Developing Systems of Emergency and Inpatient Neurologic Care in Resource-Limited Settings.

Neurologic diseases represent a significant global health challenge, leading to disability and mortality worldwide. Healthcare systems in low- and middle-income countries are disproportionally affected. In these resource-limited settings, numerous barriers hinder the effective delivery of emergency and inpatient neurologic care, including shortages of trained personnel, limited access to diagnostics and essential medications, inadequate facilities, and absence of rehabilitation services. Disparities in the neurology workforce, limited access to neuroimaging, and availability of acute interventions further exacerbate the problem. This article explores strategies to enhance global capacity for inpatient neurologic care, emphasizing the importance of workforce development, context-specific protocols, telehealth solutions, advocacy efforts, and collaborations.

Neurological manifestations and complications of COVID-19 in patients admitted to a tertiary care center in Nepal during the second wave.

Neurological symptoms and signs of Coronavirus disease-19 (COVID-19) can accompany, follow, or precede respiratory symptoms and signs; hence, they are important in the diagnosis and management of COVID-19 patients. In this retrospective study conducted during the second wave of COVID-19, we included all patients diagnosed with COVID-19 using real-time polymerase chain reaction and admitted to the Tribhuvan University Teaching Hospital between June 2021 and October 2021. The patients were categorized into 2 groups: group A (with neurological manifestations or complications) and Group-B (without neurological manifestations or complications). The 2 groups were compared in terms of intensive care unit (ICU) admission, need for ventilatory support, length of hospital stay, and various outcomes. The study included 235 participants ranging in age from 13 to 102 years (mean age = 54 years, standard deviation = 18). Among the participants, 54.50% were male. The proportion of individuals in group A was higher (59.15%, N = 139) than that in Group-B (40.85%, N = 96). Notably, a significantly greater number of patients were admitted to the ICU in Group B than in Group A. However, there were no statistically significant differences in the need for ventilatory support or hospital stay between the 2 groups. Interestingly, group A showed a higher rate of improvement (Z = -3.1145, P = .00188, 95% CI), while Group-B had a higher rate of mortality (Z = 4.5562, P < .00001, 95% CI). Altered mental status and stroke have been specifically linked to poorer outcomes, whereas typical neurological manifestations, such as hyposmia, hypogeusia, dizziness, headache, and myalgia, are associated with better outcomes.

Neurological and neuro-ophthalmological manifestations of snake bite: a systematic review.

Objective: Snakebites, a major health concern in developing countries, affect rural farming communities. Venom, primarily neurotoxin, injected during a snake bite disrupts the nervous system, causing symptoms like muscle weakness, paralysis, altered sensation, and coordination issues. This review focuses on evaluating neurological and neuro-ophthalmological manifestations associated with snakebites. Methods: A database search was conducted in EMBASE and PubMed for studies published from 2000 to 2023. The investigation centered on examining neurological and neuro-ophthalmological symptoms and signs, treatment approaches, treatment outcomes, and long-term complications of snake bites. Results: Neurological and neuro-ophthalmological symptoms were common in both neurotoxic and hemotoxic snake bites, especially in neurotoxic cases. Ptosis was a prevalent manifestation across various snake bites, along with respiratory paralysis, limb weakness, dysphasia, and visual disturbances in some instances. However, most patients improved without residual neurological symptoms after treatment. Conclusions: Understanding patterns of neurological manifestations contributes valuable insights for the comprehensive management of snakebite.

MicroRNA Expression Profile in Acute Ischemic Stroke.

Introduction: Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors such as inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels. In this context, microRNAs (miRNAs) have emerged as a promising biomarker, demonstrating potential as biomarkers across various diseases, including cancer, cardiovascular conditions, and neurological disorders. These circulating miRNAs embody a wide spectrum of pathophysiological processes, encompassing cell death, inflammation, angiogenesis, neuroprotection, brain plasticity, and blood-brain barrier integrity. This pilot study explores the utility of circulating exosome-enriched extracellular vesicle (EV) miRNAs as potential biomarkers for anterior circulation LVO (acLVO) stroke. Methods: In our longitudinal prospective cohort study, we collected data from acute large vessel occlusion (acLVO) stroke patients at four critical time intervals post-symptom onset: 0-6 hours, 6-12 hours, 12-24 hours, and 5-7 days. For comparative analysis, healthy individuals were included as control subjects. In this study, extracellular vesicles (EVs) were isolated from the plasma of participants, and the miRNAs within these EVs were profiled utilizing the NanoString nCounter system. Complementing this, a scoping review was conducted to examine the roles of specific miRNAs such as miR-140-5p, miR-210-3p, and miR-7-5p in acute ischemic stroke (AIS). This review involved a targeted PubMed search to assess their influence on crucial pathophysiological pathways in AIS, and their potential applications in diagnosis, treatment, and prognosis. The review also included an assessment of additional miRNAs linked to stroke. Results: Within the first 6 hours of symptom onset, three specific miRNAs (miR-7-5p, miR-140-5p, and miR-210-3p) exhibited significant differential expression compared to other time points and healthy controls. These miRNAs have previously been associated with neuroprotection, cellular stress responses, and tissue damage, suggesting their potential as early markers of acute ischemic stroke. Conclusion: This study highlights the potential of circulating miRNAs as blood-based biomarkers for hyperacute acLVO ischemic stroke. However, further validation in a larger, risk-matched cohort is required. Additionally, investigations are needed to assess the prognostic relevance of these miRNAs by linking their expression profiles with radiological and functional outcomes.

Critical care delivery across health care systems in low-income and low-middle-income country settings: A systematic review.

Background: Prior research has demonstrated that low- and low-middle-income countries (LLMICs) bear a higher burden of critical illness and have a higher rate of mortality from critical illness than high-income countries (HICs). There is a pressing need for improved critical care delivery in LLMICs to reduce this inequity. This systematic review aimed to characterise the range of critical care interventions and services delivered within LLMIC health care systems as reported in the literature. Methods: A search strategy using terms related to critical care in LLMICs was implemented in multiple databases. We included English language articles with human subjects describing at least one critical care intervention or service in an LLMIC setting published between 1 January 2008 and 1 January 2020. Results: A total of 1620 studies met the inclusion criteria. Among the included studies, 45% of studies reported on pediatric patients, 43% on adults, 23% on infants, 8.9% on geriatric patients and 4.2% on maternal patients. Most of the care described (94%) was delivered in-hospital, with the remainder (6.2%) taking place in out-of-hospital care settings. Overall, 49% of critical care described was delivered outside of a designated intensive care unit. Specialist physicians delivered critical care in 60% of the included studies. Additional critical care was delivered by general physicians (40%), as well as specialist physician trainees (22%), pharmacists (16%), advanced nursing or midlevel practitioners (8.9%), ambulance providers (3.3%) and respiratory therapists (3.1%). Conclusions: This review represents a comprehensive synthesis of critical care delivery in LLMIC settings. Approximately 50% of critical care interventions and services were delivered outside of a designated intensive care unit. Specialist physicians were the most common health care professionals involved in care delivery in the included studies, however generalist physicians were commonly reported to provide critical care interventions and services. This study additionally characterised the quality of the published evidence guiding critical care practice in LLMICs, demonstrating a paucity of interventional and cost-effectiveness studies. Future research is needed to understand better how to optimise critical care interventions, services, care delivery and costs in these settings. Registration: PROSPERO CRD42019146802.

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.

Post-COVID-19 acute disseminated encephalomyelitis in a 51-year-old female from Nepal: A case report with literature review.

There have been a growing number of acute disseminated encephalomyelitis cases following coronavirus disease-19 (COVID-19) infection. Given the rare occurrence, studies eliciting the clinical features, treatment response, and outcomes are still limited. In patients recovering from COVID-19, multifocal neurologic symptoms in the presence or absence of encephalopathy must be closely evaluated by neurologists and physicians. Early radiographic evaluation using magnetic resonance imaging and timely administration of glucocorticoid-based treatment reduces mortality and leads to satisfactory outcomes.

An institutional experience of hydatidosis and cysticercosis in Nepal: a retrospective chart review.

This study aimed to investigate the demographic characteristics, anatomical distribution, and histopathological features of hydatidosis and cysticercosis in a Nepalese population presenting to a tertiary care hospital. The study also aimed to provide a better understanding of the clinical and pathological aspects of these diseases in the local context. Methods: This retrospective study analyzed all cases of hydatidosis and cysticercosis reported in the Department of Pathology at Tribhuvan University Teaching Hospital between January 2013 and December 2019. Demographic, clinical, radiological, and histopathological data were collected and analyzed from hospital charts. Results: During the 7-year study period, the authors identified 112 cases of hydatid cysts and 26 cases of cysticercosis. The mean age of patients with hydatidosis was 33.86 years (range: 5-74 years), while the mean age of patients with cysticercosis was 25.39 years (range: 4-63 years). Females were more commonly affected with hydatidosis (68, 61.7%) than males (44, 39.3%), resulting in a male-to-female ratio of 0.6:1. In contrast, there was no significant sex difference in cysticercosis cases, with 14 (53.85%) males and 12 (46.15%) females affected. The most commonly affected site for hydatid cysts was the lung (47 cases, 42%), followed by the liver (41 cases, 36.6%). The study identified three cases of neurocysticercosis. The average diameter of hydatid cysts and cysticercosis was 8.7 cm and 1.7 cm, respectively. Conclusion: In conclusion, our study provides important insights into the clinical and pathological features of hydatidosis and cysticercosis in a Nepalese population. These zoonotic diseases pose a significant health burden, particularly among the poor and marginalized populations. Our findings highlight the need to integrate prevention and control measures into the healthcare system to decrease the overall burden of these diseases.

Schizencephaly diagnosed after an episode of seizure during labor: A case report.

Schizencephaly, an extremely rare anomaly of the cortex, is characterized by abnormal clefts in the cerebral cortex. Very often, this condition is diagnosed early in the childhood period but few instances exist in literature where schizencephaly-associated seizures and hemiparesis have presented later in life too. Here, we report a rare case scenario of a lady in her late 30s who initially presented to us with obstetric concerns wherein schizencephaly remained an incidental finding despite the significantly large cortical cleft along with lobar holoprosencephaly and lissencephaly.

Multicentre registration of wake-up stroke in China (MCRWUSC): a protocol for a prospective, multicentre, registry-based cohort study.

INTRODUCTION: Wake-up stroke (WUS) is a type of acute ischaemic stroke (AIS) that occurs during sleep with unknown time of symptom onset. The best treatment is usually not suitable for WUS, as thrombolysis is usually provided to patients who had a symptomatic AIS within a definite 4.5 hours, and WUS remains a therapeutic quandary. Efforts to explore the onset time characteristics of patients who had a WUS and the risk factors affecting poor prognosis support a role for providing new insights by performing multicentre cohort study. METHODS AND ANALYSIS: This multicentre, nationwide prospective registry will include 21 comprehensive stroke centres, with a goal of recruiting 550 patients who had a WUS in China. In this study, clinical data including patient's clinical characteristics, stroke onset time, imaging findings, therapeutic interventions and prognosis (the National Institutes of Health Stroke Scale Score and the modified Rankin Scale Score at different time points) will be used to develop prediction models for stroke onset time and prognostic evaluation using the fast-processing of ischemic stroke software. The purpose of this study is to identify risk factors influencing prognosis, to investigate the relationship between the time when the symptoms are found and the actual onset time and to establish an artificial intelligence-based model to predict the prognosis of patients who had a WUS. ETHICS AND DISSEMINATION: This study is approved by the ethics committee of Shanghai Pudong Hospital (Shanghai, China) and rest of all participating centres. The findings will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: ChiCTR2100049133.

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.

Safety and efficacy of endovascular thrombectomy in patients with severe cerebral venous thrombosis: A meta-analysis.

Background: Cerebral venous thrombosis (CVT) is a rare thrombotic condition which is traditionally treated with anti-coagulation therapy. Subsets of patients with severe CVT have been treated with endovascular thrombectomy (EVT). Despite the high estimated mortality associated with severe CVT, there has been only one randomized control trial done regarding safety and efficacy of EVT in severe CVT compared to standard medical management. Evidence in this area is lacking. Objective: The aim of this systematic review is to analyze all existing literature and generate robust information regarding the role of EVT in the management of patients with severe CVT. Methods: This systematic review and meta-analysis followed PRISMA guideline. PubMed, Embase, Google Scholar, and CNKI were searched for eligible studies from 2007 to 2021. Safety and efficacy of EVT were evaluated by meta-analyzing recanalization status, the good functional outcome at follow-up, recurrent CVT, new hematoma. A pooled proportion with a 95% confidence interval was derived from a meta-analysis of various outcomes (CI). Results: A total of 33 studies comprising 610 patients treated with EVT were included for analysis which comprised one randomized control trial, one prospective study and 31 retrospective studies. Based on pooled data, 85% of patients had good functional outcome, 62% had complete recanalization, 5% had all-cause mortality, and 3% had catheter related complications. The efficacy outcomes in this analysis had a significant heterogeneity and a subgroup analysis was also done to explain these findings. The minimum time of follow up was 3 months and varied EVT techniques were used across the studies. Conclusion: This meta-analysis suggests EVT may be safe and efficacious in treating patients with severe CVT. Registration: Our protocol was registered with PROSPERO: International prospective register of systematic reviews with the registration number CRD42021254760.

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.

Low-dose alteplase for the management of acute ischemic stroke in South Asians: A systematic review on cost, efficacy and safety.

INTRODUCTION: South Asia is responsible for more than 40% of the stroke burden and stroke mortality in the developing world. South Asia, which is home to one-fourth of the world's population, is the most densely populated and one of the poorest regions. The majority of patients in this region are unable to afford intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). If low-dose alteplase proves effective and safe in South Asians, it may be a more cost-effective treatment option. METHODS: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Researchers searched PubMed, EMBASE, and Google Scholar for English literature from 2005 to 2021. END, ENI, good functional outcome, SICH, and all-cause mortality were used to assess efficacy and safety. RESULTS: In the low-dose alteplase treated patients, different studies reported 32 to 57% ENI 24 h after IVT, and 7% to 9.7% END. At 3 months follow-up, good functional outcome was achieved by 48%-76.92% of low-dose alteplase treated patients. SICH rates ranged from 0% to 16.6% across studies. Asymptomatic ICH occurred in 5-14% of patients. The mortality rate in all included studies varied from none to 25%. CONCLUSION: Our systematic review demonstrates that the use of low-dose alteplase for AIS in the South Asians offer comparable efficacy and reduced risk of SICH at a significantly lower cost than standard alteplase dose. Future well-randomized clinical trials are necessary to validate the findings of our study.

Bell's palsy as a possible complication of mRNA-1273 (Moderna) vaccine against COVID-19.

Introduction: Vero Cell, AstraZeneca, Janssen, mRNA-1273 (Moderna), and Pfizer COVID-19 vaccines have been authorized for emergency use in Nepal. These vacines have been linked to some adverse effects, including fever, myalgia, and headache. Furthermore Bell's Palsy a rare adverse effect was also reported to be associated with the use of mRNA-1273 (Moderna) vaccine in some patients. Case presentation: In this case report we present a 17-year-old female who acquired Bell's Palsy following the administration of mRNA-1273 (Moderna) COVID-19 vaccination. Discussion: The possible etiology of BP that has been suggested is infection by reactivated viruses, such as the varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), human herpesvirus 6, and the Usutu virus, [1] the most accepted hypothesis is the one with reactivation of latent Herpes Simplex Virus type 1 in the geniculate ganglia of the facial nerves, an autoimmune mechanism through the mimicry of host molecules by the antigens of the vaccines. Conclusion: Though the extent of association between the mRNA vaccination and the development of Bell's Palsy has yet to be confirmed, this example highlights the need to closely monitor side effects and repercussions after receiving a new vaccine.

Klippel-Trenaunay Syndrome: Case series from a university hospital of Nepal.

Introduction: Klippel Trenaunay Syndrome (KTS) is a rare congenital malformation with capillary and venous malformations and soft tissue/bony overgrowth with or without lymphatic malformation. Cutaneous vascular stain, varicosities and tissue hypertrophy represent its main clinical features. Besides, the patient can develop thromboembolic pathologies, recurrent bouts of infection, stasis eczema, limb length discrepancy and intolerable pain typical of intraosseous involvement. Methods: Here, we report a case series of seven patients aged 10-45 who presented to our centre with clinical features suggestive of KTS. Out of them, six patients had involvement of unilateral lower limb, while only one had involvement of bilateral lower limb. They all had typical cutaneous vascular stains and underlying venous malformation, while one patient had developed complications with multiple ulcer formation. Outcomes: An interdisciplinary team of vascular surgeons, dermatologists, interventional radiologists, orthopaedics, and physiotherapists managed the cases. We performed an individualized treatment as per the patient's presentation, which included a combination of supportive, medical, interventional radiologic, and surgical interventions. The follow-up outcomes of all the patients revealed significant resolution of symptoms. Conclusion: Patients with KTS can have diverse presentations. Therefore, clinicians should ensure an individualized treatment with the involvement of a multidisciplinary team for proper management and prevention of complications.

Guillain-Barré syndrome after mRNA-1273 (Moderna) COVID-19 vaccination: A case report.

Guillain-Barre syndrome (GBS) is an acquired inflammatory polyradiculoneuropathy that often follows infection with a virus or bacteria and in rare occasions, vaccination may precede GBS. We present a case of 80-year-old male patient who presented with chief complaints of progressive, ascending bilateral lower extremity paresthesia and weakness following first dose of Moderna vaccine. His symptoms got exacerbated after 2nd dose. Clinical examination and investigation findings including lumbar puncture, nerve conduction study, and electromyography were consistent with the diagnosis of GBS. The patient received treatment with intravenous immunoglobulin and there was significant improvement toward the end of 5th day. Though rare, this case report suggest that physician should remain vigilant for GBS following COVID-19 vaccination.

Delayed presentation of cannabis induced pancreatitis.

A thorough history and identifying risk factors are pivotal in establishing the cause of pancreatitis and preventing recurrences to curb the incidence of chronic pancreatitis and/or pancreatic cancer.

Cerebellar infarction as the initial presentation of IgG4-related disease.

Although IgG4-RD has CNS manifestations, cerebellar involvement has only been reported in three cases. Our patient presented with cerebellar symptoms, several cerebellar infarcts were evident on the brain MRI, and CT abdomen revealed retroperitoneal tumor. Endoscopic biopsy confirmed IgG4-RD. Steroids are the first-line therapy for IgG4-RD, but our patient was lost to follow-up before treatment.