Building Equitable Neuroscience Research Collaborations in Resource-limited Settings.

The burden of noncommunicable neurological disorders, such as stroke, dementia, and headache disorders, are on the rise in low- to middle-income countries (LMICs), while neuroinfectious diseases remain a major concern. The development of neuroscience research aimed at defining the burden of neurological diseases across the lifespan, as well as optimizing diagnosis and treatment strategies, is fundamental to improving neurological health in resource-limited settings. One of the key factors to advancing neuroscience research in LMICs is the establishment of effective collaborations based on responsible and trustworthy partnerships between local scientists in LMICs and international collaborators. LMIC researchers face many logistical, institutional, and individual level challenges as they embark on their neuroscience research journey. Despite these challenges, there are opportunities for improving LMIC investigator-led research that should focus on human and institutional infrastructure development. With regard to human capacity building, potential areas for offering support include enhancing research methodology training, offering instruction in manuscript and grant-writing, institutionalizing mentorship programs, and providing opportunities to conduct funded, mentored research to disseminate in high-impact journals. The foundational elements required for implementing and optimizing neuroscience research within an institution include an institutional review board, mentorship programs, data management, research administration, and laboratory facilities. This institutional capacity varies significantly across and within countries, and many rely on collaborations with better-resourced institutions to initiate research. Successful equitable collaborations ensure the engagement of all local and international stakeholders, as well as implementation of a self-sustaining long-term program. Building research capacity in LMICs is an essential endeavor that requires ongoing commitment to training independent scientists. As research capacity increases, LMIC institutions and governments should consider developing competitive research grant programs to support innovative studies led by local researchers, foster regional collaborations, and hence create a sustainable and independent neuroscience research environment.

Managing Post-Stroke Care During the COVID-19 Pandemic at a Tertiary Care Level Hospital in Peru.

OBJECTIVES: To understand the hospital-to-outpatient care transition and how the discharge process of stroke patients is managed; and to identify potential opportunities to improve these processes, while contrasting pre- and during COVID-19 experiences in Peru. METHODS: A qualitative study was conducted between February and March 2021 consisting of in-depth interviews of patients with stroke, their caregivers and healthcare personnel regarding stroke care at a national tertiary referral center for stroke care in Lima, Peru. We explored the following phases of the patients' journeys: pre-hospitalization, emergency room, hospitalization, discharge process and post-discharge. For each phase, we explored experiences, feelings and expectations using thematic analysis. RESULTS: We conducted a total of 11 interviews with patients or caregivers and 7 with health care personnel and found disruption in the continuity of care for patients with stroke. Mainly, caregivers and patients referred to problems related to communication with healthcare personnel and an absence of training to provide post-discharge care at home. Potential solutions included increasing human resources and caregiver participation in care, implementation of electronic healthcare records, improving the referral system and reinforcing telemedicine services. CONCLUSION: The continuity of care of patients with stroke was negatively affected during the COVID-19 pandemic. In LMICs, the impact was likely greater due to the already weak and fragmented healthcare systems. The COVID-19 pandemic presents an opportunity to improve post-stroke care services, and address patients' experiences and feelings by developing solutions in a participatory manner.

Global research priorities for infections that affect the nervous system.

Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

Challenges of Thrombolysis in a Developing Country: Characteristics and Outcomes in Peru.

BACKGROUND: The availability of intravenous tissue plasminogen activator (IV-tPA) remains limited worldwide, especially in low-income countries, where the burden of disability due to ischemic stroke is the highest. AIMS: To evaluate outcomes and safety of IV-tPA at the only Peruvian reference institute for neurologic diseases. METHODS: We conducted a prospective, observational study of stroke patients who received IV-tPA between 2009 and 2016. We assessed characteristics associated with good outcome (modified Rankine scale 0-2) at 3 months using a multivariate regression model; and factors correlated with clinical improvement (delta National Institute of Health Stroke Scale (NIHSS)) using linear regression. RESULTS: Only 1.98% (39/1,1962) of patients presenting with ischemic stroke received IV-tPA. Nearly half (41%) were younger than 60 years, 56.4 % were men, and most strokes were cardioembolic (46.2%). The majority (64.1%) were treated within 3-4.5 hours. The median NIHSS on admission and discharge was 9 and 4, respectively; 42.1% of patients had an mRS of 0-1 at 3 months. Three patients (7.7%) developed hemorrhagic conversion, and 1 patient died (2.6%). Patients with good outcomes had lower pretreatment systolic blood pressure (138.9 versus 158.1 mm Hg, P < .007), fewer complications during hospitalization (5 versus 9 events, P < .001), shorter hospital stay (14 versus 21 days, P < .03) and, paradoxically, longer last known well -to-door times (148.3 versus 105 minutes, P < .0022). Clinical improvement was associated with shorter door-to-tPA times and obesity. CONCLUSIONS: Our findings indicate that IV-tPA has similar safety and outcomes compared to developed countries. All internal metrics (door-to-tPA, door-to-CT, and CT-to-tPA time) improved over time, highlighting areas for future implementation science studies to further expedite the administration of IV-tPA.

Neurologic Infections in Travelers.

This review will provide an outline of the neurological complications of specific parasitic, bacterial, and viral infectious diseases that can affect the international traveler. We will discuss the epidemiology, life cycle, ecology, clinical manifestation, diagnosis, treatment, and prevention.

Mortality in hospitalized patients with tuberculous meningitis.

BACKGROUND: To evaluate the mortality in hospitalized patients with tuberculous meningitis and describe factors associated with an increased risk of mortality. METHODS: Retrospective study of hospitalized patients with tuberculous meningitis between 2006 and 2015 in Peru performing a generalized linear regression to identify factors predictive of in-hospital mortality. RESULTS: Of 263 patients, the median age was 35 years, 72.6% were men, 38% were positive for HIV upon admission, 24% had prior TB infections and 2.3% had prior MDR-TB infections. In-hospital mortality was 30.4% of all study patients with a final diagnosis of TBM. When multivariable analysis was applied, significant associations with in-hospital mortality were seen among patients with HIV (RR 2.06; Confidence Interval 95% (95% CI) 1.44-2.94), BMRC II (RR 1.78; 95% CI 1.07-2.97), BMRC III (RR 3.11; 95% CI 1.78-5.45) and positive CSF cultures (RR 1.95; 95% CI 1.39-2.74). CONCLUSIONS: In-hospital mortality is higher among patients with HIV infections, age over 40 years, positive CSF TB culture and BMRC stage II or III.

2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis.

The Infectious Diseases Society of America (IDSA) Standards and Practice Guidelines Committee collaborated with partner organizations to convene a panel of 10 experts on healthcare-associated ventriculitis and meningitis. The panel represented pediatric and adult specialists in the field of infectious diseases and represented other organizations whose members care for patients with healthcare-associated ventriculitis and meningitis (American Academy of Neurology, American Association of Neurological Surgeons, and Neurocritical Care Society). The panel reviewed articles based on literature reviews, review articles and book chapters, evaluated the evidence and drafted recommendations. Questions were reviewed and approved by panel members. Subcategories were included for some questions based on specific populations of patients who may develop healthcare-associated ventriculitis and meningitis after the following procedures or situations: cerebrospinal fluid shunts, cerebrospinal fluid drains, implantation of intrathecal infusion pumps, implantation of deep brain stimulation hardware, and general neurosurgery and head trauma. Recommendations were followed by the strength of the recommendation and the quality of the evidence supporting the recommendation. Many recommendations, however, were based on expert opinion because rigorous clinical data are not available. These guidelines represent a practical and useful approach to assist practicing clinicians in the management of these challenging infections.

A community-based cluster randomized survey of noncommunicable disease and risk factors in a peri-urban shantytown in Lima, Peru.

BACKGROUND: An estimated 863 million people-a third of the world's urban population-live in slums, yet there is little information on the disease burden in these settings, particularly regarding chronic preventable diseases. METHODS: From March to May 2012, we conducted a cluster randomized survey to estimate the prevalence of noncommunicable diseases (NCDs) and associated risk factors in a peri-urban shantytown north of Lima, Peru. Field workers administered a questionnaire that included items from the WHO World Health Survey and the WHO STEPS survey of chronic disease risk factors. We used logistic regression to assess the associations of NCDs and related risk factors with age and gender. We accounted for sampling weights and the clustered sampling design using statistical survey methods. RESULTS: A total of 142 adults were surveyed and had a weighted mean age of 36 years (range 18-81). The most prevalent diseases were depression (12%) and chronic respiratory disease (8%), while lifetime prevalence of cancer, arthritis, myocardial infarction, and diabetes were all less than 5%. Fifteen percent of respondents were hypertensive and the majority (67%) was unaware of their condition. Being overweight or obese was common for both genders (53%), but abdominal obesity was more prevalent in women (54% vs. 10% in men, p < 0.001). Thirty-five percent of men binge drank and 34% reported current smoking; these behaviors were less common among women (4% binge drank, p < 0.001; 8% smoked, p = 0.002). Increasing age was associated with an increased risk of abdominal obesity (Odds Ratio (OR) = 1.04, 95% CI = 1.01, 1.07, p = 0.02), hypertension (OR = 1.06, 95% CI = 1.02, 1.10, p = 0.006), arthritis (OR = 1.07, 95% CI = 1.03, 1.11, p < 0.001) and cancer (OR = 1.13, 95% CI = 1.07, 1.20, p < 0.001) in adjusted models. The prevalences of other NCDs and related risk factors were similar when stratified by age or gender. CONCLUSIONS: This study underlines the important burden of noncommunicable disease in informal settlements in Peru and suggests that prevention and treatment interventions could be optimized according to age and gender.

Outcomes and Experiences of Patients and Their Caregivers After Severe Stroke Requiring Tube Feeding in Peru.

OBJECTIVES: Evaluate clinical outcomes of stroke survivors in Peru discharged with artificial nutrition via a feeding tube (FT), and explore perspectives and experiences of these patients and their caregivers. METHODS: Retrospective chart review to describe the prevalence of FT placement and characteristics of patients admitted with stroke to the Instituto Nacional de Ciencias Neurológicas in Lima, Peru between January 2019 and 2021. Follow-up calls to stroke survivors discharged home with FTs or their caregivers included quantitative and qualitative questions to assess long-term outcome and explore perspectives around poststroke care and FT management. We analyzed quantitative data descriptively and applied thematic analysis to qualitative data using a consensus-driven codebook. RESULTS: Of 812 hospitalized patients with stroke, 146 (18%) were discharged home with FT, all with nasogastric tubes (NGTs). Follow-up calls were performed a median of 18 months after stroke with 96 caregivers and three patients. Twenty-five patients (25%) had died, and 82% of survivors (n = 61) remained dependent for some care. Four themes emerged from interviews: (1) perceived suffering (physical, emotional, existential) associated with the NGT and stroke-related disability, often exacerbated by lack of preparedness or prognostic awareness; (2) concerns around compromised personhood and value-discordant care; (3) coping with their loved-one's illness and the caregiving role; and (4) barriers to NGT care and skill acquisition. CONCLUSION: We identified a high burden of palliative and supportive needs among severe stroke survivors with NGTs and their caregivers suggesting opportunities to improve poststroke care through education, communication, and support.

Scoping review of measures of treatment burden in patients with multimorbidity: advancements and current gaps.

OBJECTIVES: To identify, assess, and summarize the measures to assess burden of treatment in patients with multimorbidity (BoT-MMs) and their measurement properties. STUDY DESIGN AND SETTING: MEDLINE via PubMed was searched from inception until May 2021. Independent reviewers extracted data from studies in which BoT-MMs were developed, validated, or reported as used, including an assessment of their measurement properties (e.g., validity and reliability) using the COnsensus-based Standards for the selection of health Measurement INstruments. RESULTS: Eight BoT-MMs were identified across 72 studies. Most studies were performed in English (68%), in high-income countries (90%), without noting urban-rural settings (90%). No BoT-MMs had both sufficient content validity and internal consistency; some measurement properties were either insufficient or uncertain (e.g., responsiveness). Other frequent limitations of BoT-MMs included absent recall time, presence of floor effects, and unclear rationale for categorizing and interpreting raw scores. CONCLUSION: The evidence needed for use of extant BoT-MMs in patients with multimorbidity remains insufficiently developed, including that of suitability for their development, measurement properties, interpretability of scores, and use in low-resource settings. This review summarizes this evidence and identifies issues needing attention for using BoT-MMs in research and clinical practice.

Tuberculosis of the central nervous system in immunocompromised patients: HIV infection and solid organ transplant recipients.

Central nervous system (CNS) tuberculosis (TB) is a devastating infection with high rates of morbidity and mortality worldwide and may manifest as meningitis, tuberculoma, abscess, or other forms of disease. Immunosuppression, due to either human immunodeficiency virus infection or solid organ transplantation, increases susceptibility for acquiring or reactivating TB and complicates the management of underlying immunosuppression and CNS TB infection. This article reviews how immunosuppression alters the clinical presentation, diagnosis, treatment, and outcome of TB infections of the CNS.

Human papillomavirus infection in female sex workers in Lima, Peru.

OBJECTIVES: To determine the prevalence and risk factors for human papillomavirus (HPV) infection in female sex workers (FSW) in Lima, Peru. METHODS: Cross-sectional study of 87 FSW. Information regarding demographics, sex work practices, and genital and blood specimens was collected. RESULTS: Forty-four (50.6%) of 87 FSW had HPV detected in cervical swabs. The prevalence of coinfection by two or more HPV types was 39.1%. Thirty-one (35.6%) were infected by at least one high-risk HPV type, representing 70.5% of women with HPV infection. HPV infection was associated with younger age but not with any demographic or sexual characteristics. CONCLUSIONS: Our study confirms the high prevalence of HPV infection in FSW reported by other groups and suggests that brothel-based FSW may be at lower risk for acquiring high-risk HPV infection.

Tuberculous Meningitis: Impact of Timing of Treatment Initiation on Mortality.

We conducted a retrospective cross-sectional study of adult hospitalized patients with confirmed tuberculous meningitis to determine the impact of the timing of treatment initiation on mortality. The mortality of tuberculous meningitis patients was high and was associated with delay in initiation of treatment, older age, HIV infection, and higher disease severity at admission.

Prevalence of stroke survival in rural communities living in northern Peru.

BACKGROUND AND PURPOSE: Stroke is the leading cause of neurological impairment in the South American Andean region. However, the epidemiology of stroke in the region has been poorly characterized. METHODS: We conducted a staged three-phase population-based study applying a validated eight-question neurological survey in 80 rural villages in Tumbes, northern Peru, then confirmed presence or absence of stroke through a neurologist's examination to estimate the prevalence of stroke. RESULTS: Our survey covered 90% of the population (22,278/24,854 individuals, mean age 30±21.28, 48.45% females), and prevalence of stroke was 7.05/1,000 inhabitants. After direct standardization to WHO's world standard population, adjusted prevalence of stroke was 6.94/1,000 inhabitants. Participants aged ≥85 years had higher stroke prevalence (>50/1000 inhabitants) compared to other stratified ages, and some unusual cases of stroke were found among individuals aged 25-34 years. The lowest age reported for a first stroke event was 16.8 years. High blood pressure (aPR 4.2 [2.7-6.4], p>0.001), and sedentary lifestyle (aPR 1.6 [1.0-2.6], p = 0.045) were more prevalent in people with stroke. CONCLUSIONS: The age-standardized prevalence of stroke in this rural coastal Peruvian population was slightly higher than previously reported in studies from surrounding rural South American settings, but lower than in rural African and Asian regions. The death rate from stroke was much higher than in industrialized and middle-income countries.

Elevated Plasma von Willebrand Factor Levels Are Associated With Subsequent Ischemic Stroke in Persons With Treated HIV Infection.

Background: We assessed whether key biomarkers of endothelial activation and hemostasis/thrombosis were elevated in individuals receiving effective antiretroviral therapy (ART) in the year before ischemic stroke. Methods: We conducted a case-control study nested in the CFAR Network of Integrated Clinical Systems cohort, comparing 42 adjudicated cases with ischemic stroke with 83 controls matched for ART regimen. Angiopoietin-1, angiopoietin-2, C-reactive protein, interleukin-6, plasminogen activation inhibitor-1, P-selectin, serum amyloid-A, soluble CD14, ICAM-1, VCAM-1, apolipoprotein A1, ADAMTS13, and von Willebrand factor (VWF) were measured in stored plasma collected before the stroke event. We used conditional logistic regression to identify associations with ischemic stroke, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores. Results: After adjustment for age and sex, higher plasma viral load and higher angiopoeitin-2, soluble CD14, and VWF were associated with increased odds of ischemic stroke; higher nadir CD4 count was associated with decreased odds of ischemic stroke. VWF remained associated with subsequent ischemic stroke after adjustment for ASCVD score (adjusted odds, 1.74; 95% CI, 1.01-2.98 per log2 increment). In a separate model adjusting for VACS score, only VWF (adjusted odds, 1.80; 95% CI, 1.04-3.12 per log2 increment) was associated with subsequent ischemic stroke. In a sensitivity analysis excluding participants with viral load ≥400 copies/mL, associations between VWF and ischemic stroke were attenuated, with risk estimates ranging from 1.59 to 1.64 per log2 increment. Conclusions: Endothelial activation and related release and attachment of VWF may play an important role in ischemic stroke among persons with treated HIV infection.

Types of Stroke Among People Living With HIV in the United States.

BACKGROUND: Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes. SETTING: CNICS, a U.S. multisite clinical cohort of PLWH in care. METHODS: We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort. RESULTS: Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes. CONCLUSION: Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH.

Intimate Partner Violence, Poverty, and Maternal Health Care-Seeking Among Young Women in Kenya: a Cross-Sectional Analysis Informing the New Sustainable Development Goals.

BACKGROUND: Despite considerable achievements associated with the MDGs, under-five mortality, particularly in Sub-Saharan Africa, remains alarmingly high. Globally, intimate partner violence (IPV) affects one in three women within their lifetime. Little is known about the relationship between IPV and maternal care-seeking in the context of high rates of under-five mortality, particularly among young women and adolescent girls in low- and middle-income countries (LMICs). METHODS: Data from the Kenya Demographic Health Survey (2008-2009) were limited to a sample of women aged 15-24 years (n=1,406) with a child under-five who had experienced IPV in the last 12 months. Using multivariate logistic regression, we constructed three models: 1) base model; 2) controlling for type of residence (urban/rural); and 3) controlling for wealth status and education attainment, to estimate odds ratios (ORs) for the association between IPV and ten maternal care-seeking behaviors. RESULTS: Thirty-eight percent of the women had experienced some form of intimate partner violence in the last 12 months. Women who had experience IPV were less likely: 1) to complete a minimum of 4 antenatal visits after single IPV exposure (OR=0.61, 95% CI=0.44, 0.86 and after severe IPV (OR=0.80; 95% CI=0.44, 0.88) and 2) to deliver in health facility after severe IPV exposure (OR=0.74; 95% CI=0.54, 0.89), both adjusted for educational attainment and wealth status. Lower socio-economic status and living in a rural area were strongly associated with increased likelihood of IPV. CONCLUSIONS: Intersectional approaches that consciously focus on, and creatively address IPV may be key to the success of reducing child mortality and improving maternal health outcomes. The implementation of joint programming and development of combination interventions to effectively reduce the risk of exposure to IPV and promote maternal care-seeking behavior are needed to improve child morbidity and mortality in LMICs.

Diagnosis of neurocysticercosis by detection of Taenia solium DNA using a global DNA screening platform.

Neurocysticercosis is caused by Taenia solium infection of the brain. Diagnosis is most often made by visualization of the parasitic scolex by magnetic resonance imaging of the brain or by characteristic neuroimaging findings with serologic test results positive for T. solium. A patient who presents with a solitary brain lesion usually poses a diagnostic dilemma, because the differential diagnosis often includes neurocysticercosis and other infections or neoplasm. Although the sensitivity of serologic testing for T. solium approaches 100% in patients with multiple intraparenchymal cysts, the sensitivity of testing for patients with solitary cysts is <50%, which makes serologic testing a less useful diagnostic tool for patients with solitary central nervous system (CNS) lesions. We describe 2 patients with solitary CNS lesions who received a neurocysticercosis diagnosis after identification of T. solium DNA in brain biopsy tissue with use of a global DNA screening platform. Global screening is a promising tool for the diagnosis of CNS infection, especially when traditional diagnostic tools are insensitive.