L-2-hydroxyglutaric aciduria: a report of clinical, radiological, and genetic characteristics of two siblings from Egypt.

L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare autosomal recessive disease characterized by elevated levels of hydroxyglutaric acid in the body fluids and brain with abnormal white matter. We present two siblings with psychomotor retardation and quadriparesis. Their brain imaging showed diffuse bilateral symmetrical involvement of the cerebral cortex, white matter, basal ganglia and cerebellum. The whole exome sequence studies revealed a homozygous likely pathogenic variant on chromosome 14q22.1 (NM_024884.2: c.178G > A; pGly60Arg) in the gene encoding for L-2-hydroxyglutarate dehydrogenase (L2HGDH) (OMIM #236792). Therefore, using the L2HGDH gene study is beneficial for L2HGA diagnosis.

Dual antiplatelet therapy versus intravenous tissue plasminogen activator with acute minor ischemic stroke: A systematic review and meta-analysis of safety and efficacy.

OBJECTIVES: To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS). MATERIALS AND METHODS: Following Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale. RESULTS: This meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001). CONCLUSIONS: Our meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.

Prevalence and correlates of fatigue in amyotrophic lateral sclerosis: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS). METHODS: Three databases were searched up to 2nd May 2023 to identify studies reporting fatigue frequency in ALS. Studies included had to identify ALS patients through one of ALS diagnostic criteria and measure fatigue by a validated tool with a specific cut-off value. Meta-analysis was conducted using RStudio's "meta" package with a random-effects model. Subgroup analyses and meta-regression explored the relationship between fatigue frequency in ALS and different covariates. RESULTS: Eleven studies, compromising 1072 patients, met the inclusion criteria and were included in our analysis. The pooled frequency of fatigue across all studies was 48% (95% CI = 40% to 57%). Our subgroup analysis based on the ALSFRS-R revealed a higher frequency of fatigue in studies with lower scores (< 30) compared to those with higher scores (≥ 30), with a pooled frequency of 62% (95% CI = 43% to 79%) and 43% (95% CI = 37% to 49%), respectively. Also, the meta-regression analysis showed a significant negative association between fatigue and ALSFRS-R mean (P = 0.02). The included studies reported an association between fatigue and lower functional status and poorer quality of life in patients with ALS. CONCLUSION: Our findings suggest that fatigue is prevalent in almost half of ALS patients and is associated with lower functional status and poorer quality of life, highlighting the importance of assessing and managing fatigue in ALS patients.

Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence.

OBJECTIVES: Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by modulating key pathways implicated in neurodegeneration. This scoping review aimed to summarize the current evidence of masitinib's neuroprotective activities from preclinical to clinical studies. METHODS: This scoping review was conducted following the guidelines described by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria covered all original studies reporting on the neuroprotective effects of masitinib, including clinical studies, animal studies, and in vitro studies. RESULTS: A total of 16 studies met the inclusion criteria and were included in the review. These comprised five randomized controlled trials (RCTs), one post-hoc analysis study, one case report, and nine animal studies. The RCTs focused on Alzheimer's disease (two studies), multiple sclerosis (two studies), and amyotrophic lateral sclerosis (one study). Across all included studies, masitinib consistently demonstrated neuroprotective properties. However, the majority of RCTs reported concerns regarding the safety profile of masitinib. Preclinical studies revealed the neuroprotective mechanisms of masitinib, which include inhibition of certain kinases interfering with cell proliferation and survival, reduction of neuroinflammation, and exhibition of antioxidant activity. CONCLUSION: The current evidence suggests a promising therapeutic benefit of masitinib in neurodegenerative diseases. However, further research is necessary to validate and expand upon these findings, particularly regarding the precise mechanisms through which masitinib exerts its therapeutic effects. Future studies should also focus on addressing the safety concerns associated with masitinib use.

Association of serum leptin and ghrelin levels with smoking status on body weight: a systematic review and meta-analysis.

Background and aims: Smoking cigarettes is a major global health problem that affects appetite and weight. The aim of this systematic review was to determine how smoking affected plasma leptin and ghrelin levels. Methods: A comprehensive search of PubMed, Scopus, Web of Science, and Ovid was conducted using a well-established methodology to gather all related publications. Results: A total of 40 studies were included in the analysis of 11,336 patients. The overall effect showed a with a mean difference (MD) of -1.92[95%CI; -2.63: -1.20] and p = 0.00001. Subgroup analysis by study design revealed significant differences as well, but with high heterogeneity within the subgroups (I2 of 82.3%). Subgroup by sex showed that there was a significant difference in mean difference between the smoking and non-smoking groups for males (MD = -5.75[95% CI; -8.73: -2.77], p = 0.0002) but not for females (MD = -3.04[95% CI; -6.6:0.54], p = 0.10). Healthy, pregnant, diabetic and CVD subgroups found significant differences in the healthy (MD = -1.74[95% CI; -03.13: -0.35], p = 0.01) and diabetic (MD = -7.69[95% CI, -1.64: -0.73], p = 0.03). subgroups, but not in the pregnant or cardiovascular disease subgroups. On the other hand, the meta-analysis found no statistically significant difference in Ghrelin serum concentration between smokers and non-smokers (MD = 0.52[95% CI, -0.60:1.63], p = 0.36) and observed heterogeneity in the studies (I2 = 68%). Conclusion: This study demonstrates a correlation between smoking and serum leptin/ghrelin levels, which explains smoking's effect on body weight. Systematic review registration: https://www.crd.york.ac.uk/ prospero/display_record.php, identifier (Record ID=326680).

The Role of RIN3 Gene in Alzheimer's Disease Pathogenesis: a Comprehensive Review.

Alzheimer's disease (AD) is a globally prevalent form of dementia that impacts diverse populations and is characterized by progressive neurodegeneration and impairments in executive memory. Although the exact mechanisms underlying AD pathogenesis remain unclear, it is commonly accepted that the aggregation of misfolded proteins, such as amyloid plaques and neurofibrillary tau tangles, plays a critical role. Additionally, AD is a multifactorial condition influenced by various genetic factors and can manifest as either early-onset AD (EOAD) or late-onset AD (LOAD), each associated with specific gene variants. One gene of particular interest in both EOAD and LOAD is RIN3, a guanine nucleotide exchange factor. This gene plays a multifaceted role in AD pathogenesis. Firstly, upregulation of RIN3 can result in endosomal enlargement and dysfunction, thereby facilitating the accumulation of beta-amyloid (Aß) peptides in the brain. Secondly, RIN3 has been shown to impact the PICLAM pathway, affecting transcytosis across the blood-brain barrier. Lastly, RIN3 has implications for immune-mediated responses, notably through its influence on the PTK2B gene. This review aims to provide a concise overview of AD and delve into the role of the RIN3 gene in its pathogenesis.

Restless legs syndrome in multiple sclerosis patients: Prevalence, impact, and association with disease-modifying therapies in a Saudi Arabian pilot study.

BACKGROUND: Restless legs syndrome (RLS) emerges as a notable sleep disorder characterized by distressing sensations within the lower extremities. Its prevalence appears to be higher among patients afflicted with multiple sclerosis (MS) compared to the general population. Despite this observation, the understanding of the intricacies of RLS and its repercussions within the context of MS patients in Saudi Arabia remains limited. METHODS: Employing a cross-sectional design, a comprehensive investigation was undertaken at King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia, spanning from November 2021 to March 2022. A cohort of 66 individuals diagnosed with MS was recruited and subjected to an assessment for RLS employing the revised diagnostic criteria outlined by the International Restless Legs Syndrome Study Group (IRLSSG). Furthermore, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Sleepiness Scale were employed to gage the extent of RLS's impact on sleep quality and daily functioning. RESULTS: The prevalence of RLS amidst the MS cohort was determined to be 30.4%. An observable association was discerned between RLS presence and higher scores on the Expanded Disability Status Scale (p < 0.001), along with diminished sleep quality scores (p < 0.001) and elevated fatigue scores based on IRLSSG criteria (p < 0.001). Within the studied MS cases, 98.5 % exhibited the relapsing-remitting subtype. Further investigation demonstrated that patients treated with Fingolimod or Ocrevus presented normal IRLSSG scores, whereas those undergoing Rituximab treatment manifested an even distribution between normal and moderate scores. Correspondingly, patients receiving interferons showcased 72.2 % with normal scores and 27.8 % with mild scores. Notably, a statistically significant variance in IRLSSG scores was observed when contrasting Fingolimod and Aubagio treatments (P < 0.001). CONCLUSION: The presence of RLS as a comorbidity in MS patients within the Saudi Arabian context emerges as a significant finding, exerting a discernible detrimental influence on both disability status and sleep quality. This study underscores the need for further investigations aimed at unraveling the intricate pathophysiological underpinnings, identification of risk factors, and exploration of therapeutic modalities for RLS in this population. Furthermore, additional research endeavors are warranted to elucidate the diverse impact of various disease-modifying therapies on clinical outcomes.

Special considerations and pitfalls for intracerebral bleeding followed COVID-19 case treated by ECMO.

COVID-19, or coronavirus infection, is an acute respiratory illness caused by the corona virus that can develop into a life-threatening form of ARDS. Extracorporeal membrane oxygenation (ECMO) is a highly effective treatment for life-threatening instances. One of the many complications associated with ECMO was bleeding. COVID patients are at risk for intracerebral bleeding due to several factors, including the drug's action on ACE2 receptors, leading to hypertension, as well as hypercoagulability, dysregulated immune response, DIC, and the use of anticoagulants.

Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study provides a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the safety and efficacy of lithium in amyotrophic lateral sclerosis (ALS) patients. METHODS: PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Your Journals@Ovid were searched up to 9 December 2022. RCTs investigating lithium, either alone or with any supplement, in ALS patients were included. Meta-analysis was performed using RevMan and results are presented in forest plot. RESULTS: Four RCTs with 469 patients met the inclusion criteria and were included in our study. Lithium doses varied among the included studies and one study used a combined therapy of lithium with valproate. Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio = 1.13, 95% confidence interval: 0.73 to 1.75, P = 0.58). No significant differences were observed with regard to survival rate between the two groups (hazard ratio = 0.95, 95% confidence interval: 0.65 to 1.37, P = 0.77). There were also no significant differences between the two groups with regard to average changes of revised amyotrophic lateral sclerosis functional rating scale (P = 0.35) and forced vital capacity percentage predicted (P = 0.73). Subgroup analysis showed no significant differences regarding all investigated outcomes either for lithium alone or lithium with valproate. CONCLUSION: Current evidence suggests a safety profile with no benefit of lithium for ALS. However, given the limited number of RCTs and the safety findings, we recommend further well-designed RCTs to investigate lithium and valproate in ALS patients.

Gaming behavior disorder and its association with social phobia during COVID-19 pandemic: A cross-sectional study among the young Arabs.

Background: Gaming addiction is a compulsive mental health condition that can have severe negative consequences on a person's life. As online gaming has increased during the COVID-19 pandemic, studies have shown a heightened risk of mental health issues. This study aims to assess the prevalence of severe phobia and addiction to online gaming among Arab adolescents and identify risk factors associated with these disorders. Methods: This cross-sectional study was conducted across 11 Arab nations. Participants were recruited using convenience sampling through an online survey distributed on social media platforms in 11 Arab countries. The survey included demographic questions, the Nine-item Internet Gaming Disorder Scale-Short Form (IGDS-SF9) to measure participants' online gaming addiction, the Social Phobia Scale (SPS), and questions assessing the impact of the COVID-19 pandemic on the prevalence of internet gaming addiction. The data were analyzed using SPSS win statistical package version 26. Results: Out of 2,458 participants, 2,237 were included in the sample due to non-response and missing data. The average age of the participants was 19.9 ± 4.8 years, and the majority were Egyptian and unmarried. 69% of the participants reported playing more than usual since the COVID-19 pandemic, as they were confined to their homes. Higher social phobia scores were associated with being single, male, and Egyptian. Participants from Egypt and those who felt that the pandemic significantly increased their gaming time had higher scores for online gaming addiction. Several major criteria, such as playing hours per day and beginning gaming at an early age, were associated with a higher level of online gaming addiction with social phobia. Conclusion: The study's findings suggest that there is a high prevalence of internet gaming addiction among Arab adolescents and young adults who play online games. The results also indicate a significant association between social phobia and several sociodemographic factors, which may inform future interventions and treatments for individuals with gaming addiction and social phobia.

Clinical Characteristics, Course, and Outcomes of Vertebral Artery Dissections in the Postpartum Period; a Pooled Analysis of Published Case Reports.

Introduction: Vertebral artery dissection (VAD) is a rare, but life-threatening condition. Compared to the general population, pregnant and postpartum women are more likely to develop VAD. Spontaneous arterial dissections have an ambiguous pathophysiology and may be difficult to manage. This study aimed to pool and analyze the data of published cases in this regard. Methods: We conducted a literature search on February 24, 2022, using MeSH terms of interest in PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases to find studies on VAD following childbirth. Results: A total of 28 studies were included in this review based on a database search. In the studies, 44 postpartum VAD (PPVAD) patients with a mean age of 34.26 ± 3.5 years were included. It took an average of 24.37± 13.7 days from delivery to dissection. 64% of the patients had developed unilateral dissection and 36% had developed bilateral dissection; 70% reported full recovery, and 9% did not achieve full recovery. The most common symptoms were headaches (89%), neck pain (64%), and hypertension (52%). The most common methods of diagnosis were magnetic resonance imaging (MRI) (64%) and computed tomography (CT) angiography (CTA) scan (66%). Only 8 (18%) cases reported the use of electrocardiography (ECG). The recorded outcomes of the patients with unilateral and bilateral postpartum VAD showed no statistical difference. Most of the included studies recommend early suspension and management for a better prognosis and prevention of complications. Conclusion: PPVAD is a severe medical condition but most cases were fully recovered after an early and proper antithrombotic plan for each case scenario.

COVID-19-Associated Cerebrovascular Events: A Case Series Study and a Literature Review of Possible Mechanisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects multiple body systems, including the nervous system. Cerebrovascular accidents can also occur. Patients with comorbid illnesses have severe manifestations and poor outcomes. Despite the proper mechanism of SARS-CoV-2 infection-associated stroke having not yet been settled, various possible mechanisms have been hypothesized. One possibility is that the virus causes endothelial dysfunction and immune-mediated injury. Another possibility is that the trans-neuronal spread of the virus affects brain tissue. In addition, hypercoagulability caused by SARS-CoV-2 infection could lead to a stroke. A virus-induced dysfunction of the renin-angiotensin system could also lead to a stroke. The immune response and vasculitis resulting from SARS-CoV-2 infection are also possible causes via a cytokine storm, immune dysfunction, and various inflammatory responses. SARS-CoV-2 infection may affect calcitonin gene-related peptides and cerebral blood flow and may lead to stroke. Finally, SARS-CoV-2 may cause hemorrhagic strokes via mechanisms stimulated by its interaction with angiotensin-converting enzyme 2 (ACE2), leading to arterial wall damage and blood pressure changes. In this article, we will present seven cases of stroke-associated SARS-CoV-2 infection.

Intracerebral hemorrhage associated COVID-19 patient with normal coagulation profile after ECMO treatment: A case report.

Objective: Coronavirus disease 2019 (COVID-19) is a novel coronavirus-caused infectious acute respiratory disease that can progress to severe acute respiratory distress syndrome (ARDS). For severe cases, extracorporeal membrane oxygenation (ECMO) is an excellent treatment option. ECMO had a number of side effects, including bleeding. Intracerebral hemorrhage can occur in COVID patients due to a variety of mechanisms, including covid's effect on ACE-2 receptors and subsequent hypertension, coagulopathy, DIC, or medication, such as anticoagulant use. Case presentation: We present a case of a 53-year-old male COVID-19 patient who developed multiple, massive, severe intracerebral hemorrhages (ICH) despite a normal coagulation profile after ECMO treatment. Conclusion: COVID-19 can progress to severe acute respiratory distress syndrome (ARDS), necessitating the use of extracorporeal membrane oxygenation (ECMO). Although ICH is not a common complication in patients with COVID-19 disease, it is unknown why this patient had a lower threshold of ICH despite having a normal coagulation profile.

A rare case of Takotsubo syndrome with ventricular septal rupture: Case report.

INTRODUCTION: Takotsubo cardiomyopathy (TCM) mimics acute coronary syndrome and is characterized by reversible left ventricular (LV) apical ballooning in the absence of angiographically substantial coronary artery stenosis. PATIENT CONCERNS: A 31-year-old man with acute dejection, physical stress, and psychological strain from the dread of losing his work arrived at the emergency department with chest pain, and discomfort that had lasted 3 hours. DIAGNOSIS: Once the coronary angiography revealed normal epicardial coronaries, the case was retroactively diagnosed, and the levels of cardiac enzymes were increased. INTERVENTIONS: The amount of necrotic tissue was so little that the surgeon could only verbally convey it. It is completely closed with the help of a Dacron sheet. The patient received surgical closure of the VSR a few days after having a surgical consultation. OUTCOMES: No postoperative echocardiogram was required, and the patient was sent home in great general condition. CONCLUSION: The presence of TCM with a ruptured LV wall was extremely rare because our patient had neither clinical risk indicators nor a family history of coronary artery disease. As a Takotsubo syndrome severe complication, we underline the significance of identifying, diagnosing, and treating it.

Could the New BA.2.75 Sub-Variant Cause the Emergence of a Global Epidemic of COVID-19? A Scoping Review.

With over 58 million cases and 6 million deaths by August 2022, the Coronavirus disease 2019 (COVID-19), causing severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2), has had an insurmountable impact on the world's population. This is one of the worst health crises since 1918's influenza pandemic. There are four subvariants of Omicron; BA.1, BA.1.1, BA.2 and BA.3. As a result of new mutations in its spike protein, most of which occur in its receptor binding site, the Omicron variant appears to be more transmissible and less resistant to vaccination and antibody response. Understanding Omicron's virology and mutations is essential to developing diagnostic and therapeutic methods. A thorough assessment of control measures, as well as timely adjustment of control measures, requires addressing such issues as re-infection risk, vaccine response, booster vaccine doses, and the increased rate of Omicron infections. This review article aims to look at the current information about the different types of SARs-CoV-2, focusing on the new subtype BA.2.75.

Successful use of therapeutic anticoagulation therapy in two patients with moderate stroke from the second day of onset: A case report and literature review.

Introduction and importance: Hemorrhagic transformation of ischemic stroke is one of the most traumatic consequences of ischemic stroke. Therefore, deciding the optimal time for anticoagulant application and its effect on clinical outcome, recurrence and risk for hemorrhagic transformation are still in quarry. The European Heart Rhythm Association recommends the usage of anticoagulants after 3-4 days after a mild stroke, 6 days after moderate stroke and 12 days after a severe stroke. Case presentation: In our case report, we present two patients who started full therapeutic anticoagulation of low molecular weight heparin from the first day after moderate ischemic stroke, warfarin was added later guided by INR and discharged on oral anticoagulants for associated AF. They improved clinically with improved motor function for both upper and lower limbs, sensation and gaze without any complication followed by serial CT. Clinical discussion and conclusion: As a result of this case report, clinical improvement has not been associated with hemorrhagic sequelae of anticoagulant administration on the first day. At this point, we recommend conducting a trial to study the effect of early application of anticoagulants from the first day on clinical outcome, recurrence, and hemorrhagic transfusion of stroke.

Amoebic Hepato-Pericardial Fistula Complicating Amoebic Liver Abscess Treated With Pericardiotomy: A Case Report.

Parasitic infections like amoebiasis are often asymptomatic in the tropics, but the invasive disease can cause an amoebic liver abscess. During pericardiocentesis, amoebiasis is more noticeable in left lobe abscesses with chocolate-like pus drainage. Here, we present an unusual amoebic liver abscess that erupted into the pericardial cavity via a diaphragmatic fistula. An emergency pericardiotomy was performed to relieve cardiac tamponade, and the liver abscess was evacuated through a diaphragmatic rent identified during the surgery. This illustrates the catastrophic complications of an amoebic liver abscess.

Is there a need to be worried about the new monkeypox virus outbreak? A brief review on the monkeypox outbreak.

The Monkeypox virus (MPXV) is a double-stranded DNA virus related to the orthopoxvirus genus in the family of poxviridae. MPXV is endemic in central and Western African countries. There have been several outbreaks of MPXV in non-endemic countries since it was discovered in 1958 in lab monkeys. The current spread of MPXV is different from previous outbreaks, raising concerns about its potential to cause pandemics around the world. In order to reduce the spread of the disease, several countries imposed different preventive measures. The MPXV virus is believed to be transmitted either through wild animals, such as rodents or through infected individuals. Every year, Africa experiences a few thousand cases, mostly in the west and central regions. The number of cases outside Africa has previously been limited to a handful associated with travel to Africa or with the importation of infected animals. In this narrative review, we will discuss the clinical diagnosis, transmission, distribution, treatment, and prevention of the recent monkeypox outbreak around the world.

Central positional vertigo as first initial multiple sclerosis symptom: A case report with systematic review.

Multiple sclerosis is a disease that affects the central nervous system, resulting in various symptoms such as vision, physical activity, and stability. Central positional vertigo as initial multiple sclerosis symptoms are a rare case. It increases the attention of doctors to follow accurate measurements to diagnose multi sclerosis regarding the initial symptoms.

Subdural empyema due to mixed infections successfully treated medically: A case report with review literature.

Subdural empyema is a rare intracranial infection with an accumulation of purulent material between the dura and arachnoid matter. We report a case of 17 years old presented with an altered conscious level. CSF analysis showed increased WBCs. His situation has improved after treating by acyclovir, ceftriaxone, vancomycin, and dexamethasone.