Safety and efficacy of Magnesium Sulfate in the management of Tetanus: A systematic review.

Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.

Neurological manifestations of COVID-19: a systematic review.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our understanding of the impact this virus has on the nervous system is limited. Our review aims to inform and improve decision-making among the physicians treating COVID-19 by presenting a systematic analysis of the neurological manifestations experienced within these patients. METHODS: Any study, released prior to May 20, 2020, that reported neurological manifestations in patients infected by SARS-CoV-2 was systematically reviewed using the PRISMA (Preferred Reporting Items for Systemic review and Meta-Analysis) statement. RESULTS: Our systematic review included data from 37 articles: twelve retrospective studies, two prospective studies, and the rest case reports/series. The most commonly reported neurological manifestations of COVID-19 were myalgia, headache, altered sensorium, hyposmia, and hypogeusia. Uncommonly, COVID-19 can also present with central nervous system manifestations such as ischemic stroke, intracerebral hemorrhage, encephalo-myelitis, and acute myelitis, peripheral nervous manifestations such as Guillain-Barré syndrome and Bell's palsy, and skeletal muscle manifestations such as rhabdomyolysis. CONCLUSION: While COVID-19 typically presents as a self-limiting respiratory disease, it has been reported in up to 20% of patients to progress to severe illness with multi-organ involvement. The neurological manifestations of COVID-19 are not uncommon, but our study found most resolve with treatment of the underlying infection. Although the timeliness of this review engages current challenges posed by the COVID-19 pandemic, readers must not ignore the limitations and biases intrinsic to an early investigation.

Efficacy and safety of inhaled budesonide on prevention of acute mountain sickness during emergent ascent: a meta-analysis of randomized controlled trials.

BACKGROUND: Acute Mountain Sickness (AMS) is a pathophysiologic process that occurs in non-acclimated susceptible individuals rapidly ascending to high-altitude. Barometric pressure falls at high altitude and it translates to a decreased partial pressure of alveolar oxygen (PAO2) and arterial oxygen (PaO2). A gradual staged ascent with sufficient acclimatization can prevent AMS but emergent circumstances requiring exposure to rapid atmospheric pressure changes - such as for climbers, disaster or rescue team procedures, and military operations - establishes a need for effective prophylactic medications. This systematic review and meta-analysis aim to analyze the incidence of AMS during emergent ascent of non-acclimatized individuals receiving inhaled budesonide compared to placebo. METHODS: This current meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched PubMed, Google Scholar and Embase for relevant studies. The efficacy of budesonide in reducing incidence of AMS was evaluated by calculating the pooled ORs and 95% CIs. The efficacy of budesonide in maintaining hemoglobin-oxygen saturation was evaluated by calculating standard mean difference (SMD) and 95% confidence intervals. RESULTS: We found that at high altitude, inhaled budesonide was effective in reducing the incidence of mild AMS [OR: 0.37; 95% CI, 0.14 to 0.9, p = 0.042] but was ineffective in reducing the incidence of severe AMS [OR: 0.46; 95% CI, 0.14 to 1.41, p = 0.17]. Inhaled budesonide was also effective in maintaining SpO2 (SMD: 0.47; 95% CI, 0.09 to 0.84, p = 0.014) at high altitude. However, it was not effective in maintaining or improving pulmonary function at high altitude. Systematic-review found no adverse effects of budesoide in the dose used for prophylaxis of AMS. CONCLUSIONS: Our systematic review showed that prophylactic inhaled budesonide is effective in preventing mild AMS during emergency ascent but not effective in preventing severe AMS. Though statistically significant, authors recommend caution in interpretation of data and questions for further well designed randomized studies to evaluate the role of budesonide in prophylaxis of AMS during an emergent ascent.

Status of prehospital delay and intravenous thrombolysis in the management of acute ischemic stroke in Nepal.

BACKGROUND: Intravenous thrombolysis has been recently introduced in Nepal for the management of acute ischemic stroke. Pre-hospital delay is one of the main reasons that hinder thrombolytic therapy. The objective of this study was to evaluate the status of prehospital delay and thrombolysis in Nepal. METHODS: Data were prospectively collected from patients of both genders, age >  18 years who arrived at the emergency department (ED) with symptoms and neuroimaging findings consistent with an ischemic stroke. Patient data were obtained from ED form and standard questionnaires were used to assess factors resulting in prehospital delay. Modified Rankin scale and National Institute of Health stroke scale were used to assess the degree of disability and severity of stroke respectively. RESULTS: A total of 228 patients were enrolled in the study between August 2017 and August 2018. Only 46 (20.17%) patients arrived within the time frame for thrombolysis. Onset at daytime (OR: 4.07; 95% CI: 1.65-10.1; p = 0.001), stroke symptoms facial deviation (OR: 5.03; 95% CI: 2.47 to 10.26; p = 0.000) and speech disturbances (OR: 2.34; 95% CI: 1.06 to 5.1; p = 0.021), identification of stroke (OR: 22.36; 95% CI: 9.42-53.04;p = 0.000), rushing to ED after onset of symptoms (OR: 2.93; 95% CI: 1.5-5.7; p = 0.001), awareness of treatment of stroke (OR: 10.21; 95% CI: 4.8-21.6; p = 0.000), direct presentation (OR: 4.2; 95% CI: 2.09-8.66; p = 0.000), the distance less than 20 km (OR: 7.9; 95% CI: 3.8-16.5; p = 0.000), and education above high school (OR:4.85; 95% CI: 2.2-10.5; p = 0.000) were associated with early arrival. Heavy traffic, income below 1000 USD per annum and diabetes mellitus were associated with delayed arrival to ED. Out of 46 early arrival patients, only 30 patients (13.15%) received tissue plasminogen activator during the study period, while others were deprived because of their inability to afford the treatment cost. CONCLUSION: Community-based intervention to spread awareness, establishing comprehensive stroke centers, training specialists, improving emergency services, establishment of telestroke facilities and encouraging the use of low-cost tenecteplase as an alternative to alteplase can help improve care for stroke patients in Nepal.

A case report of triple neural tube defect: revisiting the multisite closure theory.

BACKGROUND: Triple neural tube defects are rare. To the author's knowledge, there are only four reported cases available in the literature up to date. Controversies exist with regards to the development of neural tube defects. We revisit the multisite closure theory and try to explain the mechanism of neural tube defects in our case. CASE PRESENTATION: We report a case of one-month-old baby boy who presented to us with three distinct neural tube defects. He had occipital and cervical encephaloceles along with thoracolumbar myelomeningocele accompanied by syrinx and mild hydrocephalus. All the three defects were surgically corrected with good neurological outcome. CONCLUSION: In the multisite model of human neural tube closure, there are only two fusion sites and two neuropores unlike in mouse. This can explain the origin of open neural tube defects including anencephaly and myelomeningocele (as in our case) but cannot account for the development of encephalocele, which appears to be a post neurulation defect.

Delayed-Onset High Altitude Pulmonary Edema: A Case Report.

High altitude pulmonary edema (HAPE) is a life-threatening altitude illness that usually occurs in insufficiently acclimatized climbers in the first few days at altitudes above 2500 m. Acetazolamide is recommended for prophylaxis of acute mountain sickness, but a role for acetazolamide in the prevention of HAPE has not been established. We report a case of a trekker with previous high altitude experience who developed HAPE 8 d after arrival to altitude despite what was believed to be a conservative ascent profile.

Utilization rates of intravenous thrombolysis for acute ischemic stroke in Asian countries:: A systematic review and meta-analysis.

BACKGROUND: Despite intravenous thrombolysis (IVT) being used for the treatment of acute ischemic stroke (AIS) for over two decades, its accessibility remains limited in various regions of the world. The Asian region, which experiences the highest age-standardized incidence of AIS, currently lacks comprehensive data on the utilization of IVT. AIMS: This study aimed to provide precise estimates of IVT usage for AIS in Asian countries. METHODS: A literature search was conducted on PubMed and Google using appropriate search terms. English language, peer reviewed articles published after 2010 were included in the analysis. The pooled proportion was calculated utilizing the DerSimonian and Laird random-effects model. Additionally, a subgroup analysis was conducted, taking into account factors such as the study's country, the economic status of the country, specific Asian regions, publication year (before 2015 and from 2015 onwards), study location, study setting, hospital stroke protocol, and national stroke guidelines. RESULTS: 67 observational studies with 778,046 patients with AIS were included in the meta-analysis. The overall utilization rate of IVT was found to be 9.1%. High-income countries had a higher rate (11.3%) compared to lower-middle-income (8.1%) and upper-middle-income countries (9%). Central and North Asia had the highest rate (17.5%) and Southeast Asia had the lowest rate (6.8%). Studies conducted after 2015 had a higher thrombolysis rate (11.3%) compared to those before 2015 (1.5%). Presence of hospital stroke protocols (10.7%) and national stroke guidelines (10.1%) were associated with higher thrombolysis rates. CONCLUSION: The overall utilization rate of IVT for AIS in Asia stood at 9.1%, showcasing noteworthy disparities across countries, regions, and income brackets. To improve thrombolysis rates in the region, addressing prehospital delays, increasing public awareness, and implementing stroke protocols and national guidelines are key strategies.

Bilateral thalamic infarction following cerebral venous thrombosis in a patient with ulcerative colitis.

Cerebral Venous Thrombosis is a rare extra-intestinal manifestation of ulcerative colitis. Ulcerative colitis is a hypercoagulable state and, if poorly managed, can predispose to thrombosis, including thrombosis of the cerebral veins.

Salivary alpha-synuclein as a potential fluid biomarker in Parkinson's disease: A systematic review and meta-analysis.

Introduction: Lewy bodies are the pathological hallmarks of Parkinson's disease. There is a need for effective biomarker that is cost effective, less invasive, and easily reproducible with good sensitivity and specificity and can be used to diagnose the condition early and track its severity and progression. Alpha-synuclein (α-syn), an integral component of the Lewy body, is found in saliva and can be a potential answer to the above concerns. Methods: PubMed, EMBASE, Google Scholar, and CNKI databases, along with additional sites, were searched from January 2010 to August 2021. Standard mean difference (Hedges' g) with 95% CI was used to show an association. Statistical analysis was done using STATA software version 16 (StataCorp). Results: We found a significant reduction in the mean difference of total salivary α-syn among PD patients compared to healthy controls. However, the mean difference of oligomeric α-syn and oligo/total salivary α-syn ratio was significantly increased among PD patients compared to healthy controls. Conclusion: Our systematic review and meta-analysis found that salivary α-syn parameters (total, oligomeric, oligo/total) can be considered a simple, easy-to-use, cost-effective, and reliable diagnostic biomarker for PD and its progression.

Safety and efficacy of low-cost alternative urokinase in acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS. METHODS: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021. RESULTS: A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I2 = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I2 = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I2 = 0 %; P = 0.30). CONCLUSION: Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.

Cerebral venous thrombosis in a patient with adenomyosis: A case report.

Cerebral venous thrombosis can be caused by different conditions such as infectious, structural, hypercoagulable states, hematological, hormonal, collagen, vascular diseases, and oral contraceptive pills among other causes. Adenomyosis has been rarely associated with Cerebral venous thrombosis (CVT). Increased CA-125 and iron deficiency anemia in adenomyosis may predispose to CVT.

Therapeutic drug level of tacrolimus causing intracranial hemorrhage in a patient with renal transplant.

Tacrolimus is used in solid organ transplant patients to prevent rejection, and no case of intracerebral hemorrhage (ICH) has been reported till date. We report a case of 31-year-old man with diabetes and hypertension for ten years who had a renal transplant four years back; diagnosed with tacrolimus-induced ICH.

Safety and efficacy of intravenous thrombolysis in acute ischemic stroke patients with a history of intracranial hemorrhage: A systematic review and meta-analysis.

Acute ischemic stroke (AIS) is a fatal and debilitating condition killing 2.7 million people each year worldwide. The most commonly used treatment modality for AIS is intravenous thrombolysis (IVT) with alteplase which is indicated for those presenting within 4.5 h of onset. Due to a lack of reliable evidence on harm or benefit, the 2019 American Heart Association/American Stroke Association (AHA/ASA) guidelines consider a history of previous intracranial hemorrhage (ICH) as potentially harmful and no longer an absolute contraindication for IVT in patients with AIS, and the U.S. Food and Drug Administration (FDA) removed chronic ICH as a specific contraindication for IVT from the label in 2015. Despite a shift in guidelines, physicians frequently face the dilemmatic choice whether to administer IVT in this subset of patients due to the risk of symptomatic intracranial hemorrhage (SICH). The benefit of IVT in such patients has not been thoroughly investigated, and there are only a few studies on the subject in the literature to date. We conducted the present meta-analysis in an aim to provide solid evidence on the efficacy and safety of IVT for treating AIS in patients with a history of remote ICH. Our meta-analysis found that IVT improves functional outcomes in AIS patients with prior remote ICH without increasing SICH or all-cause mortality. These findings may contribute to the decision-making process for IVT administration in AIS patients.

Cervical vagal schwannoma, a rare differential of a neck swelling: A case report.

Cervical vagal schwannoma is a rare clinical entity that requires a different clinical approach than other neck swellings. Magnetic resonance imaging is the preferred initial diagnostic test. Complications may arise due to vagal stimulation in unsuspecting open biopsies. Surgical excision with perioperative vagal monitoring is recommended for the treatment of vagal schwannomas.

Amyotrophic lateral sclerosis and retinal changes in optical coherence tomography: A systematic review and meta-analysis.

INTRODUCTION: Increasing evidence suggests Amyotrophic Lateral Sclerosis (ALS) as a widespread pathological process comprising nonmotor features like fatigue, mild sensory symptoms, cognitive decline, and visual impairment. Measurements of retinal nerve fiber layer (RNFL) thickness using Optical Coherence Tomography (OCT) may correlate with the neurodegeneration associated with ALS. In addition to RNFL thickness, other OCT parameters have been explored in the context of diagnosing ALS and predicting disease severity. In this study, we explore the possibility that OCT parameters of patients with ALS may differ significantly from those of healthy controls and thus serve as biomarkers for the disease and its progression. MATERIALS AND METHODS: Between 2010 and 2021, the PubMed and EMBASE databases were examined for English language literature. ALS severity was assessed using the revised ALS functional rating scale (ALSFRS-R). The pooled mean differences in RNFL thickness between ALS patients and controls were calculated using the Standard Mean Difference (Hedges's g) with a 95% confidence interval (CI) in STATA software version 16. RESULTS: Eleven studies were reviewed for data collection. RNFL thickness was not statistically significantly different between ALS patients (n = 412) and controls (n = 376) (Hedges's g = -0.22; 95% CI: -0.51 to 0.07, I2 = 73.04%, p = .14). However, the thickness of inner nuclear layer was significantly different between ALS patients and controls (Hedges's g = -0.38; 95% CI: -0.61 to 0.14, I2 = 14.85%, p = .00). CONCLUSION: Our meta-analysis found that RNFL thickness as a whole or by individual quadrants was not significantly different between ALS patients and controls while the inner nuclear layer (INL) was substantially thinner.

An opportunity to improve Acute Ischemic Stroke care in the South Asian region through telestroke services.

The South Asian region accounts for more than 40% of the stroke burden of the developing world and is the highest contributor to global stroke mortality. Despite proven treatment guidelines, the limited number of neurologists, the number of dedicated stroke centers and the fact that most of these facilities are urban-centric renders poor access to thrombolysis in this region, especially in the rural areas. Studies have shown that thrombolysis using telestroke services are comparable to face-to-face thrombolysis. Telestroke, conducted through low-cost media such as smartphones or laptops, may form a cost-effective solution to improve access to appropriate stroke care in a resource-limited setting such as that of the South Asian region.

Role of female community health volunteers in ischemic stroke prevention, identification, referral and rehabilitation in Nepal.

For the past three decades, female community health volunteers (FCHVs) have been at the forefront of Nepal's health map and have contributed significantly to its improving health indicators such as maternal mortality rate and infant mortality rate. Given the changing epidemiology of Nepal and the shift of burden from communicable to non-communicable diseases (NCDs), it is important to revitalize their role with the changing times. The prevalence of ischemic stroke in Nepal is on the rise. However, very few people make it to the hospital within the time frame for thrombolysis and the patient's knowledge about ischemic stroke seems to play a major part. FCHVs can play a significant role in improving ischemic stroke care by raising awareness about the condition, its risk factors, and informing the public about the need for timely treatment. They can help screen for common risk factors such as obesity, hypertension and diabetes as well as monitor for treatment in previously diagnosed individuals. Randomized controlled trials have shown to yield favorable results in NCDs with engagement of FCHVs. With proper training and support, they can play an important role in improving ischemic stroke care in low- and middle-income countries like Nepal.

Low-cost alternatives for the management of acute ischemic stroke in low and middle-income countries.

Acute ischemic stroke (AIS) patients arriving within a suitable time frame are treated with recanalization therapy i.e. intravenous thrombolysis (IVT) with alteplase and/or mechanical thrombectomy (MT). IVT with alteplase is indicated in AIS patients presenting within 4.5 hours of onset regardless of vascular territory involved. MT is indicated in AIS patients presenting within 24 hours of onset with large vessel occlusion in the anterior circulation. However, MT is ludicrously expensive and requires exorbitant setup, devices, and expertise which is not currently feasible in LMICs. Therefore, in LMICs the only feasible recanalization option left for AIS patients is IVT. The cost of IVT varies across the LMICs, however, most of them cost around 2000-5000 USD. Apart from IVT, patients with AIS often have other significant medical costs including those for neuroimaging, intensive care, and prolonged rehabilitative treatment. In LMICs, these costs can only be afforded by a handful of patients. The majority of the LMICs have health insurance in their infancy and family members of AIS patients opt-out IVT due to the economic burden. In general, the current treatment guidelines for AIS are not very useful in LMICs because of cost-related issues among several other factors. In this editorial, we discuss evidence for alternative treatment strategies that can help tackle the rising epidemic of AIS in poor countries by improvising on existing clinical guidelines and seeking alternative treatment regimens.

The dangers of mass drug administration of albendazole in Nepal, a Neurocysticercosis-endemic region.

The majority of cases of Neurocysticercosis (NCC) are asymptomatic. Injudicious use of antihelmintics like albendazole (ALB) can cause cyst degeneration and perilesional inflammation, thus rendering asymptomatic individuals symptomatic with seizures, headache, vascular events, or cerebral edema. Mass drug administration (MDA) using ALB is a very common practice in developing countries like Nepal to contain transmission of soil-transmitted helminths (STH) and lymphatic filariasis (LF). Although the benefits of ALB-based MDA in the general population cannot be undermined, there can be severe consequences in certain groups, especially those with latent NCC. In this commentary, we discuss the effect it may have on such patients, and suggest potential solutions.

Association between K469E polymorphism of ICAM-1 gene and susceptibility of ischemic stroke: An updated meta-analysis.

BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1)/leukocyte function associated antigen-1 (LFA-1) adhesion system regulates leukocyte interactions, migration, and adhesion, and appears to play an important role in atherosclerosis and thrombosis. Therefore, single nucleotide polymorphisms (SNPs) of the ICAM-1 gene may strongly influence the expression and biological activity of ICAM-1 and play a potentially important role in the pathogenesis of ischemic stroke. In the current meta-analysis, we investigated the relationship between the ICAM-1 gene K469E SNP and the risk of ischemic stroke. METHODS: Two investigators independently searched PubMed, Web of Science, Google Scholar, WANFANG, China National Knowledge Infrastructure (CNKI) and J-STAGE for studies published from January 2000 to February 2019 without language restriction. The association of K469E polymorphism and ischemic stroke in three genetic models (allelic, recessive, and dominant) were evaluated using Pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Our study included 20 studies from four continents and four different countries, including 3,137 cases and 15,382 controls. Meta-analysis results did not show a significant association between K469E polymorphism of ICAM-1 gene and ischemic stroke when assuming allelic model (OR: 1.12; 95% CI: 0.8 to 1.55; p = 0.51; I2  = 93%) or recessive model (OR: 1.28; 95% CI: 0.89 to 1.84; p = 0.18; I2  = 82%) or dominant model (OR: 1.20; 95% CI: 0.92 to 1.56; p = 0.17; I2  = 85%). However, in all three genetic models, subgroup analysis revealed that the K469E polymorphism of the ICAM-1 gene is associated with ischemic stroke in the Caucasian population. CONCLUSION: K469E polymorphism of ICAM-1 gene might be a risk factor for ischemic stroke in Caucasians, which suggested that K469E polymorphism might help in early identification of those at risk and help in primary prevention of ischemic stroke.