-intensity physical activity of at least 10 minutes duration. The QoL was also measured by the Arabic version of the EuroQOL five-dimensional (EQ-5D-3L) instrument (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression)., Results: A total of 323 pwMS participated in this study, 83 had scores that indicated anxiety (25.7%) and 44 had depression (13.6%). The majority of patients had scores with the normal range of depression and anxiety (70% and 57% respectively). The mean of EuroQol Group visual analogue scale (EQ-VAS) score was 80.43 (SD=19.8). 156 (48.3%) out of 323 pwMS reported fatigue while the remainder had no fatigue (n=167, 51.7%). The results indicate that only 143 patients (44.3%) had participated in vigorous physical activity during the last 70 days, with a median of 3 days per week (IQR= 5-3) and a median of 60 minutes per day 0 (Interquartile range: IQR = 60-30). Only 149 patients (49.2%) had patricpated in moderate physical activities during the previous week with a median of 3 days per week (IQR = 5-3) and a median of 40 minutes per day (IQR = 60-30). 194 patients had participated in walking activities (60.0%) with a median of 5 days per week (IQR = 7-3) and a median of 45 minutes per day (IQR = 60-30). The results revealed that fatigue was positively correlated with depression (r = 0.407, p-value < 0.001) and anxiety (r = 0.289, p-value < 0.001)., Conclusion: The current study shows depression, anxiety, and fatigue tend to be correlated and clustered together among pwMS in our cohort. However, fatigue is not associated with the intensity of physical activity undertaken. The results of this study are important for the improvement of the clinical management of MS patients., 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 © 2022 AlSaeed, Aljouee, Alkhawajah, Alarieh, AlGarni, Aljarallah, Ayyash and Abu-Shaheen.)

Background: Multiple sclerosis (MS) is an inflammatory chronic disease that is characterized by an increased prevalence of adverse mental health outcomes in patients with MS (pwMS). The main aim of this study is to investigate the factors of depression and anxiety in pwMS in the Kingdom of Saudi Arabia (KSA)., Materials and Methods: This is a cross-sectional study conducted in KSA during the period from March to June 2020. Participants were recruited from the Neuroimmunology clinics in King Fahad Medical City (KFMC) and King Saud University medical city (KSUMC)in Riyadh City, KSA. The Hospital Anxiety and Depression Scale (HADS) was used to measure depression and anxiety. Fatigue Severity Scale (FSS) was used to measure fatigue in pwMS. A simple random sampling technique was utilized to select participants and the data were analyzed using SPSS v.24.0., Results: A total of 529 participants participated in this study with a response rate of 53.1%. The prevalences of anxiety and depression were 35.3% and 19.7%, respectively. The findings also revealed that depression was more likely to be significantly affected by being male, low education, unemployment, physical inactivity, and fatigue but the anxiety was significantly affected by region, unemployment, short duration since last MS relapse, physical inactivity, and fatigue., Conclusion: Anxiety and depression are not uncommon in pwMS. Given their impact on the lives of affected patients, early detection and management of these symptoms and their associated factors are crucial., (© 2022. The Author(s).)

Background: The prevalence of multiple sclerosis (MS) is increasing in Gulf Cooperation Council (GCC) countries. Multiple sclerosis contributes to significant burden on patients and caregivers. The pharmacological treatment in MS involves treating acute exacerbations and preventing relapses and disability progression using disease-modifying therapies. Clinical evidence suggests that teriflunomide is one of the therapeutic choices for patients with relapsing-remitting MS (RRMS). However, genetic and cultural differences across different regions may contribute to variations in drug use. Therefore, it is necessary to consider real-world evidence for teriflunomide usage in GCC countries., Methods: An expert group for MS gathered from GCC countries in December 2020. The consensus highlighting role of teriflunomide in MS management has been developed using clinical experiences and evidence-based approach., Results: The expert-recommended patient profile for teriflunomide usage includes individuals aged 18 years and above, both men and women (on effective contraceptives) with clinically isolated syndrome or RRMS. The factors considered were cost-effectiveness of the drug, patient preference, adherence, monitoring, established safety profile, and coronavirus disease 2019 status., Conclusion: Expert recommendations based on their clinical experience will be more helpful to clinicians in clinical settings regarding the usage of teriflunomide and provide valuable insights applicable in day-to-day practice., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Introduction: There are a number of well-established risk factors for multiple sclerosis (MS). Other factors, however, showed conflicting or inconsistent results. Here, we examine some factors that are unique to or more practiced in Saudi Arabia (SA) and the Arab region such as waterpipe tobacco smoking (WTS), face veiling, raw milk (RM) and camel milk (CM) consumption, and tuberculosis (TB) infection in addition to other traditional factors., Methods: This is a sex- and age-matched case-control study in which we used a structured questionnaire to examine the relation between a number of factors and exposures and the risk of MS. Three hundred MS patients and 601 controls were included. Data were analyzed across different statistical models using logistic regression adjusting for age, sex, marital status, duration of breastfeeding, age first joining school, coffee consumption, and face exposure., Results: Cigarette smoking (OR = 1.79, [95% CI: 1.01-3.17], p = 0.047), WTS (OR = 2.25, [95% CI: 1.21-4.15], p = 0.010), and CM consumption (OR = 2.50, [95% CI: 1.20-5.21], p = 0.014) increased the risk of MS, while performing hajj (OR = 0.47, [95% CI: 0.34-0.67], p = 0.001), TB infection (OR = 0.29, [95% CI: 0.11-0.78], p = 0.015), face veiling (OR = 0.32, [95% CI: 0.23-0.47], p = 0.001), and coffee consumption (OR = 0.67, [95% CI: 0.49-0.89], p = 0.008) appeared to be associated with decreased risk. No association was found between fast food, processed meat, soft drinks, animal milk (other than camel), or RM consumption and the risk of MS., Conclusion: The results of this case-control study confirm that different means of tobacco smoking are associated with increased risk of MS. It also sheds more light on the complex association between infections and MS., (© 2021 S. Karger AG, Basel.)

The very fact that multiple sclerosis (MS) is incurable and necessitates life-long care makes it one of the most burdensome illnesses. The aim of this study was to compare the cost-effectiveness of orally administered medications (e.g., fingolimod, dimethyl fumarate, and teriflunomide), interferon (IFN)-based therapy, and monoclonal antibodies (MABs) (e.g., natalizumab and rituximab) in the management of relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia using real-world data. This was a retrospective cohort study in which patients with RRMS aged ≥18 years without any other chronic health conditions with non-missing data for at least 12 months were recruited from the electronic health records of a university-affiliated tertiary care center. Multiple logistic regressions controlling for age, sex, and duration of therapy were conducted to examine the odds of disability progression, clinical relapse, MRI lesions, and composite outcome (e.g., relapse, lesion development on MRI, disability progression). The number of patients who met the inclusion criteria and were included in the analysis was 146. Most of the patients were female (70.51%) and young (e.g., ≤35 years of age). There were 40 patients on the orally administered agents (e.g., dimethyl fumarate, teriflunomide, fingolimod), 66 patients were on IFN-based therapy (e.g., Rebif ® ), and 40 patients were on monoclonal antibodies (e.g., rituximab and natalizumab). Patients on MABs had lower odds of the composite outcome (OR = 0.17 (95% CI: 0.068-0.428)). The use of orally administered agents was dominant (e.g., more effective and less costly), with average annual cost savings of USD -4336.65 (95% CI: -5207.89--3903.32) and 8.11% higher rate of effectiveness (95% CI: -14.81-18.07) when compared with Rebif ® . With regard to the use of MABs in comparison to Rebif ® , MABs were associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 1381.54 (95% CI: 421.31-3621.06) and 43.11% higher rate of effectiveness (95% CI: 30.38-61.15) when compared with Rebif ® . In addition, the use of MABs was associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 5717.88 (95% CI: 4970.75-8272.66) and 35% higher rate of effectiveness (95% CI: 10.0-42.50) when compared with orally administered agents. The use of MABs in the management of RRMS among the young patient population has shown to be the most effective therapy in comparison to both IFN-based therapy (e.g., Rebif ® ) and orally administered agents, but with higher cost. Orally administered agents resulted in better outcomes and lower costs in comparison to IFN-based therapy. Future studies should further examine the cost-effectiveness of different disease-modifying therapies for the management of RRMS using more robust study designs.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread and developed as a pandemic threatening global health. Patients with multiple sclerosis (MS)-an autoimmune demyelinating inflammatory disease of the central nervous system (CNS)-are predominantly treated with immunomodulatory/immunosuppressive disease-modifying therapies (DMTs), which can increase the risk of infection. Therefore, there is concern that these patients may have a higher risk of COVID-19. In response to growing concerns of neurologists and patients, this study aimed to determine the prevalence, severity, and possible complications of COVID-19 infection in patients with MS in Saudi Arabia (SA)., Methods: In this prospective cohort study, demographic and clinical data were obtained from patients residing in SA with MS who had a positive result for COVID-19 per reverse transcription-polymerase chain reaction test or viral gene sequencing, using respiratory or plasma samples. Comparison of COVID-19 severity groups was performed using one-way ANOVA or Kruskal-Wallis test for numerical variables and Chi-squared test for categorical variables., Results: Seventy patients with MS and COVID-19 (71% female) were included in this analysis. Of the 53 (75.7%) patients receiving a DMT at the time of COVID-19 infection, the most frequently used DMTs were fingolimod (25%) and interferon-beta (25%). Nine (13%) patients had MS relapse and were treated with intravenous methylprednisolone in the four weeks before COVID-19 infection. The most common symptoms at the peak of COVID-19 infection were fever (46%), fatigue (37%), and headache (36%). Symptoms lasted for a mean duration of 8.7 days; all symptomatic patients recovered and no deaths were reported. COVID-19 severity was categorized in three groups: asymptomatic (n = 12), mild-not requiring hospitalization (n = 48), and requiring hospitalization (n = 10; two of whom were admitted to the intensive care unit [ICU]). Between the three groups, comparison of age, body mass index , Expanded Disability Severity Score , MS disease duration, and DMT use at the time of infection showed no significant differences. A higher percentage of patients who were admitted to hospital or the ICU (40%; p = 0.026) presented with an MS relapse within the prior four weeks compared with those who were asymptomatic or had a mild infection (both 8.3%)., Conclusion: These findings present a reassuring picture regarding COVID-19 infection in patients with MS. However, patients with MS who have had a relapse in the preceding four weeks (requiring glucocorticoid treatment) may have an increased risk of severe COVID-19., (Copyright © 2021. Published by Elsevier B.V.)

Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease. Etiology is thought to be multifactorial with genetic and environmental factors interplay. Our objective in this study is to evaluate culture specific and other early life risk factors for MS. We examined the association between MS and breastfeeding including shared breastfeeding, parental consanguinity, being born abroad or living abroad during childhood, prematurity, vaccination, tonsillectomy, rank among siblings, number of siblings, number of household members (HHM) at birth, and age first time joining school., Methods: This is an age and sex matched case-control study that was conducted in Riyadh, Kingdom of Saudi Arabia (KSA). We enrolled 300 cases and 601 controls. A structured questionnaire about demographics, consanguinity and potential environmental factors was answered by participants. Data was analyzed using logistic regression adjusting for covariates occurring later in life such as waterpipe smoking and performing Hajj., Results: About two thirds of the cases and the controls were females. Mean age was 34.8 (9.2) for the cases and 33.6 (10.6) for the controls. We found that shared breastfeeding (OR=0.58; 95% CI, 0.35-0.96, p = 0.033), and older age first joining school (OR=0.83; 95% CI, 0.73-0.94, p = 0.005) were associated with decrease risk of MS. While longer duration of breastfeeding by biological mother (OR=1.03; 95% CI, 1.01-1.04, p = 0.001), rank among siblings of ≥6 (OR=1.69; 95% CI, 1.11-2.56, p = 0.014), and larger number of HHM at birth (OR=2.32; 95% CI, 1.64-3.28, p = 0.001) were associated with increased risk. Patients with MS were less likely to receive formula with breastfeeding than controls (OR=0.72; 95% CI, 0.51-0.99, p = 0.046). No association was found with breastfeeding by biological mother, number of siblings, prematurity, being born abroad or living abroad during childhood, vaccination, consanguinity, or tonsillectomy., Conclusion: The findings of this case-control study add to the accumulating evidence that early life factors could modify the risk of developing MS. Among these, novel associations with shared breastfeeding and number of HHM at birth are suggested. Future studies are needed to verify the observed results., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Intravenous immunoglobulin (IVIG) has been shown to be effective for the treatment of stiff person syndrome (SPS). However, some patients might not tolerate it. We report the tolerability profile of subcutaneous immunoglobulin (SCIg) in patients with SPS who did not tolerate IVIG. To our knowledge, the use of SCIg in SPS has not been reported before in a case series., Patient Concerns: The five patients included in this case series presented with various combinations of symptoms of spasms, axial and limb stiffness, and exaggerated responses to outside stimuli. These symptoms often lead to gait and functional impairment., Diagnosis: Patients were diagnosed with classic SPS as they met the clinical criteria, which require the presence of spasms, axial rigidity, and hyperexcitability., Interventions: Subcutaneous immunoglobulin infusion., Outcomes: Five patients were identified that were treated with SCIg. Three tested positive for serum anti-glutamic acid decarboxylase 65 antibodies prior to any treatment. The mean age at SCIg initiation was 33 years (range: 22-47). The mean duration of SPS prior to SCIg initiation was 5.9 years (range: 2.5-7). All patients used IVIG for at least two months (up to 18 months) but switched to SCIg due to IVIG side effects. Duration of SCIg use ranged from 4 months to 6 years (mean, 19.2 months). Upon switching to SCIg, the SPS symptoms remained stable. SCIg was well-tolerated in most as only one patient discontinued SCIg due to side effects., Conclusion: This case series highlights that SCIg could be a treatment option for patients with SPS, especially when IVIG is not feasible. Injection site reactions might be a limiting factor in some patients treated with SCIg. Prospective controlled studies are needed to confirm SCIg treatment durability and efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue., Methods: In this randomised, placebo-controlled, four-sequence, four-period, crossover, double-blind trial, patients with multiple sclerosis who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic multiple sclerosis centres in the USA. Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to 100 mg twice daily), methylphenidate (up to 10 mg twice daily), or placebo, each given for up to 6 weeks. All patients were intended to receive all four study medications, in turn, in one of four different sequences with 2-week washout periods between medications. A biostatistician prepared a concealed allocation schedule, stratified by site, randomly assigning a sequence of medications in approximately a 1:1:1:1 ratio, in blocks of eight, to a consecutive series of numbers. The statistician and pharmacists had no role in assessing the participants or collecting data, and the participants, caregivers, and assessors were masked to allocation. The primary outcome measure was the MFIS measured while taking the highest tolerated dose at week 5 of each medication period, analysed by use of a linear mixed-effect regression model. This trial is registered with ClinicalTrials.gov, NCT03185065 and is closed., Findings: Between Oct 4, 2017, and Feb 27, 2019, of 169 patients screened, 141 patients were enrolled and randomly assigned to one of four medication administration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequence; 34 (24%) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 37 (26%) patients to the methylphenidate, modafinil, placebo, and amantadine sequence. Data from 136 participants were available for the intention-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51·3 (95% CI 49·0-53·6) at baseline, 40·6 (38·2-43·1) with placebo, 41·3 (38·8-43·7) with amantadine, 39·0 (36·6-41·4) with modafinil, and 38·6 (36·2-41·0) with methylphenidate (p=0·20 for the overall medication effect in the linear mixed-effect regression model). As compared with placebo (38 [31%] of 124 patients), higher proportions of participants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40%] of 125 patients), and methylphenidate (51 [40%] of 129 patients). Three serious adverse events occurred during the study (pulmonary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requiring hospital admission while taking modafinil)., Interpretation: Amantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis., Funding: Patient-Centered Outcomes Research Institute., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cobalamin (vitamin B 12 ) deficiency often manifests with neurologic symptoms and may rarely mimic multiple sclerosis (MS) among other neurological disorders. However, MRI changes associated with cobalamin deficiency are typically spinal predominant and distinct from MS-related changes. We report a case of a patient with cobalamin deficiency who was recommended by her primary neurologist to commence treatment with ocrelizumab, a potent anti-CD20 B-cell depleting monoclonal antibody, after being diagnosed with primary progressive MS. However, cervical spine MRI demonstrated changes classical of cobalamin deficiency including 'inverted V sign' signal hyperintensity and following parenteral cobalamin supplementation her neurological symptoms quickly and dramatically improved., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To document functional differences between monocyte-derived macrophages (MDMs) of patients with MS and the ability of age/sex-matched healthy donor cells to phagocytose human myelin and to investigate the molecular mechanisms that underlie this., Methods: MDMs were derived from peripheral blood monocytes of 25 untreated patients with relapsing-remitting MS and secondary progressive MS and age/sex-matched healthy controls (HCs). Phagocytosis was assessed by flow cytometry using fluorescently labeled human myelin. Quantification of messenger RNA and protein expression of Tyro3, Axl, and MerTK family molecules was determined by quantitative PCR, Western blotting, and flow cytometry., Results: Cells of patients with MS display a reduced ability to phagocytose human myelin but not red blood cells as compared to matched HCs. These cells express significantly lower levels of the phagocytic tyrosine kinase receptor, MerTK, and its natural ligand, growth arrest-specific 6, independently of the activation state of the cells. Increased expression of interleukin 10 following myelin uptake by healthy donor cells is lost in MDMs of patients with MS; this effect is mediated through the MerTK pathway. Treatment of MS cells with transforming growth factor β (TGFβ) restored both phagocytosis and expression deficits., Conclusions: We describe a molecular mechanism that underlies a defect in myelin phagocytosis by macrophages generated from patients with MS. This abnormality involves decreased expression of MerTK and its ligands and can be rescued by treatment with TGFβ.

Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging mice following severe brain ischemia and that early anticonvulsive treatment may prevent seizure genesis and improve overall outcomes.

Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16-20 months-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6-8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Among the rare neurological complications of substances of abuse is the selective cerebral white matter injury (leukoencephalopathy). Of which, the syndrome of delayed post hypoxic encephalopathy (DPHL) that follows an acute drug overdose, in addition to "chasing the dragon" toxicity which results from chronic heroin vapor inhalation remain the most commonly described syndromes of toxic leukoencephalopathy. These syndromes are reported in association with opioid use. There are very few cases in the literature that described leukoencephalopathy following benzodiazepines, especially with an acute and progressive course. In this paper, we present a patient who developed an acute severe fatal leukoencephalopathy following hypoxic coma and systemic shock induced by benzodiazepine overdose., Case Presentation: A 19-year-old male was found comatose at home and brought to hospital in a deep coma, shock, hypoxia, and acidosis. Brain magnetic resonant imaging (MRI) revealed a strikingly selective white matter injury early in the course of the disease. The patient remained in a comatose state with no signs of neurologic recovery until he died few weeks later following an increase in the brain edema and herniation., Conclusion: Toxic leukoencephalopathy can occur acutely following an overdose of benzodiazepine and respiratory failure. This is unlike the usual cases of toxic leukoencephalopathy where there is a period of lucidity between the overdose and the development of white matter disease. Unfortunately, this syndrome remains of an unclear pathophysiology and with no successful treatment.