Role of fenofibrate in multiple sclerosis.

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the central nervous system (CNS). The underlying pathophysiology of MS is the destruction of myelin sheath by immune cells. The formation of myelin plaques, inflammation, and injury of neuronal myelin sheath characterizes its neuropathology. MS plaques are multiple focal regions of demyelination disseminated in the brain's white matter, spinal cords, deep grey matter, and cerebral cortex. Fenofibrate is a peroxisome proliferative activated receptor alpha (PPAR-α) that attenuates the inflammatory reactions in MS. Fenofibrate inhibits differentiation of Th17 by inhibiting the expression of pro-inflammatory signaling. According to these findings, this review intended to illuminate the mechanistic immunoinflammatory role of fenofibrate in mitigating MS neuropathology. In conclusion, fenofibrate can attenuate MS neuropathology by modulating different pathways, including oxidative stress, autophagy, mitochondrial dysfunction, inflammatory-signaling pathways, and neuroinflammation.

Life-Saving Treatments for Spinal Muscular Atrophy: Global Access and Availability.

Background and Objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disorder manifesting with progressive muscle weakness and atrophy. SMA type 1 used to be fatal within the first 2 years of life, but is now treatable with therapies targeting splicing modification and gene replacement. Nusinersen, risdiplam, and onasemnogene abeparvovec-xioi improve survival, motor strength, endurance, and ability to thrive, allowing many patients to potentially attain a normal life; all have been recently approved by major regulatory agencies. Although these therapies have revolutionized the world of SMA, they are associated with a high economic burden, and access to these therapies is limited in some countries. The primary objective of this study was to compare the availability and implementation of treatment of SMA from different regions of the world. Methods: In this qualitative study, we surveyed health care providers from 21 countries regarding their experiences caring for patients with SMA. The main outcome measures were provider survey responses on newborn screening, drug availability/access, barriers to treatment, and related questions. Results: Twenty-four providers from 21 countries with decades of experience (mean 26 years) in treating patients with SMA responded to the survey. Nusinersen was the most available therapy for SMA. Our survey showed that while genetic testing is usually available, newborn screening is still unavailable in many countries. The provider-reported treatment cost also varied between countries, and economic burden was a major barrier in treating patients with SMA. Discussion: Overall, this survey highlights the global inequality in managing patients with SMA. The spread of newborn screening is essential in ensuring improved access to care for patients with SMA. With the advancement of neurotherapeutics, more genetic diseases will soon be treatable, and addressing the global inequality in clinical care will require novel approaches to mitigate such inequality in the future.

The prevalence of major depression and generalized anxiety disorder in patients with multiple sclerosis in Saudi Arabia: a cross-sectional multicentered study.

Background: Multiple sclerosis (MS) is an autoimmune disease characterized by chronic, progressive neurodegeneration of the central nervous system (CNS), and it is the most common inflammatory neurological disease affecting young adults. Given the chronic, progressive nature of the disease, psychiatric disorders are more prevalent among these patients, as reported in the literature; however, data in Saudi Arabia are limited. This study aimed to estimate the prevalence of major depression and generalized anxiety disorder in patients with MS and their association with different patient demographics. Methods: This was a cross-sectional, multicentered study that included adult patients with MS from 30 June 2021 to 30 June 2022. Participants were interviewed in person and asked to complete a survey that included general demographics, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) questionnaire. Other variables related to the patients' conditions, such as MS type and Expanded Disability Status Scale (EDSS) score, were collected from the patient's electronic records. Descriptive statistics were performed, and associations were made using the chi-square, Fisher's exact, and analysis of variance tests, as appropriate. Results: A total of 192 participants were included in this study. Based on a cutoff score of >10 on the GAD-7 and PHQ-9 scales, the prevalence of generalized anxiety disorder was 26.1% (50), with the majority of participants having minimal anxiety (40%); meanwhile, the prevalence of major depression was 42.7% (n = 82), and most of them had mild depression (30%). Female participants scored significantly higher compared to men on the GAD-7 scale (p = 0.0376), but not on the PHQ-9 scale (p = 0.1134). In addition, no statistically significant association was detected between functional disability (EDSS score) and prevalence of anxiety and depression. Conclusion: This study demonstrated a high prevalence of generalized anxiety disorder and major depression among patients with MS compared with that in the general population, with women being more affected. As these comorbid disorders could negatively affect the disease course, screening is of paramount significance.

Exploring the outcome of multiple sclerosis among Saudi adult patients. A single-centered cross-sectional study at King Abdulaziz Medical City in Riyadh, Saudi Arabia.

OBJECTIVE: To assess the outcome and impact of multiple sclerosis (MS) using validated Arabic versions of the Barthel index (BI) multiple sclerosis impact scale (MSIS-29), the modified Rankin scale (mRS), and the expanded disability status scale (EDSS). METHODS: A cross-sectional study conducted at King Abdulaziz Medical City in Riyadh, Kingdom of Saudi Arabia, during July-November 2017. All Saudi adult patients diagnosed with MS between 2000-2016 (269 patients) were included. Patients were contacted via phone calls and were assessed using a newly developed and validated multi-component questionnaire that included demographic data, disease course, and Arabic versions of the scales RESULTS: Out of 269 patients, 210 (78.2%) responded. The average patient age was 37.44+/-10.3 years. The majority were females (69.5%). Only, 51 (24.3%) patients reported worsening conditions. Annually, the average relapse rate was 2.28+/-1.91. In regard to patient outcomes, 120 (57.1%) showed no significant disability in mRS, 146 (69.5%) were ambulatory without aid in EDSS, and 185 (89.4%) were independent in BI scores. The average MSIS-29-PHYS score was 33.6+/-27.6 and MSIS-29-PSYCH score was 38.2+/-25.8. Modified Rankin scale and EDSS were significantly associated with the current use of disease-modifying therapy (DMT). Modified Rankin scale was negatively associated with delayed diagnosis. Barthel index showed significant association with medication compliance and the absence of attacks. CONCLUSION: Majority of patients had a favorable outcome that was linked with the use of DMT, compliance, early diagnosis, and absence of attacks.

Renal dysfunction as a predictor of acute stroke outcomes.

OBJECTIVE: To explore if renal dysfunction in terms of estimated glomerular filtration rate (eGFR) can be considered a risk factor for stroke outcomes. METHODS: The study population consisted of adults diagnosed with acute stroke admitted to the King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia between 2012 and 2015. Data was collected by chart review. The Modification of Diet in Renal Disease equation was used to estimate GFR. Patients were classified into 2 eGFR categories: eGFR more than 60 (normal) and eGFR less than or equal 60 (low). RESULTS: A total of 727 patients were studied of whom 596 (82%) had normal eGFR and 131 (18%) had low eGFR. There were more males (68.5%). Ischemic strokes were more prevalent (87.2%). Urinary tract infections were more likely to occur in the low eGFR group (OR=2.047, 95% CI=1.024 - 4.093). They were also significantly more likely to die during admission (OR=3.772, 95% CI=1.609-8.844). There was a statistically significant degree of disability reflected by higher mRS (p=0.010) as well as higher post-stroke National Institute of Health Stroke Score scores in the low eGFR group (p=0.011). CONCLUSION: Estimated glomerular filtration rate is a possible predictor of stroke severity, disability and mortality.

Spinal Cord Schistosomiasis: Two Different Outcomes.

Spinal cord schistosomiasis is difficult to diagnose in nonendemic areas. We report the clinical profile of 2 young Saudi males who presented with myelopathy. The first patient arrived at our hospital relatively late, i.e. 3 months following the presentation of initial symptoms, and had received both pulse steroid therapy and a plasma exchange. Praziquantel was administered late and the patient did not recover. The second case presented early, i.e. within around 8 weeks of initial symptoms. This patient received praziquantel without any kind of steroid and had a complete recovery. We concluded that prompt recognition and early treatment with praziquantel is crucial for a better outcome. The role of steroids in these cases still needs to be proven.

Clinical and genetic features of anoctaminopathy in Saudi Arabia.

OBJECTIVE: Characterization of the phenotypic, pathological, radiological, and genetic findings in 2 Saudi Arabian families with anoctaminopathies, and limb girdle muscular dystrophy type 2L (LGMD2L). METHODS: Over a 2-year period from December 2010 to January 2013, the clinical presentations were analyzed and all genes responsible for limb girdle muscular dystrophy (LGMD) were screened in families seen at King Faisal Specialist Hospital and Research Centre, a tertiary care hospital in Riyadh, Saudi Arabia. Out of 66 families with LGMD, we identified 2 families (3.1%) with anoctaminopathy, ANO5 muscular dystrophy. RESULTS: In the first case, a man presented with asymmetrical calves` muscles weakness and atrophy, which was first noted at age 39. The creatinine kinase (CK) level was >20x normal, muscle biopsy showed necrotizing myopathic changes, and an MRI of the legs showed fatty-tissue replacement to muscle tissue with volume loss involving the gastrocnemius and soleus muscles in an asymmetrical fashion. Minimal disease progression was noted over 18 years of follow up. Exercise induced recurrent rhabdomyolysis was noted over the last 2 years. A novel ANO5 gene mutation (Arg58Trp) was found. In the second family, a male presented at the age of 41 with asymptomatic hyperCkemia and intermittent dyspnea. Over 10 years follow up, he became disabled with muscle cramps, rhabdomyolysis, my oglobinurea, and difficulty ambulating. Muscle biopsy showed necrotizing myopathy and perivascular and interstitial amyloid deposit in skeletal muscle. A homozygous deletion of 11.9 Kb encompassing exon 13 to exon 17 was found in the ANO5 gene. Full cardiac investigations were normal in both patients. CONCLUSION: The prevalence of LGMD2L is approximately 3.1% in a Saudi Arabian native LGMD cohort. Slowly progressive, late onset, and asymmetrical weakness was the salient features in these 2 families. The genetic findings were novel and will add to the spectrum of ANO5 known mutations.

Factors potentially influencing academic performance among medical students.

BACKGROUND: Studies are needed to examine predictors of success in medical school. The aim of this work is to explore factors that potentially influence excellence of medical students. METHODS: The study was conducted in the Medical Faculty of King Abdulaziz University during October 2012. A self-administered questionnaire was used. Medical students with a grade point average (GPA) ≥4.5 (out of 5) were included and compared to randomly selected medical students with a GPA <4.5, who were available at the time of the study. RESULTS: A total of 359 undergraduate students participated in the study. 50.4% of the sample was students with a GPA ≥4.5. No statistically significant difference regarding the time spent on outings and social events was found. However, 60.7% of high GPA students spend less than 2 hours on social networking per day as compared to 42.6% of the lower GPA students (P<0.01). In addition, 79% of high GPA students prefer to study alone (P=0.02), 68.0% required silence and no interruptions during studying time (P=0.013), and 47% revise their material at least once before an exam (P=0.02). CONCLUSION: Excellent medical students have many different characteristics. For example, they do not use social networking for prolonged periods of time, and they have strong motivation and study enjoyment. Further studies are needed to examine whether these differences have a real impact on GPA or not.

Neurophobia among medical students.

OBJECTIVE: To assess the attitude of medical students and junior physicians toward neurology. METHODS: A self-administered, previously validated, questionnaire was distributed among 422 students and junior physicians at King Abdulaziz University, Jeddah, Saudi Arabia from September to December 2012. In this cross-sectional study, the questionnaire included demographic data and 12 statements to examine attitudes toward neurology using a Likert scale. RESULTS: The response rate among participants was 70.3%. The mean age was 22.35 (SD+/-1.28) years. Males comprised 46.2%. While 31.3% of students had not decided regarding their future career, 11.8% selected neurology as their first possible choice. Whereas 29.6% of students were not satisfied with their neurology teaching experience, 84.4% found neurology difficult, and 42.7% of the whole group thought that their neuroscience knowledge was insufficient. Advanced clinical year students (namely, interns) were less likely to consider neurology as a career choice (p=0.001). CONCLUSION: Most of the students had an unfavorable attitude toward neurology on the Likert scale. New strategies are needed to change students` attitude toward this demanding specialty.

The impact of `admit no bed` and long boarding times in the emergency department on stroke outcome.

OBJECTIVES: To examine and test the possible association between boarding time and stroke patients` outcome. METHODS: This study is a retrospective review of stroke patients presenting to the Emergency Department (ED) of King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia from 2007-2010. We excluded thrombolysis cases and those deemed critically ill. We collected time of stroke onset, ED arrival, decision to admit, and arrival to ward. Boarding time (BT) was defined as time of arrival to ward minus time of decision to admit. Primary outcome (PO) was defined as a composite of mortality, and/or any of post-stroke complications. RESULTS: We included 300 patients with a mean age +/- standard deviation of 69 +/- 12 years, and 66.3% were men. The PO occurred in 37.7%. There was no association between BT and PO (odds ratio [OR]=0.9, p=0.3), or any of the secondary outcomes, such as, death (OR=0.97, p=0.5), severe disability (OR=0.97, p=0.3), pneumonia (OR=1, p=0.9), urinary tract infection (OR=1, p=0.9), or neurological deterioration (OR=0.8, p=0.1). Multivariate analysis included gender, age, stroke severity, subtype, hypertension, diabetes, coronary disease, atrial fibrillation, heart failure (HF), onset to ED, BT and ED wait time; only moderate to severe stroke, HF, and previous stroke predicted poor outcome. CONCLUSION: Although `admit no bed` was not associated with adverse effects, the results should be interpreted with caution, and early admission to the stroke unit should be encouraged.

A child with leukemia and behavioral changes.

A 12-year-old Saudi girl, known case of T-cell leukemia with CNS relapse. She was diagnosed 2 years ago. Multiple cycles of chemotherapy had been used (Fludarabine, Cytarabine, Methotrexate, Cyclosporine, and Mercaptopurine). She was admitted electively for cord blood transplantation. Afterward, she developed visual, and behavioral change followed by seizure.

Isolated lateral rectus myositis.

Orbital myositis is a rare non-granulomatous inflammatory process within the orbit. Grave's disease and lymphoproliferative disorders are considered the most common cause of orbital myositis. The idiopathic form should be considered after exclusion of known causes or associations. Isolated orbital myositis is a very rare form of this disease. We report a case of an isolated lateral rectus myositis to draw the attention of physicians to this condition, as prompt treatment in our patient resulted in complete recovery.

Guillain-Barre syndrome following cardiac surgery. Difficult diagnosis in the intensive care unit.

Weakness of limb and respiratory muscles developing in the course of treatment in the intensive care unit (ICU) is commonly due to critical illness polyneuropathy, a complication of sepsis, or critical illness myopathy, a complication of the use of neuromuscular blocking agents and steroids. Guillain-Barre syndrome may rarely occur in this setting. We report 2 patients identified in our ICU in the last 20 years. Surgery was an apparent precipitating event in both patients. The clinical, electrophysiological, and cerebrospinal fluid features were consistent with this diagnosis. Both patients responded to treatment; the first case was treated with plasmapheresis while the other with intravenous immune globulin. Thus, while rare, it is important to identify this disorder in the ICU because of its response to specific treatment.