Candida Dublinensis Meningitis in an Immunocompetent Host: A Case Report and Review of the Literature.

Objectives: This study presents a case of Candida dubliniensis meningitis in an immunocompetent injection drug user and provides a literature review of CNS infections related to C dubliniensis. Methods: A 32-year-old man with a history of opioid use disorder presented with seizures and underwent extensive diagnostic evaluations, including imaging, lumbar puncture, and tissue biopsies. Treatment consisted of antifungal therapy and placement of ventriculoperitoneal shunt (VPS). Results: C dublinensis meningitis was identified on culture from a posterior fossa arachnoid sample. The patient demonstrated leptomeningeal enhancement on imaging, which resolved following 20 weeks of fluconazole. The development of hydrocephalus necessitated placement of VPS. Additional published cases of C dublinensis meningitis revealed varying presentations, diagnostic methods, and treatment regimens. Discussion: C dublinensis meningitis is a rare condition affecting both immunocompromised and immunocompetent individuals, particularly those with intravenous drug use. The diagnosis can be challenging, often requiring repeat lumbar punctures, extensive CSF sampling, or meningeal biopsy. Treatment involves a combination of antifungal agents, such as amphotericin B and fluconazole. Intracranial hypertension and hydrocephalus may necessitate surgical intervention. In conclusion, C dublinensis meningitis should be considered as a potential etiology of meningitis, particularly in those with a history of injection drug use.

Imaging of congenital and developmental cystic lesions of the brain: a narrative review.

INTRODUCTION: Congenital and developmental intracranial cysts represent a large heterogenous group with varied presentations and etiologies. They can range from normal variants to pathologic lesions often associated with known congenital syndromes or acquired insults. While some are incidentally found, others are symptomatic or may become symptomatic over time. The preferred type of neuroimaging for timely diagnosis helps determine appropriate management and treatment, if indicated. AREAS COVERED: In this narrative review article, authors present a comprehensive description of developmental cystic lesions. Imaging descriptions are provided for each type of cystic lesion as well as several representative images. EXPERT OPINION: As advanced neuroimaging techniques become more ubiquitous in clinical use, more light may be shed on the natural history of certain intracranial cystic lesions throughout the lifespan. This includes prenatal imaging for early identification and prognostication to surveillance imaging into advanced age to ascertain associations of certain cystic lesions with age-related cognitive dysfunction.

Gummatous Neurosyphilis With Transient Worsening of Neurological Symptoms After Treatment Initiation.

Cerebral syphilitic gumma is an atypical presentation of neurosyphilis, the clinical manifestations of which depend on the size and location of the lesions. It radiologically presents as enhancing nodular lesion(s) in brain parenchyma. We present a case of a patient with cerebral syphilitic gummas who had worsening neurological symptoms a few hours after initiation of anti-syphilitic antibiotic treatment. We aim to illustrate the clinical and radiological characteristics that might be helpful to clinicians when approaching the challenges they might encounter while treating neurosyphilis.

Strokes in Patients With Injection Drug Use and Tricuspid Valve Endocarditis - A Case Series.

Research Design: In this study, we describe patients from a tertiary care safety-net hospital endocarditis registry with tricuspid valve infective endocarditis (TVIE), and concomitant acute or subacute ischemic stroke predominantly associated with injection drug use (IDU). We retrospectively obtained data pertinent to neurologic examinations, history of injection drug use (IDU), blood cultures, transthoracic/transesophageal echocardiography (TTE/TEE), neuroimaging, and Modified Rankin Scale (mRS) scores at discharge. Only those patients with bacteremia, tricuspid valve vegetations, and neuroimaging consistent with acute to subacute ischemic infarction and microhemorrhages in two cases were included in this series. Results: Of 188 patients in the registry, 66 patients had TVIE and 10 of these were complicated by ischemic stroke. Neurologic symptoms were largely non-specific, eight patients had altered mental status and only 3 had focal deficits. Nine cases were associated with IDU. Two patients had evidence of a patent foramen ovale on echocardiography. Blood cultures grew S. aureus species in 9 of the patients, all associated with IDU. Three patients died during hospitalization. The mRS score at discharge for survivors ranged 0-4. Conclusions: Patients with strokes from TVIE had heterogeneous presentations and putative mechanisms. We noted that robust neuroimaging is lacking for patients with TVIE from IDU and that such patients may benefit from neuroimaging as a screen for strokes to assist peri-operative management. Further inquiry is needed to elucidate stroke mechanisms in these patients.

Characteristics and evolution of cerebral aneurysms among adults living with HIV: A retrospective, longitudinal case series.

OBJECTIVE: Previous research indicates an increased risk of cerebral aneurysm formation in adults living with human immunodeficiency virus (ALWH), however there are few longitudinal studies on the risk factors for and outcomes of cerebral aneurysms in this population. We aim to describe the characteristics and evolution of cerebral aneurysms in a large cohort of ALWH. MATERIALS AND METHODS: A chart review was completed for all adults evaluated at an urban, safety-net U.S. hospital between January 1, 2000, and October 22, 2021, with history of both HIV and at least one cerebral aneurysm. RESULTS: A total of 82 cerebral aneurysms were identified amongst 50 patients (52% female sex). Forty-six percent of patients with a nadir CD4 count less than 200 cells/mm3 (N=13) and 44% of patients with maximum viral load >10,000 copies/mL (N=18) developed new aneurysms or were found to have aneurysm growth over time compared with 29% of patients with a CD4 nadir above 200 cells/mm3 (N=21) and 22% of patients with maximum viral load

COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.

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.

Imaging of infectious and inflammatory cystic lesions of the brain, a narrative review.

INTRODUCTION: Intracranial cysts and cyst-like intracranial lesions are common findings on neuroimaging with a wide range of etiologies. Oftentimes, cystic intracranial lesions are benign but in some parts of the world, infectious etiologies for cystic lesions in the brain are quite common. Prompt identification of the cause of a cystic brain lesion is paramount in determining appropriate treatment if indicated. AREAS COVERED: In this narrative review article, the authors present a comprehensive description of cystic lesions of infectious or inflammatory etiology. Imaging descriptions are provided for each type of cystic lesion as well as several representative images. EXPERT OPINION: The majority of diagnoses may be identified by CT and MR imaging. Yet some pathologies are still unable to be determined through standard imaging techniques and biopsy remains necessary for definitive diagnosis in some cases. Advanced neuroimaging such as metabolic/nuclear imaging and advanced MR hold promise with improved diagnostics but are not often available in geographic regions where these illnesses are endemic.

A machine learning eye movement detection algorithm using electrooculography.

STUDY OBJECTIVES: Eye movement quantification in polysomnograms (PSG) is difficult and resource intensive. Automated eye movement detection would enable further study of eye movement patterns in normal and abnormal sleep, which could be clinically diagnostic of neurologic disorders, or used to monitor potential treatments. We trained a long short-term memory (LSTM) algorithm that can identify eye movement occurrence with high sensitivity and specificity. METHODS: We conducted a retrospective, single-center study using one-hour PSG samples from 47 patients 18-90 years of age. Team members manually identified and trained an LSTM algorithm to detect eye movement presence, direction, and speed. We performed a 5-fold cross validation and implemented a "fuzzy" evaluation method to account for misclassification in the preceding and subsequent 1-second of gold standard manually labeled eye movements. We assessed G-means, discrimination, sensitivity, and specificity. RESULTS: Overall, eye movements occurred in 9.4% of the analyzed EOG recording time from 47 patients. Eye movements were present 3.2% of N2 (lighter stages of sleep) time, 2.9% of N3 (deep sleep), and 19.8% of REM sleep. Our LSTM model had average sensitivity of 0.88 and specificity of 0.89 in 5-fold cross validation, which improved to 0.93 and 0.92 respectively using the fuzzy evaluation scheme. CONCLUSION: An automated algorithm can detect eye movements from EOG with excellent sensitivity and specificity. Noninvasive, automated eye movement detection has several potential clinical implications in improving sleep study stage classification and establishing normal eye movement distributions in healthy and unhealthy sleep, and in patients with and without brain injury.

Surgical outcomes of pulmonary valve infective endocarditis: A US population-based analysis.

BACKGROUND: Pulmonary valve infective endocarditis (PVIE) represents a rare subset of right-sided IE. This study aimed to evaluate the population-level surgical outcomes of PVIE in the United States. METHODS: We performed a retrospective observational study using the 2002-2017 National Inpatient Sample database. We included hospitalizations with both IE and PV interventions. We excluded Tetralogy of Fallot, congenital PV malformation, and those who underwent the Ross procedure. The primary outcome was in-hospital mortality. The secondary outcomes included major complications and length of hospital stay. RESULTS: We identified 677 PVIE hospitalizations that underwent surgical treatment, accounting for 0.06% of all IE hospitalizations. The mean age was 35.2 ± 1.7 years; 60.0% were White, 30.3% were women, and 11.4% were intravenous drug users. Most were treated in large-sized (70.1%) urban teaching (88.8%) hospitals. Close to 30% of patients received at least one concomitant valve procedure. The in-hospital mortality was 5.5% for the entire cohort, and the median length of stay was 16 days. Major complications included complete heart block (8.7%), acute kidney injury (8.1%), and stroke (1.3%). The differences in mortality and complications rate comparing PV repair and replacement were not statistically significant. PV repair was associated with a longer length of hospital stay compared to PV replacement (median: 25 vs. 16 days, p = 0.03). CONCLUSIONS: This study defines the population-level in-hospital outcomes after surgical intervention of PVIE. Surgically treated PVIE patients are associated with relatively low mortality and morbidities. The outcomes between PV replacement and repair are similar.

Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.

To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS: None. RESULTS: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001). CONCLUSIONS: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

COVID-19 and the brain.

Entering the third year into the pandemic, overwhelming evidence demonstrates that Coronavirus disease 2019 (COVID-19) infection is a systemic illness, often with involvement of the central nervous system. Multiple mechanisms may underlie the development of neurologic manifestations of illness, including hypoxia, systemic illness, hypercoagulability, endothelial dysfunction, general critical illness, inflammatory response, and neurotropism of the severe acute respiratory syndrome coronavirus 2 (SARS-Co-V2) virus. COVID-19 infection is associated with neurologic involvement in all stages; acute infection, subacute/post-infection, and growing evidence also suggests during a chronic phase, the post-acute sequalae of COVID-19 (PASC). With over 20,000 published articles on COVID and the brain at the time of writing, it is virtually impossible to present an unbiased comprehensive review of how SARS-Co-V2 impacts the nervous system. In this review, we will present an overview of common neurologic manifestations, in particular focusing on the cerebrovascular complications, and proposed pathophysiology.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Reversible Cerebral Vasoconstriction Syndrome in Patients with Coronavirus Disease: A Multicenter Case Series.

BACKGROUND AND OBJECTIVES: RCVS (Reversible Cerebral Vasoconstrictive Syndrome) is a condition associated with vasoactive agents that alter endothelial function. There is growing evidence that endothelial inflammation contributes to cerebrovascular disease in patients with coronavirus disease 2019 (COVID-19). In our study, we describe the clinical features, risk factors, and outcomes of RCVS in a multicenter case series of patients with COVID-19. MATERIALS AND METHODS: Multicenter retrospective case series. We collected clinical characteristics, imaging, and outcomes of patients with RCVS and COVID-19 identified at each participating site. RESULTS: Ten patients were identified, 7 women, ages 21 - 62 years. Risk factors included use of vasoconstrictive agents in 7 and history of migraine in 2. Presenting symptoms included thunderclap headache in 5 patients with recurrent headaches in 4. Eight were hypertensive on arrival to the hospital. Symptoms of COVID-19 included fever in 2, respiratory symptoms in 8, and gastrointestinal symptoms in 1. One patient did not have systemic COVID-19 symptoms. MRI showed subarachnoid hemorrhage in 3 cases, intraparenchymal hemorrhage in 2, acute ischemic stroke in 4, FLAIR hyperintensities in 2, and no abnormalities in 1 case. Neurovascular imaging showed focal segment irregularity and narrowing concerning for vasospasm of the left MCA in 4 cases and diffuse, multifocal narrowing of the intracranial vasculature in 6 cases. Outcomes varied, with 2 deaths, 2 remaining in the ICU, and 6 surviving to discharge with modified Rankin scale (mRS) scores of 0 (n=3), 2 (n=2), and 3 (n=1). CONCLUSIONS: Our series suggests that patients with COVID-19 may be at risk for RCVS, particularly in the setting of additional risk factors such as exposure to vasoactive agents. There was variability in the symptoms and severity of COVID-19, clinical characteristics, abnormalities on imaging, and mRS scores. However, a larger study is needed to validate a causal relationship between RCVS and COVID-19.

Admission Lymphocytopenia is Associated with Urinary Tract Infection and Nosocomial Infections in Hemorrhagic Stroke.

OBJECTIVE: Growing evidence suggests that lymphocytopenia on admission (LOA) is associated with infectious complications and poor outcomes in intracerebral hemorrhage (ICH). Whether LOA preferentially increases the risk for community acquired infections or nosocomial infections is unknown. This study investigates the relationship between LOA and nosocomial infections in a cohort of patients with ICH in a safety-net hospital. MATERIAL AND METHODS: This is a single center, observational, retrospective study of 213 patients with non-traumatic ICH admitted to the neurocritical care unit between 2008 and 2014. Patients' clinical, demographic, lab and radiologic data were retrieved from institutional electronic medical records. Nosocomial infection was defined as clinical onset 48 h after admission. RESULTS: Prevalence of LOA was 24.8%. Patients with LOA showed significant associations with mechanical ventilation (67.9% versus 49.4%; p= 0.019), higher median ICH score (2 versus 1; p=0.006), nosocomial infection (43.4% versus 28.0%; p=0.038), nosocomial UTI (24.5% versus 8.9%; p=0.003). Adjusting for baseline covariates in a multivariate logistic regression, we observed an association of LOA with nosocomial UTI (OR, 3.66 [95% CI, 1.36-9.88], p=0.010). From the Cox proportional model, patients with LOA had 1.76 times the hazard of developing of nosocomial infection, compared to those without LOA ([95% CI: 1.01, 3.07], p=0.046) and had 3.27 times the hazard of developing nosocomial UTI, compared to those without LOA ([95% CI: 1.39, 7.67], p=0.007). CONCLUSIONS: This study is the first to show that LOA is associated with nosocomial urinary tract infections and significantly shorter times to develop nosocomial infections.

Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.