Neuroinvasive West Nile Virus Infection in Immunosuppressed and Immunocompetent Adults.

Importance: West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored. Objective: To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS. Design, Setting, and Participants: This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023. Exposure: Immunosuppresion. Main Outcomes and Measures: Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS. Results: Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64). Conclusions and Relevance: In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.

Consensus Competencies for Postgraduate Fellowship Training in Global Neurology.

BACKGROUND AND OBJECTIVES: Use a modified Delphi approach to develop competencies for neurologists completing ≥1 year of advanced global neurology training. METHODS: An expert panel of 19 United States-based neurologists involved in global health was recruited from the American Academy of Neurology Global Health Section and the American Neurological Association International Outreach Committee. An extensive list of global health competencies was generated from review of global health curricula and adapted for global neurology training. Using a modified Delphi method, United States-based neurologists participated in 3 rounds of voting on a survey with potential competencies rated on a 4-point Likert scale. A final group discussion was held to reach consensus. Proposed competencies were then subjected to a formal review from a group of 7 neurologists from low- and middle-income countries (LMICs) with experience working with neurology trainees from high-income countries (HICs) who commented on potential gaps, feasibility, and local implementation challenges of the proposed competencies. This feedback was used to modify and finalize competencies. RESULTS: Three rounds of surveys, a conference call with United States-based experts, and a semistructured questionnaire and focus group discussion with LMIC experts were used to discuss and reach consensus on the final competencies. This resulted in a competency framework consisting of 47 competencies across 8 domains: (1) cultural context, social determinants of health and access to care; (2) clinical and teaching skills and neurologic medical knowledge; (3) team-based practice; (4) developing global neurology partnerships; (5) ethics; (6) approach to clinical care; (7) community neurologic health; (8) health care systems and multinational health care organizations. DISCUSSION: These proposed competencies can serve as a foundation on which future global neurology training programs can be built and trainees evaluated. It may also serve as a model for global health training programs in other medical specialties as well as a framework to expand the number of neurologists from HICs trained in global neurology.

Is Intravenous Immunoglobulin Effective in Reducing the Risk of Mortality and Morbidity in Neuroinvasive West Nile Virus Infection?: A Critically Appraised Topic.

BACKGROUND: The clinical benefit of intravenous immunoglobulin (IVIG) in adult individuals with neuroinvasive West Nile virus (niWNV) infection is not well substantiated. We sought to critically assess current evidence regarding the efficacy of IVIG in treating patients with niWNV. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-infectious diseases. RESULTS: The appraised study enrolled 62 participants with suspected niWNV, randomized into 3 different arms [37 participants in the Omr-IgG-am group, 12 in the Polygam group, and 13 in the normal saline (NS) group]. Omr-IgG-am and Polygam are different formulations of IVIG. IVIG safety, measured as rates of serious adverse events, was the primary study outcome while IVIG efficacy, measured as rates of unfavorable outcomes, was a secondary endpoint. The estimated rates of SAE were statistically similar in all groups (51.4% Omr-IgG-am, 58.3% Polygam, and 23.1% NS groups). Unfavorable outcomes also occurred at a similar rate between all the groups (51.5% Omr-IgG-am, 54.5% Polygam, and 27.3% NS). CONCLUSIONS: The appraised trial showed that Omr-IgG-am and Polygam are as safe as NS. Data on efficacy from this trial were limited by a small sample size. Phase III clinical trials on IVIG efficacy in NiWNV infection are needed.

Hirayama Disease: A 15-Year-Old Male With Progressive Distal Right Upper Extremity Weakness.

INTRODUCTION: Hirayama disease is a rare neuromuscular disorder characterized by abnormal forward displacement of the cervical spinal cord, resulting in focal ischemic changes of anterior horn cells. CASE REPORT: A 15-year-old male presented with 6 months of progressive right upper extremity weakness. Electromyography/nerve conduction study indicated a chronic neurogenic process involving the C8-T1 myotome. Cervical spine magnetic resonance imaging in the neutral position demonstrated minor disk bulges without significant spinal canal narrowing. With flexion, there was a forward displacement of the dorsal dural sac and marked effacement of the subarachnoid spaces from vertebral levels C5 through C7. In addition, prominent flow voids were now seen in the dorsal epidural space consistent with engorged venous structures. CONCLUSION: The diagnosis of Hirayama disease requires a high index of suspicion, and imaging should include a series with the neck in a flexed position, as imaging in the neutral position is often unrevealing and the disorder can otherwise easily be missed.

HIV Infection and 90-Day Stroke Outcomes in Uganda: A Prospective Observational Cohort Study.

Background and Objectives: Little is known about the impact of HIV infection on the clinical presentation and outcomes after stroke in the modern antiretroviral therapy (ART) era. We aimed to compare stroke characteristics and outcomes between persons with HIV (PWH) and without HIV (PWOH) presenting with stroke in Uganda. Methods: We conducted a matched cohort study at Mulago National Referral Hospital and Mbarara Regional Referral Hospital between January 2018 and November 2020. We enrolled consecutive PWH presenting with CT-confirmed acute or subacute stroke (symptom onset ≤14 days) and matched them by sex and stroke type to 2 consecutive available PWOH admitted to the same hospital. We obtained baseline clinical data and followed participants for 90 days from the day of clinical presentation. We compared stroke severity (defined by the NIH stroke scale [NIHSS]) and 90-day all-cause mortality and morbidity (using the modified Rankin Scale [mRS]) by HIV serostatus with and without adjustment for confounders. Results: We enrolled 105 PWH and 157 PWOH with stroke. PWH were younger (mean [SD] age 49 [14] vs 59 [16] years, p < 0.001), and nearly 80% (82/105) were on ART for a median of 5 years and a median CD4 count of 214 cells/uL (interquartile range 140, 337). Compared with PWOH, PWH presented with a 3-point lower median NIHSS (16 vs 19, p = 0.011), a 20% lower proportion of all-cause mortality at 90 days (p = 0.001), and had less disability at 90 days (median mRS 4 vs 5, p = 0.004). Age and NIHSS-adjusted odds ratio of 90-day all-cause mortality in PWH compared with PWOH was 0.45 (95% CI 0.22-0.96, p = 0.037). Discussion: In the modern ART era, PWH with acute stroke in Uganda present with modest stroke and are significantly less likely to die within 90 days than PWOH. This potentially reflects the protective effects of ART, enhanced health care access, and their younger age at stroke presentation.

An Analysis of Stroke Risk Factors by HIV Serostatus in Uganda: Implications for Stroke Prevention in Sub-Saharan Africa.

OBJECTIVE: HIV infection is an important stroke risk factor in sub-Saharan Africa.  However, data on stroke risk factors in the era of antiretroviral therapy (ART) are sparse. We aimed to determine if stroke risk factors differed by HIV serostatus in Uganda. METHODS: We conducted a matched cohort study, enrolling persons living with HIV (PWH) with acute stroke, matched by sex and stroke type to HIV uninfected (HIV-) individuals. We collected data on stroke risk factors and fitted logistic regression models for analysis. RESULTS: We enrolled 262 participants:105 PWH and 157 HIV-. The median ART duration was 5 years, and the median CD4 cell count was 214 cells/uL. PWH with ischemic stroke had higher odds of hypertriglyceridemia (AOR 1.63; 95% CI 1.04, 2.55, p=0.03), alcohol consumption (AOR 2.84; 95% CI 1.32, 6.14, p=0.008), and depression (AOR 5.64; 95%CI 1.32, 24.02, p=0.02) while HIV- persons with ischemic stroke were more likely to be > 55 years of age (AOR 0.43; 95%CI 0.20-0.95, p=0.037), have an irregular heart rhythm (AOR 0.31; 95%CI 0.10-0.98, p=0.047) and report low fruit consumption (AOR 0.39; 95%CI 0.18-0.83, p=0.014).  Among all participants with hemorrhagic stroke (n=78) we found no differences in the prevalence of risk factors between PWH and HIV-. CONCLUSIONS: PWH with ischemic stroke in Uganda present at a younger age, and with a combination of traditional and psychosocial risk factors. By contrast, HIV- persons more commonly present with arrhythmia. A differential approach to stroke prevention might be needed in these populations.

Current Guidelines on Management of Amaurosis Fugax and Transient Ischemic Attacks.

ABSTRACT: Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction resulting from focal brain, spinal cord, or retinal ischemia, without associated infarction. Consequently, a TIA encompasses amaurosis fugax (AF) that is a term used to denote momentary visual loss from transient retinal ischemia. In this review, we use the word TIA to refer to both cerebral TIAs (occurring in the brain) and AF (occurring in the retina). We summarize the key components of a comprehensive evaluation and management of patients presenting with cerebral and retinal TIA.All TIAs should be treated as medical emergencies, as they may herald permanent disabling visual loss and devastating hemispheric or vertebrobasilar ischemic stroke. Patients with suspected TIA should be expeditiously evaluated in the same manner as those with an acute stroke. This should include a detailed history and examination followed by specific diagnostic studies. Imaging of the brain and extracranial and intracranial blood vessels forms the cornerstone of diagnostic workup of TIA. Cardiac investigations and serum studies to evaluate for etiological risk factors are also recommended.The management of all TIAs, whether cerebral or retinal, is similar and should focus on stroke prevention strategies, which we have categorized into general and specific measures. General measures include the initiation of appropriate antiplatelet therapy, encouraging a healthy lifestyle, and managing traditional risk factors, such as hypertension, dyslipidemia, and diabetes. Specific management measures require the identification of a specific TIA etiology, such as moderate-severe (greater than 50% of stenosis) symptomatic extracranial large vessel or intracranial steno-occlusive atherosclerotic disease, aortic arch atherosclerosis, and atrial fibrillation.

Stroke Features, Risk Factors, and Pathophysiology in SARS-CoV-2-Infected Patients.

OBJECTIVE: To provide a comprehensive description of stroke characteristics, risk factors, laboratory parameters, and treatment in a series of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients admitted to Mayo Clinic hospitals in Rochester, Minnesota; Jacksonville, Florida; and Phoenix, Arizona, as well as the Mayo Clinic Health System. PATIENTS AND METHODS: We retrospectively identified hospitalized patients in whom stroke and SARS-CoV-2 infection were diagnosed within the same 3-month interval between September 8, 2019, and December 31, 2020. and extracted data on all available variables of interest. We further incorporated our findings into the existing body of basic science research to present a schematic model illustrating the proposed pathogenesis of ischemic stroke in SARS-CoV-2-infected patients. RESULTS: We identified 30 cases during the study period, yielding a 0.5% stroke rate across 6381 SARS-CoV-2-infected hospitalized patients. Strokes were ischemic in 26 of 30 individuals and hemorrhagic in 4 of 30. Traditional risk factors were common including hypertension (24 of 30), hyperlipidemia (18 of 30), smoking history (13 of 30), diabetes (11 of 30), and atrial fibrillation (8 of 30). The most common ischemic stroke mechanisms were cardioembolism (9 of 26) and cryptogenic (9 of 26). Intravenous alteplase and mechanical thrombectomy were administered to 2 of 26 and 1 of 26, respectively. The median (interquartile range) serum C-reactive protein, interleukin-6, D-dimer, fibrinogen, and ferritin levels were 66 (21-210) mg/L, 116 (8-400) pg/mL, 1267 (556-4510) ng/mL, 711 (263-772) mg/dL, and 407 (170-757) mcg/L, respectively, which were elevated in individuals with available results. CONCLUSION: The high prevalence of vascular risk factors and concurrent elevation of proinflammatory and procoagulation biomarkers suggest that there is an interplay between both factors in the pathogenesis of stroke in SARS-CoV-2-infected patients.

HIV Infection Is an Independent Predictor of Mortality Among Adults with Reduced Level of Consciousness in Uganda.

The clinical epidemiology of adults admitted with reduced level of consciousness (LOC) in sub-Saharan Africa (SSA) and the impact of HIV infection on the risk of mortality in this population is unknown. We secondarily analyzed data from a cohort study that enrolled 359 consecutive adults with reduced LOC presenting to Mbarara Regional Hospital in Uganda with the aim of comparing the prognostic utility of the Full Outline of Unresponsiveness (FOUR) score to the Glasgow Coma Scale (GCS) Score. For this analysis, we included 336 individuals with known HIV serostatus, obtaining clinical, laboratory, and follow-up data. We recorded investigations and treatments deemed critical by clinicians for patient care but were unavailable. We computed mortality rates and used logistic regression to determine predictors of 30-day mortality. The median GCS was 10. Persons living with HIV infection (PLWH) accounted for 97 of 336 (29%) of the cohort. The 30-day mortality rate in the total cohort was 148 of 329 (45%), and this was significantly higher in PLWH (57% versus 40%, adjusted odds ratio [aOR] 2.39: 95% confidence interval [CI]: 1.31-4.35, P = 0.0046). Other predictors of mortality were presence of any unmet clinical need (aOR 1.72; 95% CIL 1.04-2.84, P = 0.0346), anemia (aOR 1.68; 95% CI: 1.01-2.81, P = 0.047), and admission FOUR score < 12 [aOR 4.26; 95% CI: 2.36-7.7, P < 0.0001). Presentation with reduced LOC in Uganda is associated with high mortality rates, with worse outcomes in PLWH. Improvement of existing acute care services is likely to improve outcomes.

Population Pharmacokinetics and Significant Under-Dosing of Anti-Tuberculosis Medications in People with HIV and Critical Illness.

Critical illness from tuberculosis (TB) bloodstream infection results in a high case fatality rate for people living with human immunodeficiency virus (HIV). Critical illness can lead to altered pharmacokinetics and suboptimal drug exposures. We enrolled adults living with HIV and hospitalized with sepsis, with and without meningitis, in Mbarara, Uganda that were starting first-line anti-TB therapy. Serum was collected two weeks after enrollment at 1-, 2-, 4-, and 6-h post-dose and drug concentrations quantified by validated LC-MS/MS methods. Non-compartmental analyses were used to determine total drug exposure, and population pharmacokinetic modeling and simulations were performed to determine optimal dosages. Eighty-one participants were enrolled. Forty-nine completed pharmacokinetic testing: 18 (22%) died prior to testing, 13 (16%) were lost to follow-up and one had incomplete testing. Isoniazid had the lowest serum attainment, with only 4.1% achieving a target exposure over 24 h (AUC0-24) of 52 mg·h/L despite appropriate weight-based dosing. Simulations to reach target AUC0-24 found necessary doses of rifampin of 1800 mg, pyrazinamide of 2500-3000 mg, and for isoniazid 900 mg or higher. Given the high case fatality ratio of TB-related critical illness in this population, an early higher dose anti-TB therapy should be trialed.

Prognostic Utility of Daily Changes in Glasgow Coma Scale and the Full Outline of Unresponsiveness Score Measurement in Patients with Metabolic Encephalopathy, Central Nervous System Infections and Stroke in Uganda.

BACKGROUND: Metabolic encephalopathy (ME), central nervous system (CNS) infections, and stroke are common causes of reduced level of consciousness in Uganda. However, the prognostic utility of changes in the daily measurements of the Full Outline of Unresponsiveness (FOUR) score and Glasgow Coma Scale (GCS) score in these specific disorders is not known. METHODS: We conducted secondary analyses of data from patients who presented with reduced level of consciousness due to CNS infections, stroke, or ME to a tertiary hospital in Uganda. Patients had FOUR/GCS scores at admission and at 24 and 48 h. We calculated a change in FOUR score (ΔFOUR) and change in GCS score (ΔGCS) at 24 and 48 h and used logistic regression models to determine whether these changes were predictive of 30-day mortality. In addition, we determined the prognostic utility of adding the admission score to the 24-h ΔFOUR and 24-h ΔGCS on mortality. RESULTS: We analyzed data from 230 patients (86 with ME, 79 with CNS infections, and 65 with stroke). The mean (SD) age was 50.8 (21.3) years, 27% (61 of 230) had HIV infection, and 62% (134 of 230) were peasant farmers. ΔFOUR at 24 h was predictive of mortality among those with ME (odds ratio [OR] 0.64 [95% confidence interval {CI} 0.48-0.84]; p = 0.001) and those with CNS infections (OR 0.65 [95% CI 0.48-0.87]; p = 0.004) but not in those with stroke (OR 1.0 [95% CI 0.73-1.38]; p = 0.998). However, ΔGCS at 24 h was only predictive of mortality in the ME group (OR 0.69 [95% CI 0.56-0.86]; p = 0.001) and not in the CNS or stroke group. This 24-h ΔGCS and ΔFOUR pattern was similar at 48 h in all subgroups. The addition of an admission score to either 24-h ΔFOUR or 24-h ΔGCS significantly improved the predictive ability of the scores in those with stroke and CNS infection but not in those with ME. CONCLUSIONS: Twenty-four-hour and 48-h ΔFOUR and ΔGCS are predictive of mortality in Ugandan patients with CNS infections and ME but not in those with stroke. For individuals with stroke, the admission score plays a more significant predictive role that the change in scores.