Overview of Structural and Functional Insights of SLFN12 Associated With Different Diseases.

Schlafen12 is a member of the Schlafen gene family where Slfns have been linked to many functions such as anti-proliferation and cell differentiation, viral replication inhibition, migration of cancer cells and invasion prevention, and sensitivity to DNA-damaging medicines. Researchers are interested in studying the biochemical mechanisms that control thymocyte development to extract and describe gene expression and transcriptionally elevated by the process of positive selection that led to the discovery of this novel gene family. This review aims to give adequate knowledge about human SLFN12 by reviewing the most notable papers from five reliable databases regarding SLFN12 milestones and alterations in SLFN12 expression in various disease discoveries from 1997 to the present. In conclusion, SLFN12 seems to be linked with autoimmune diseases such as multiple sclerosis. Furthermore, SLFN12 levels could modify the effects of radiation and chemotherapy.

Prospective Matched Case-Control Study of Over-Early P100 Wave Latency in Migraine with Aura.

A sizable portion of the world's population suffers from migraines with aura. The purpose of this research is to describe the findings of a case-control study that was carried out to gain a better understanding of how migraine with aura manifests. The research looked at the P100 delay of the visual-evoked potential in both eyes of 92 healthy people and 44 patients who suffered from migraines with visual aura. All of the participants in the study were recruited from King Fahad University Hospital in Saudi Arabia. Both sets of people had the same ancestry and originated from the same location. Patients who suffered from migraines with aura exhibited a significantly shorter P100 delay in both eyes compared to healthy controls (p = 0.001), which is evidence that their early visual processing was distinct. In order to arrive at these findings, we compared people who suffer from migraines with aura to people who do not suffer from migraines and used them as subjects. These findings contribute to the ongoing attempts to bring the disease under control and provide vitally significant new information regarding the functioning of headaches with auras. The primary focus of study in the future should be on determining the nature of the connection between issues with early visual processing and headaches with aura.

The important role of family members in guiding medical professions to reach a diagnosis: Case report of under-noticed bilateral apraxia of eyelid closure.

Apraxia of eyelid closure (AEC) is a rare disorder characterized by the inability to close the eyes on command with the preservation of the motor and sensory systems, coordination, comprehension, and cooperation. The prevalence of AEC is extremely small and the exact pathophysiological mechanisms underlying this condition remain unknown. It is, however, associated with extrapyramidal disorders. Very few cases of bilateral AEC have been reported. We report a case of an 81-year-old male patient having multiple comorbidities including neurological, respiratory, and abnormalities complicated by COVID-19 infection, who developed AEC that was noticed by the caregiver. We illustrate the clinical course leading to the diagnosis of bilateral AEC and highlight the important role of the caregiver in reporting subtle signs such as AEC.

Determinants of quality of life in patients with hemorrhagic stroke, Saudi Arabia: A cross-sectional study.

Background: Previous studies demonstrated that stroke had an inverse impact on patients' physical, mental, and social quality of life. Aim: To determine factors contributing to the health-related quality of life (HRQOL) of Saudi hemorrhagic stroke survivors. Methods: A cross-sectional study was done at King Abdulaziz University Hospital (KAUH), Jeddah, KSA, on adult stroke patients. Data about the patients' socio-demographic characters and clinical data were obtained. The Stroke-Specific QOL (SSQOL) scale was used to measure the HRQOL. Results: The mean Stroke-Specific QOL (SSQOL) domains sore was 163.8 ± 46.29. Male patients and those who had bilateral lesions had a significantly higher mean SSQOL score. A non-significant positive correlation was found between the SSQOL score and the patients' age and post-stroke duration. And a non-significant relationship was found between mean SSQOL score and patients' nationality, educational level, smoking, marital and financial status, income, social support, insurance or other clinical data, hemorrhagic type, surgical treatment and follow up, comorbidities, or the year and duration of diagnosis. Conclusion: There is a need to use stroke rehabilitation programs to improve physical and functional independence and take into account the influence of the side of lesion on HRQOL.

Saudi consensus recommendations on the management of multiple sclerosis: MS management in children and adolescents.

Multiple sclerosis (MS) most commonly presents in young adults, although 3-5% of patients develop MS prior to the age of 18 years. The new and comprehensive consensus for the management of MS in Saudi Arabia includes recommendations for the management of MS and other CNS inflammatory demyelinating disorders in pediatric and adolescent patients. This article summarizes the key recommendations for the diagnosis and management of these disorders in young patients. Pediatric and adult populations with MS differ in their presentation and clinical course. Careful differential diagnosis is important to exclude alternative diagnoses such as acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica spectrum disorders (NMOSD). The diagnosis of MS in a pediatric/adolescent patient is based on the 2017 McDonald diagnostic criteria, as in adults, once the possibility of ADEM or NMOSD has been ruled out. Few data are available from randomized trials to support the use of a specific disease-modifying therapy (DMT) in this population. Interferons and glatiramer acetate are preferred initial choices for DMTs based on observational evidence, with the requirement of a switch to a more effective DMT if breakthrough MS activity occurs.

Registry of patients with multiple sclerosis and COVID-19 infection in Saudi Arabia.

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.

Managing multiple sclerosis in the Covid19 era: a review of the literature and consensus report from a panel of experts in Saudi Arabia.

Disease-modifying therapies (DMT) for relapsing-remitting MS (RRMS) act on the immune system, suggesting a need for caution during the SARS-CoV2/Covid-19 pandemic. A group of experts in MS care from Saudi Arabia convened to consider the impact of Covid-19 on MS care in that country, and to develop consensus recommendations on the current application of DMT therapy. Covid-19 has led to disruption to the care of MS in Saudi Arabia as elsewhere. The Expert Panel considered a DMT's overall tolerability/safety profile to be the most important consideration on whether or not to prescribe at this time. Treatment can be started or continued with interferon beta, teriflunomide, dimethyl fumarate, or natalizumab, as these DMTs are not associated with increased risk of infection (there was no consensus on the initiation of other DMTs). A consensus also supported continuing treatment regimens with fingolimod (or siponimod) and cladribine tablets for a patient without active Covid-19. No DMT should be imitated in a patient with active Covid-19, and (only) interferon beta could be continued in the case of Covid-19 infection. Vaccination against Covid-19 is a therapeutic priority for people with MS. New treatment should be delayed for 2-4 weeks for vaccination. Where treatment is already ongoing, vaccination against Covid-19 should be administered immediately without disruption of treatment (first-line DMTs, natalizumab, fingolimod), when lymphocytes have recovered sufficiently (cladribine tablets, alemtuzumab) or 4 months after the last dose (ocrelizumab). These recommendations will need to be refined and updated as new clinical evidence in this area emerges.

Potential of Timed 25-Foot Walk Values in Predicting Maximum Walking Distance in Persons with Multiple Sclerosis.

BACKGROUND: Expanded Disability Status Scale (EDSS) scores of 4.0 or greater are determined primarily by maximum walking distance (MWD). Estimation of MWD by persons with multiple sclerosis (MS) is often used due to the impracticality of formally walking a person with MS in a clinic setting. Previous studies have demonstrated discrepancies between estimated and actual MWDs. Whether Timed 25-Foot Walk test (T25FW) values can be used to predict MWD is currently unknown. This study aimed to determine whether T25FW time is predictive of MWD in persons with MS. METHODS: This study is a post hoc analysis of a previously described prospective cohort study. Persons with MS with an EDSS score of 3.5 to 5.5 were included. The participant's T25FW values and MWD were measured. RESULTS: Of the 38 adult participants (mean age, 50.8 years; 27 women [71%]), 24 (63%) had relapsing-remitting MS. The median EDSS score was 4.5 (range, 3.5-5.5). The T25FW times were divided into seven categories (<5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ≥10.0 seconds). The MWDs were divided into corresponding EDSS score categories: ≥500, 300-499, 200-299, 100-199, and ≤99 m. Ordinal logistic regression, when controlled for age, found the T25FW categories to be predictive of EDSS score (χ2 = 17.630, df = 7, P = .014). CONCLUSIONS: The T25FW value may be used as a surrogate estimate of MWD. Further studies are needed to confirm the reliability of the T25FW in predicting MWD.

Behavioral practices of patients with multiple sclerosis during Covid-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in late 2019 and Covid-19, a disease caused by SARS-CoV-2 became a pandemic in March 2020. As the pandemic still unfolds, uncertainty circles around the impact of SARS-CoV-2 infection on patients with chronic diseases, including autoimmune diseases such as multiple sclerosis (MS). To diminish the risk of SARS-CoV-2 infection and lessen the impact of the Covid-19 pandemic on the healthcare of MS patients, it is essential to understand knowledge, attitudes, and various behavioral practices related to Covid-19 among MS patients. Therefore, this study aimed to look at the behavioral practices related to Covid-19 among patients with MS. A total of 176 MS patients diagnosed at least one year before the survey were conveniently sampled online in Saudi Arabia and their data collected using a structured interview questionnaire in electronic Google form. We determined the reliability of the questionnaire by measuring its internal consistency in a pilot sample of 30 participants. Overall, more than 80% of participants had good knowledge and attitudes towards Covid-19. However, this did not correlate well with the impact on healthcare (r = 0.06). Our study revealed that 46% of participants were anxious about taking their medication, and 32% of participants missed their hospital appointments. Furthermore, 15% of the participants had a relapse but did not go to the hospital because of the pandemic, 15.9% stopped their DMTs, and 35.2% missed drug infusions or refills. Our study revealed overall good knowledge and attitudes related to Covid-19 among MS patients. However, the healthcare impact was considerable, as 32% of the participants missed their hospital appointments, and another 15% had a relapse. This highlights the significance of the impact of the Covid-19 pandemic on the healthcare of patients with MS. Measures to mitigate the effect of the pandemic on healthcare service delivery to patients with MS, such as telemedicine, should be strongly encouraged.

Efficacy and Safety of Intravenous Cladribine in Patients with Rapidly Evolving or Early Secondary Progressive Multiple Sclerosis.

Background Multiple sclerosis (MS) is an autoimmune and demyelinating inflammatory disease that affects the central nervous system (CNS). The etiology of the disease remains unknown. Multiple theories highlight genetic, environmental, and infectious factors that may a role. MS is considered as the main cause of disability in young people. Cladribine, known chemically as (2-Chloro-2'-deoxyadenosine), is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas. The goal of this study was to evaluate the safety and efficacy of cladribine in patients with rapidly evolving or early secondary progressive MS. Methods This observational, single-center, retrospective chart review at the MS Clinic in the Ottawa General Hospital, Ottawa, Canada. A total of 24 patients (median Expanded Disability Status Scale (EDSS) of 4.5) received cladribine (0.07 mg/kg/day) for four consecutive days every six months for ≥ 2 cycles with further cycles depending on lymphocyte recovery or disease activity to a maximum of eight cycles from 2005 until 2016 were included. Four patients who were already diagnosed with rapidly evolving or early secondary progressive multiple sclerosis (SPMS) were induced with cladribine. We evaluated relapse, EDSS, and magnetic resonance imaging (MRI) results. Results Out of 24 patients (ages ranging from 30 - 60), 80% were female. Median follow-up time was seven years. The mean relapse rate in the two years before patients were given cladribine was 1.25. Twenty patients had previously received multiple disease-modifying therapies (DMTs) (≥ 2) prior to receiving cladribine. Following cladribine, eight patients suffered 10 relapses (33.3% of the cohort). Annualized relapse rates (ARRs) were reduced from 1.25 to 0.42, which was statistically significant (p-value = 0.002). There was no mean difference in EDSS (p-value = 0.06): 16% deteriorated, 62% did not change, and 12.5% improved. New MRI activity (new T2 or Gad+ lesions) was noted in only seven of 24 patients.  Conclusion Parenteral cladribine reduced the relapse rate from 1.25 to 0.42, which was statistically significant (p-value = 0.002). MRI activity in patients with rapidly evolving or early secondary progressive multiple sclerosis had a reasonable safety profile.

Case Series: Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G-Related Disease Spectrum.

Introduction: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-related disease was initially described as a subtype of neuromyelitis optica spectrum disorder (NMOSD) with antibodies against MOG. However, it has recently been described as a separate disease entity with clinical and radiological features that overlap those of multiple sclerosis (MS) and NMOSD; the clinical features of this disease phenotype remain undetermined. We herein report the clinical presentation of nine MOG-IgG-positive patients, not all of whom fulfill the NMOSD criteria, in order to highlight the features and challenges of this condition. Method: We retrospectively reviewed the records of the London (Ontario) MS clinic to identify patients diagnosed with positive MOG antibodies based on the 2015 NMOSD consensus criteria. Result: Nine patients were identified, all Caucasian. Seven (78%) were female, and the median age of onset was 41 years (range, 28-69 years); the median Expanded Disability Status Scale score at onset was 3.0 (range, 2.0-4.0). A monophasic course was noted in two (22.2%) patients, while the median number of relapse events was 3 (range 2-5) in 77.8% of the patients. Optic neuritis and transverse myelitis contributed equally as initial manifestations in three individuals (33%), while brainstem relapse was reported in two individuals (22%). The brain magnetic resonance imaging findings were compatible with McDonald's 2010 dissemination in space criteria in three cases (33%). Short myelitis and an (H)-sign were each documented in one patient. Conclusion: The phenotypes of MOG Ab-positive cases exhibited overlapping features with MS and NMOSD. This finding highlights the importance of screening for anti-MOG in individuals with demyelinating symptoms, in consideration of the possibility of false-positive MOG Ab results.

Neuromyelitis optica spectrum disorders in Arabian Gulf (NMOAG); establishment and initial characterization of a patient registry.

OBJECTIVE: To describe the clinical and radiological characteristics of neuromyelitis optica spectrum disorders (NMOSD) patients from the Arabian Gulf relative to anti-aquaporin 4 antibody serostatus. METHODS: Retrospective multicentre study of hospital records of patients diagnosed with NMOSD based on 2015 International Panel on NMOSD Diagnosis (IPND) consensus criteria. RESULTS: One hundred forty four patients were evaluated, 64.3% were anti-AQP4 antibody positive. Mean age at onset and disease duration were 31±12 and 7 ±â€¯6 years respectively. Patients were predominantly female (4.7:1). Overall; relapsing course (80%) was more common than monophasic (20%). Optic neuritis was the most frequent presentation (48.6%), regardless of serostatus. The proportion of patients (54.3%) with visual acuity of ≤ 0.1 was higher in the seropositive group (p = 0.018). Primary presenting symptoms of transverse myelitis (TM) were observed in 29% of patients, and were the most significant correlate of hospitalization (p<0.001). Relative to anti-APQ4 serostatus, there were no significant differences in terms of age of onset, course, relapse rates or efficacy outcomes except for oligoclonal bands (OCB), which were more often present in seronegative patients (40% vs.22.5%; p = 0.054). Irrespective of serostatus, several disease modifying therapies were instituted including steroids or immunosuppressives, mostly, rituximab and azathioprine in the cohort irrespective of serostatus. The use of rituximab resulted in reduction in disease activity. CONCLUSION: This is the first descriptive NMOSD cohort in the Arabian Gulf region. Seropositive patients were more prevalent with female predominance. Relapsing course was more common than monophasic. However, anti-AQP4 serostatus did not impact disease duration, relapse rate or therapeutic effectiveness. These findings offer new insights into natural history of NMOSD in patients of the Arabian Gulf and allow comparison with patient populations in different World regions.

Awareness of patients with multiple sclerosis in Saudi Arabia regarding the relationship between smoking and multiple sclerosis.

OBJECTIVE: To assess the awareness of patients with multiple sclerosis about the relationship between smoking and multiple sclerosis in Saudi Arabia. METHODS: A descriptive cross-sectional study was carried out in 2018 for 162 patients who are attending a tertiary hospital in Jeddah, Kingdom of Saudi Arabia. Self-administered questionnaire and telephone-based interview were used to collect the data. The Analysis was carried out through a statistical package for the social sciences (SPSS) software version 21 by using chi-square. RESULTS: A total of 162 patients responded to the questionnaire (response rate, 58.1%). Among the respondents, 56 were current smokers, and 41 of them were males. Thirty-nine patients had a previous cessation attempt, and in 64.1% of the cases, it was mainly a self-made decision. Doctors counseled only 52.7% of the active smokers regarding the effect of smoking on the progression of their disease. CONCLUSION: Results indicate that there a is low level of awareness regarding the risk of smoking on multiple sclerosis. Therefore, educational programs and campaigns would be beneficial to fulfill the gap. Moreover, Health institutions and health care workers should take this issue into account when counseling the patient.

Tolerability and discontinuation rates in teriflunomide-treated patients. A real-world clinical experience.

OBJECTIVE: To assess the real-world tolerability of teriflunomide in multiple sclerosis (MS) patients from a large Canadian MS Centre of Care to determine whether previously treated (PT) patients have different tolerability thresholds than treatment-naive (TN) patients, leading to differing discontinuation rates. METHODS: This non-interventional, single-center, retrospective chart review examined all patients who were prescribed commercial teriflunomide between July 2014 and May 2015 at the MS Clinic in the Ottawa General Hospital and Research Institute, Ottawa, Canada. RESULTS: A total of 119 patient charts were reviewed (29 TN and 90 PT). Overall, 19 (15.9%) patients discontinued teriflunomide after a mean treatment duration of 35 weeks. The most common reason for discontinuation was side effects in 8 patients (42%).Discontinuation due to intolerability alone occurred in 13 patients. The number of discontinuations was not sufficient to demonstrate a statistically significant difference between TN and PT patients (p=0.1). CONCLUSION: This retrospective chart review provides some evidence about the real-world tolerability of teriflunomide. Discontinuations were low overall and consistent with previously reported clinical trial data. There was no significant difference in discontinuation rates between patients in the TN and PT groups. We believe that teriflunomide is a safe and well-tolerated oral alternative to injectable therapies.

Radiologically isolated syndrome: watchful waiting vs. active treatment.

INTRODUCTION: Neurologists are frequently consulted for patients who have white matter lesions discovered incidentally on their brain MRI, performed for reasons other than suspecting a demyelinating disease. The referring physician will question if the person has multiple sclerosis (MS). If the MRI is typical for MS but there are no clinical symptoms or signs suggestive of a demyelinating disorder, patients are diagnosed as having a Radiologically Isolated Syndrome (RIS). Areas covered: This is a timely review on RIS with a focus on treatment considerations. Expert commentary: Multiple studies have tried to identify common predictive factors for conversion of RIS to clinical MS, the strongest thus far being an asymptomatic cervical spinal cord lesion. Treatment of RIS is highly controversial, but early treatment in carefully selected patients might improve long term outcome.