Association between obesity during different age periods and multiple sclerosis in Saudi Arabia: A multicenter case-control study.

OBJECTIVES: To determine whether body size in different age periods is associated with an increased risk of MS in Saudi Arabia. METHODS: This study included 307 MS patients and 307 healthy controls from clinics and hospital wards in three cities (Riyadh, Jeddah, and Dammam) in Saudi Arabia (2016-2017). We used Stunkard's standard body silhouettes to determine the participants' body sizes (from 1 to 9) during different age periods (school levels). We calculated adjusted odds ratios (AORs) and 95% confidence intervals (CIs) and performed multivariable analysis adjusted for age and gender. RESULTS: Large body sizes (silhouettes 6-9) and body size 5 during intermediate school were associated with an increased risk of MS (AOR: 3.75, 95% CI: 1.10-12.78 and AOR: 3.75, 95% CI: 1.41-10, respectively). The smallest body size (1) during intermediate school was associated with a lower risk of MS (AOR: 0.39, 95% CI: 0.17-0.90) compared to body size 3. CONCLUSION: Overweight and obesity during the intermediate school period (ages 13-15 years) are associated with an increased risk of MS, particularly among females.

Cultural acceptance of robotic telestroke medicine among patients and healthcare providers in Saudi Arabia. Results of a pilot study.

OBJECTIVE: To determine the degree of satisfaction and acceptance of stroke patients, their relatives, and healthcare providers toward using telestroke technology in Saudi Arabia. METHODS: A cross-sectional study was conducted between October and December 2012 at King Abdulaziz Medical City, Ministry of National Guard Affairs, Riyadh, Saudi Arabia. The Remote Presence Robot (RPR), the RP-7i (FDA- cleared) provided by InTouch Health was used in the study. Patients and their relatives were informed that the physician would appear through a screen on top of a robotic device, as part of their clinical care. Stroke patients admitted through the emergency department, and their relatives, as well as healthcare providers completed a self-administered satisfaction questionnaire following the telestroke consultation sessions. RESULTS: Fifty participants completed the questionnaire. Most subjects agreed that the remote consultant interview was useful and that the audiovisual component of the intervention was of high quality; 98% agreed that they did not feel shy or embarrassed during the remote interview, were able to understand the instruction of the consultant, and recommended its use in stroke management. Furthermore, 92% agreed or strongly agreed that the use of this technology can efficiently replace the physical presence of a neurologist. CONCLUSION: Results suggest that the use of telestroke medicine is culturally acceptable among stroke patients and their families in Saudi Arabia and favorably received by healthcare providers.

Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring.

BACKGROUND: Natalizumab, a highly specific α4-integrin antagonist, , has recently been registered across the Middle East and North Africa region. It improves clinical and magnetic resonance imaging (MRI) outcomes and reduces the rate of relapse and disability progression in relapsing-remitting multiple sclerosis (MS). Natalizumab is recommended for patients who fail first-line disease-modifying therapy or who have very active disease. Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab. We aim to develop regional recommendations for the selection and monitoring of MS patients to be treated with natalizumab in order to guide local neurological societies. METHODS: After a review of available literature, a group of neurologists with expertise in the management of MS met to discuss the evidence and develop regional recommendations to guide appropriate use of natalizumab in the region. RESULTS: Disease breakthrough is defined as either clinical (relapse or disability progression) or radiological activity (new T2 lesion or gadolinium-enhancing lesions on MRI), or a combination of both. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease based on its established efficacy in Phase III studies. Several factors including prior immunosuppressant therapy, anti-John Cunningham virus (JCV) antibody status and patient choice will affect the selection of natalizumab. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. The anti-JCV antibody test is used to assess anti-JCV antibody status and identify the risk of PML. While seronegative patients should continue treatment with natalizumab, anti-JCV antibody testing every 6 months and annual MRI scans are recommended as part of patient monitoring. In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML. Clinical vigilance and follow-up MRI scans remain the cornerstone of monitoring. After 2 years of natalizumab therapy, monitoring should include more frequent MRI scans (every 3-4 months) for seropositive patients, and the risk-benefit ratio should be reassessed and discussed with patients. CONCLUSIONS: Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

Why HURT? A review of clinical instruments for headache management.

The Global Campaign against Headache, directed by the non-governmental organization Lifting The Burden (LTB) in official relations with the World Health Organization (WHO), aspires to reduce the global burden of headache. Ultimately this calls for improvements in headache management, largely in primary care, where most people with headache receive medical care. In support, LTB is developing a range of headache management aids for primary care. Presently, no single instrument covers the range of assessment and decision-making necessary for successful headache management, and few make the important link between assessment and clinical advice. Expressly to fill this gap, LTB has developed a new instrument: the Headache Under-Response to Treatment (HURT) Questionnaire, an eight-item, self-administered questionnaire addressing headache frequency, disability, medication use and effect, perceptions of headache "control" and knowledge of diagnosis. This instrument is intended not only to evaluate current headache outcomes and assess the need for and response to treatment, but also to provide guidance on appropriate actions towards treatment optimization. The first draft of the HURT was created by an expert consensus group, meeting at WHO headquarters in Geneva, Switzerland. The final version came about through multiple refinements following psychometric testing. Assessment of clinical utility is ongoing in multiple countries.

The immunomodulatory and neuroprotective effects of mesenchymal stem cells (MSCs) in experimental autoimmune encephalomyelitis (EAE): a model of multiple sclerosis (MS).

Mesenchymal stem cells (MSCs) are multipotent cells that differentiate into the mesenchymal lineages of adipocytes, osteocytes and chondrocytes. MSCs can also transdifferentiate and thereby cross lineage barriers, differentiating for example into neurons under certain experimental conditions. MSCs have anti-proliferative, anti-inflammatory and anti-apoptotic effects on neurons. Therefore, MSCs were tested in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), for their effectiveness in modulating the pathogenic process in EAE to develop effective therapies for MS. The data in the literature have shown that MSCs can inhibit the functions of autoreactive T cells in EAE and that this immunomodulation can be neuroprotective. In addition, MSCs can rescue neural cells via a mechanism that is mediated by soluble factors, which provide a suitable environment for neuron regeneration, remyelination and cerebral blood flow improvement. In this review, we discuss the effectiveness of MSCs in modulating the immunopathogenic process and in providing neuroprotection in EAE.

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.

The importance of quality-of-life assessment in the management of patients with multiple sclerosis. Recommendations from the Middle East MS Advisory Group.

Multiple sclerosis (MS) has a major negative impact on patients` health-related quality of life (QoL). A group of MS experts in the Middle East met to develop recommendations for the routine assessment of QoL in patients with MS. The group recommended that patients need to be assessed once a year using the multiple sclerosis international QoL questionnaire (MusiQoL), which is available in Arabic. Assessments should be made when patients are relapse-free to avoid confounding factors. At other clinic visits, patients` QoL should also be monitored, alongside their physical assessment, using open and structured questions on disease features that are likely to affect their QoL. This approach should allow long-term monitoring of key features of MS that are important to patients` well being, and aid decision-making regarding their management, including the use of disease-modifying drugs.

Decidua Basalis Mesenchymal Stem Cells Favor Inflammatory M1 Macrophage Differentiation In Vitro.

Placental mesenchymal stem cells from maternal decidua basalis tissue (DBMSCs) are promising cells for tissue repair because of their multilineage differentiation and ability to protect endothelial cells from injury. Here, we examined DBMSC interaction with macrophages and whether this interaction could modulate the characteristics and functions of these macrophages. We induced monocytes to differentiate into M1-like macrophages in the presence of DBMSCs. DBMSC effects on differentiation were evaluated using microscopy, flow cytometry, and ELISA. DBMSC effects on M1-like macrophage induction of T cell function were also examined. The culture of DBMSCs with monocytes did not inhibit monocyte differentiation into M1-like inflammatory macrophages. This was confirmed by the morphological appearance of M1-like macrophages, increased expression of inflammatory molecules, and reduced expression of anti-inflammatory molecules. In addition, DBMSCs did not interfere with M1-like macrophage phagocytic activity; rather, they induced stimulatory effects of M1-like macrophages on CD4⁺ T cell proliferation and subsequent secretion of inflammatory molecules by T cells. We showed that DBMSCs enhanced the differentiation of M1-like inflammatory macrophages, which function as antitumor cells. Therefore, our findings suggest that DBMSCs are inflammatory cells that could be useful in cancer treatment via the enhancement of M1- like macrophages.

Novel presenilin 1 mutation associated with early-onset Alzheimer`s disease in a Saudi patient.

We report a 60-year-old Saudi patient with the clinical diagnosis of Alzheimer`s disease (AD) and a novel mutation in the presenilin gene. We investigated mutations in the presenilin-1 gene in Saudi patients with AD using polymerase chain reaction and direct DNA sequencing methods. We extracted genomic DNA from the whole blood of both patients and normal control individuals. We sequenced and compared amplicons with the sequences of the respective exons of normal individuals as well as data available in GenBank. We detected a homozygous mutation (g-c) in exon 12, resulting in the missense mutation (Arg377Thr), in the DNA of a 60-year-old patient. We located this mutation in the cytoplasmic loop near the transmembrane domain 7.

Neuromuscular paralysis in the intensive care unit.

OBJECTIVE: To determine the features, causes, risk factors and outcome of acquired neuromuscular paralysis in critically ill patients. METHODS: Retrospective review of all confirmed cases of acquired polyneuropathy and myopathy examined by our Neurology service in the Intensive Care Unit (ICU), at King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia over a period of 5 years. All patients had comprehensive electrophysiological studies and one third had muscle and nerve biopsies. RESULTS: Thirty cases were included, 8 cases of polyneuropathy, 15 cases of myopathy and 7 cases of mixed neuropathy and myopathy. Absent deep tendon reflexes and absent sensory potential on nerve conduction studies were significantly suggestive of neuropathy. The level of creatine phosphokinase was not of great diagnostic value. Most polyneuropathy and myopathy cases had passed through a stormy ICU course with sepsis and multiorgan failure. The use of high doses of steroids was more associated with myopathy. Seven patients died in ICU, the others were discharged to the wards after a mean ventilation period of 40 days. One patient became chronic ventilator dependent. CONCLUSION: From this series and available literature, it seems that symptomatic myopathy is more frequent than polyneuropathy and some risk factors are common for both (sepsis and multiorgan failure) while the use of steroids is more associated with ICU myopathy. Treating sepsis and stopping corticosteroids results in the improvement of most of the cases.

Diabetic neuropathy. Correlation with other diabetic microvascular complications.

OBJECTIVE: We studied the frequency of neuropathy in Saudi patients with definite diabetic microvascular complications and compared it to patients without complications. A high frequency of neuropathy in patients with definite microvascular complications would suggest a vascular etiology. METHODS: The study group consisted of 201 type-2 diabetic patients followed in the diabetic clinic of King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia. These patients were screened for microvascular disease. Only symmetrical distal sensory and motor neuropathy cases were included in the study. Screening for retinopathy was carried out according to Klien`s criteria and nephropathy was diagnosed if albuminuria, microalbuminuria, abnormal blood urea nitrogen or creatinine was present. RESULTS: There was a strong correlation between the prevalence of diabetic peripheral neuropathy, retinopathy (P<0.001) and nephropathy (P<0.01), in patients with type 2 diabetes mellitus. This strong correlation suggests a common underlying pathogenesis. CONCLUSION: We conclude that microangiopathy may be a major factor in the pathogenesis of diabetic neuropathy. Major risk factors for microangiopathy are the degree of glycemic control and duration of diabetes.

Stem cell research and regenerative medicine at King Abdullah International Medical Research Center.

Translation of stem cell research from bench to bedside opens up exciting new therapeutic options for patients. Although stem cell research has progressed rapidly, its clinical applications have not kept pace. We report on the establishment of a stem cell research and regenerative medicine program at King Abdullah International Medical Research Center (KAIMRC). The purpose of this unit is to coordinate advanced stem cell research and translational outcomes with the goal of treating chronic human diseases, such as cancer, diabetes, cardiovascular, neurological, immunological, and liver diseases. Our first step in achieving this goal was to integrate the stem cells and regenerative medicine unit with our umbilical cord blood bank and bone marrow registry. This organizational structure will provide different sources for stem cells for research and clinical purposes, and facilitate our stem cell research and stem cell transplantation program. We are at an early and exciting stage in our program, but we believe that our progress to the international stage will be rapid and have a significant impact.

Public perception and attitude of saudis toward organ and tissue donation.

Biobanks depend on the willingness of people to contribute samples for both research and storage; however, the requirements to perform research on biobanked samples are different than the requirements for their use in organ transplants. The objectives of this study were (1) to characterize public attitudes toward tissue and organ donation for transplantation and biobanking and (2) to identify significant predictors of these attitudes. A cross-sectional study was conducted with a total of 1051 adult subjects, all of whom accompanied their ill relatives to the outpatient clinics at King Abdulaziz Medical City. All subjects were given an interview questionnaire about their previous healthcare experiences and an attitude scale to assess their willingness to participate in organ donation for transplantation or tissue donation for research. A total of 64.7% of all participants reported having a positive attitude toward organ donation, and 68.8% of participants reported having a positive attitude toward biobanking. There was a significant and direct correlation between the attitude score related to organ donation and the attitude score related to tissue donation for research (r = 0.513, P < 0.001). After adjusting for other variables by multiple regression analyses, a positive attitude toward either organ donation or tissue donation for research was significantly more prevalent among females (P < 0.001), those who had previously participated in health-related research (P < 0.001 and P = 0.002, respectively), and those who were aware of organ retention controversies (P = 0.036 and P = 0.001, respectively). Other significant predictors of positive attitudes toward only biobanking were a history of previous blood tests (P = 0.038) and the completion of secondary education (P < 0.001). The attitude of the Saudi public is favorable toward both organ donation and tissue biobanking. Attitudes about the 2 types of donations are related. Previous participation in health-related research and awareness of organ retention controversies are significant predictors of attitudes toward both types of donations.

Prevalence of migraine and non-migraine headache among high school students at the National Guard Housing in Riyadh, Saudi Arabia.

OBJECTIVE: To determine the prevalence of headache and migraine, to identify symptoms that accompany headache attack, and to determine the possible effect of headache on school attendance, among high school students. METHODS: A cross-sectional, questionnaire-based study of secondary school students of the National Guard Housing in Riyadh, Kingdom of Saudi Arabia, was executed during the academic year of 2002 and 2003. A sample of 1750 students was included from 4 schools by systemic random sampling for each school. The questionnaire included demographic data. The second part includes specific questions on headache, and whether there had been headache in the year preceding the survey, type of headache, and its diagnosis according to International Headache Society (IHS) criteria. Possible effect of headache on school attendance was recorded. RESULTS: Approximately one-third of the entire study sample had recurrent headache episodes not related to febrile illness in the year preceding the survey. Female students showed a significantly higher prevalence than males of migraine, as well as non-migraine headache, with the least prevalence among the younger students of ages 16-17 years. More than one-third of all students were absent from school due to headache. CONCLUSION: Recurrent headache is prevalent among the high school students, and more among female students. These prevalence rates are comparable with those reported elsewhere. Health education sessions at schools, primary care clinics, and the society in general are recommended to increase awareness for this common adolescent's neurological problem.