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Introduction: Encephalitis presents with high morbidity and mortality in both HIV-infected and HIV-negative patients. There are currently no studies comparing HIV-infected and HIV-negative patients admitted to the hospital with acute encephalitis. Methods: We conducted a multicenter, retrospective study of adults admitted to the hospital with a diagnosis of encephalitis in Houston, Texas between 2005 and 2020. We describe the clinical manifestations, etiology, and outcomes of these patients with a focus on those infected with HIV. Results: We identified 260 patients with encephalitis, 40 of whom were infected with HIV. Viral etiology was identified in 18 of the 40 HIV-infected patients (45.0%); bacterial in 9 (22.5%); parasitic in 5 (12.5%); fungal in 3 (7.5%); immune-mediated in 2 (5.0%). Eleven cases had unclear etiology (27.5%). More than one disease process was identified in 12 (30.0%) patients. HIV-infected persons were more likely to have neurosyphilis (8/40 vs. 1/220; OR 55; 95%CI 6.6–450), CMV encephalitis [5/18 vs. 1/30; OR 11.2 (1.18–105)], or VZV encephalitis (8/21 vs. 10/89; OR 4.82; 1.62–14.6) compared to the HIV-negative patients. Inpatient mortality was similar in the HIV-infected and HIV-negative patients, 15.0% vs 9.5% [p = 0.4, OR 1.67 (0.63–4.44)], but one-year mortality was higher for the HIV-infected patients, 31.3% vs 16.0% [p = 0.04, OR 2.40 (1.02–5.55)]. Conclusion: This large, multicenter study shows that HIV-infected patients with encephalitis have a distinct pattern of disease when compared with HIV-negative patients, and that this population has nearly twice the odds of mortality in the year following hospitalization. [ABSTRACT FROM AUTHOR]

Background: Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE. Methods: We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1. Results: We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown. Conclusions: Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit. [ABSTRACT FROM AUTHOR]

The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC polyomavirus (JCPyV) PCR in CSF does not always rule out JCPyV-related PML. In this narrative review, we sought to examine the characteristic of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and provide alternative approaches in this scenario. [ABSTRACT FROM AUTHOR]

Creativity can help people to innovate, overcome obstacles, and successfully navigate challenges in daily life. Some aspects of creativity rely on the prefrontostriatal loops and executive functions, which can be compromised in persons with HIV (PWH). This pilot study examined whether neuropsychological functioning plays a role in creativity in PWH. A consecutive series of 41 PWH who were referred to an urban neuropsychology clinic in southeastern Texas were enrolled. Participants completed the Abbreviated Torrance Test for Adults (ATTA) to measure creativity, from which standardized creativity scores of fluency, originality, elaboration, and flexibility were derived. Participants also completed several measures of everyday functioning and a brief clinical neuropsychological battery measuring executive functions, motor skills, memory, and visuoconstruction. Global neuropsychological functioning showed a large, positive association with ATTA creativity performance that did not vary meaningfully by creativity domain and was independent of premorbid IQ. ATTA creativity scores were not associated with any measure of everyday functioning. Findings from this pilot study suggest that higher levels of neuropsychological functioning may support multiple dimensions of creativity in adults with HIV disease. Future studies might examine whether creativity moderates the association between HIV-associated neurocognitive impairment and various health behaviors (e.g., adherence, appointment attendance). [ABSTRACT FROM AUTHOR]

Background: International guidelines exist for obtaining a head computed tomography (CT) scan before a lumbar puncture (LP) in adults with suspected meningitis but there are no studies comparing them in their ability to identify intracranial abnormalities. Methods: A retrospective study of 202 cases of adults with community-acquired bacterial meningitis at 16 hospitals in Houston from December 2004 until May 2019 to compare the 4 guidelines' ability in identifying minor and major intracranial findings, cases in which CT findings changed management, and patients who suffered cerebral herniation. Results: Minor and major intracranial findings were seen in 69 (34.1%) and in 24 (11.8%) of the patients, respectively. A total of nine (37.5%) of the major intracranial findings prompted a neurosurgical intervention. A total of four (1.9%) patients had cerebral herniation. The Infectious Diseases of America (IDSA), the United Kingdom (UK), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and the Swedish guidelines for cranial imaging were met in 92.1%, 54%, 41.6%, and in 23.3% of the patients, respectively. The IDSA, UK, European, and the Swedish guidelines missed 0%, 20.8%, 41.7%, and 70.8% of the major intracranial findings and 0, 1, 3 and 4 of the 9 patients that prompted a neurosurgical intervention, respectively. All four patients with cerebral herniation met the criteria for all four guidelines. Conclusion: Out of the four international guidelines, only the IDSA recommendations for cranial imaging did not miss any major intracranial abnormality or any finding that prompted a neurosurgical intervention but all guidelines identified herniation. [ABSTRACT FROM AUTHOR]

Objective: Adjuvant steroids have been used for the treatment of encephalitis, although there is limited data regarding its benefit. We described the use and impact of adjunctive steroids on adverse clinical outcomes (ACO) in adults with encephalitis. Methods: Retrospective observational study of 230 adults with encephalitis at two tertiary care hospital systems in Houston, Texas, between August 2008 and September 2017. An ACO was assessed at the time of death or discharge and defined as a Glasgow Outcome Scale 1–4. A propensity score analysis was performed. Results: Out of 230 adult encephalitis patients enrolled, 121 (52.6%) received steroids. Adjunctive steroids were given more frequently to those who had focal neurological deficits (P = 0.01), required mechanical ventilation (MV) (P = 0.01), had intensive care unit admission (P < 0.001), had white matter abnormalities (P = 0.01) or cerebral edema on magnetic resonance imaging of the brain (P = 0.003). An ACO was seen in 135 (58.7%) of patients. The use of adjunctive steroids did not impact ACOs (P = 0.52) on univariate analyses or after propensity score matching. Predictors for an ACO in logistic regression analyses included a Glasgow Coma Score (GCS) < 8, fever, MV, and cerebral edema. Interpretation: Adjunctive steroids are used more frequently in sicker patients and are not associated with improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Healthcare-associated ventriculitis and meningitis (HCAVM) is associated with adverse clinical outcomes in the majority of patients [[1]-[3]]. Interestingly, patients with Gram-positive HCAVM had higher proportion of having a positive nasal MRSA PCR screen ( I p i = 0.007). HCAVM remains associated with adverse outcomes in the majority of patients and even though patients with Gram-negative HCAVM are sicker than those with Gram-positive infections, outcomes are the same. [Extracted from the article]

Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279–2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454–0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142–23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046–5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216–0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037–0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Many patients with suspected meningitis do not require hospitalization yet are admitted, often resulting in unnecessary care and additional cost. We assessed the possible economic impact of a rapid multiplex test for suspected adult community-acquired meningitis/encephalitis. Methods: A model simulated diagnosis, clinical decisions, resource use/costs of standard of care (SOC) and two cerebrospinal fluid (CSF) testing strategies using the FDA-cleared BioFire® FilmArray® System (FA) which provides results in approximately one hour. Results: Pathogens detected by FA caused approximately 74% of cases, 97% of which would be accurately diagnosed with FA. False positives and false negatives more often led to extended/unnecessary admission than inappropriate discharge/missed admission. Mean cost per case ranged from 16829 to 20791. A strategy of testing all suspected cases yielded greater savings (2213/case) than testing only those with abnormal CSF (812/case) and both were less expensive than SOC. Conclusion: This economic analysis demonstrates that FA can inform more appropriate clinician decisions resulting in cost savings with greater economic benefits achievable with syndromic testing of all cases, rather than SOC or targeted syndromic testing. [ABSTRACT FROM AUTHOR]

Antimicrobials are a widely used class of medications, but several of them are associated with neurological and psychiatric side effects. The exact incidence of neurotoxicity with anti-infectives is unknown, although it is estimated to be < 1%. Neurotoxicity occurs with all classes of antimicrobials, such as antibiotics, antimycobacterials, antivirals, antifungals and antiretrovirals, with side effects ranging from headaches, anxiety and depression to confusion, delirium, psychosis, mania and seizures, among others. It is important to consider these possible side effects to prevent misdiagnosis or delayed treatment as drug withdrawal can be associated with reversibility in most cases. This article highlights the different neurotoxic effects of a range of antimicrobials, discusses proposed mechanisms of onset and offers general management recommendations. The effects of antibiotics on the gut microbiome and how they may ultimately affect cognition is also briefly examined. [ABSTRACT FROM AUTHOR]

The current prospective observational study evaluated the impact of baseline neurocognitive impairment on future viral load suppression among antiretroviral medication naive persons newly diagnosed with HIV infection. We used the Montreal Cognitive Assessment (MoCA) score less than 26, to identify patients with neurocognitive deficits. Of the 138 patients enrolled; virologic suppression was seen in 61% of the participants, while 72% of the participants had a MoCA score less than 26 at baseline. Variables significantly associated with low MoCA score included higher age (p < 0.01) and presence of depression (p < 0.01). After adjusting for these variables, MoCA score less than 26 was significantly associated with a higher risk of failing achieve viral load suppression (adjusted OR 2.7; 95% CI 1.09-6.69). Baseline neurocognitive deficit as measured by MoCA was associated with a higher risk for failing to achieve viral load suppression at one-year follow-up. [ABSTRACT FROM AUTHOR]

West Nile Virus (WNV) can be a neuroinvasive pathogen that may produce persistent mild-to-moderate neurocognitive impairments in some infected persons. Intra-individual variability (IIV) is an index of a person’s performance across a neuropsychological test or battery, which is an indicator of neurocognitive control and integrity of prefrontal systems. The present study examined possible associations of IIV to neurological health and well-being in WNV infection. Participants included 84 adults with a range of clinical WNV disease (31 West Nile Encephalitis, 16 West Nile Meningitis, 37 West Nile Fever) who completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). IIV was operationalized as covariance of variation (CoV), or the intra-individual standard deviation across 5 age-adjusted RBANS standard scores divided by the mean of standard scores. Participants were assessed for health-related quality of life (QoL) using the RAND 36-item short form health survey (SF-36). Analyses revealed that the West Nile Encephalitis group had higher neurocognitive CoV compared to the West Nile Fever group, and this difference was associated with a medium effect size (Cohen’s d = .52). Mixed linear models controlling for estimated IQ, activities of daily living, depression, neuroinvasive disease groups, and fatigue showed that higher RBANS CoV was associated with lower physical, but not mental health QoL. In persons with WNV infection, there is a modest association between elevations in IIV and encephalitis, and even subtle disruptions in neuropsychological functioning show relationships with important self-reported functioning as measured by physical health quality of life. Future studies should examine whether IIV predicts long-term health outcomes (e.g., mortality) in individuals infected with WNV. [ABSTRACT FROM AUTHOR]

Case description: A 38-year-old man presented with headaches and generalized weakness. He was found to have AIDS; a ring-enhancing central nervous system lesion was found on brain imaging and he had elevated serum Toxoplasma gondii IgG levels. A diagnosis of presumptive toxoplasma encephalitis was made and he received antiretrovirals and antitoxoplasma therapy for 4 years. Intermittent headaches and evidence of disease progression on neuroimaging warranted further evaluation and cerebrospinal fluid analysis revealed amebic forms on hematoxylin and eosin staining and positive polymerase chain reaction testing for Acanthamoeba spp. He was placed on miltefosine, fluconazole, trimethoprim-sulfamethoxazole and flucytosine for 7 months. Five months after therapy discontinuation he remains asymptomatic and is taking only antiretroviral therapy. Conclusion: This is the first report of a patient with AIDS and granulomatous amebic encephalitis who survived with medical therapy only. [ABSTRACT FROM AUTHOR]

Nosocomial meningitis can occur in association with central nervous system (CNS) devices such as cerebrospinal shunts or drains, intrathecal pumps, and deep brain stimulators and carry substantial morbidity and mortality. Diagnosing and treating these infections may be challenging to physicians as cerebrospinal fluid cultures may be negative due to previous antibiotic therapy and cerebrospinal abnormalities may be secondary to the primary neurosurgical issue that prompted the placement of the CNS device (e.g., 'chemical meningitis' due to intracranial hemorrhage). Besides antibiotic therapy given intravenously and sometimes intrathecally, removal of the device with repeat cultures prior to re-implantation is key in achieving successful outcomes. [ABSTRACT FROM AUTHOR]

Objective: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. Methods: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. Results: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3-2.7, p = 0.0001) were associated with diffuse inflammation. Conclusions: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses. [ABSTRACT FROM AUTHOR]

Objectives: To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections. Methods: Retrospective review of adult patients with positive HSV or VZV polymerase chain reaction on CSF from an observational study of meningitis or encephalitis in Houston, TX (2004-2014), and New Orleans, LA (1999-2008). Results: Ninety-eight adults patients were identified; 25 had encephalitis [20 (20.4 %) HSV, 5 (5.1 %) VZV], and 73 had meningitis [60 (61.1 %) HSV and 13 (13.3 %) VZV]. HSV and VZV had similar presentations except for nausea ( P < 0.01) and rash ( P < 0.001). The CSF profile did not differ between HSV and VZV infection. Abnormal neuroimaging findings were found in 11.6 % (10/86) brain CTs and 21.3 % (16/75) brain MRIs. The EEG was abnormal in 57.9 % (11/19). Sixteen patients (16.3 %) had an ACO (10 HSV encephalitis, 3 VZV encephalitis and 3 VZV meningitis). Intravenous acyclovir administered within 48 h was protective against an ACO [OR 0.19 (0.04-0.80), P = 0.02). However, on logistic regression only Charlson comorbidity score >1 and an encephalitis presentation were independently associated with an ACO. The treatment for HSV meningitis was variable, and all patients had a good clinical outcome. Conclusion: Alpha herpes CNS infections due to HSV and VZV infections have similar clinical and laboratory manifestations. ACO was observed more frequently in those patients with comorbidities and an encephalitis presentation. [ABSTRACT FROM AUTHOR]

The extensive use of fluconazole in the previous two decades has fostered the emergence of azole-resistant strains, including non- albicans species such as C. glabrata. The main mechanisms of fluconazole resistance described involve alteration of the quality or quantity of 14-alpha-demethylase enzyme or reduced access of the drug to the target enzyme by upregulation of efflux pumps. Fluconazole prophylaxis has been used successfully to prevent fungal infections in high-risk neonates, neutropenic patients, individuals with HIV infection, recipients of solid organ (eg, liver) transplants and bone marrow transplants, and patients in intensive care units, with a small increase in the risk of colonization, but not infection, with fluconazole-resistant Candida isolates. Among other risk factors, recent fluconazole exposure is associated with fluconazole-resistant candidemia. [ABSTRACT FROM AUTHOR]

Immunization against the most common meningeal pathogens is the leading factor associated with decreased incidence of bacterial meningitis in countries where routine vaccination is available. This is most dramatically illustrated by the reduction in the incidence of Haemophilus influenzae type b meningitis. The incidence of bacterial meningitis has decreased by 55% since the introduction of the H. influenzae type b conjugate vaccine in 1990. H. influenzae occurred primarily in children younger than 5 years of age, and so the median age of patients with bacterial meningitis has now increased to 39 years of age in the United States, and the leading pathogen is currently Streptococcus pneumoniae. Three other control measures (ie, universal screening and antibiotic prophylaxis of pregnant women for Group B streptococci and the implementation and availability of the S. pneumoniae and Neisseria meningitidis conjugate vaccines) have likely further decreased the incidence of these meningeal pathogens. Lastly, the worldwide emergence of multidrug-resistant pneumococci has complicated the empiric therapy of bacterial meningitis. [ABSTRACT FROM AUTHOR]

The aseptic meningitis syndrome (AMS) is as a diagnostic and management challenge. Since the initial description of AMS in 1925, the differential diagnosis of infectious and noninfectious agents associated with this syndrome has progressed. Although most cases of aseptic meningitis have a benign outcome, several etiologies require urgent therapy if the patient is to survive and be cured. This review will address the differential diagnosis of AMS and focus on recent empiric data that may aid the clinician treating these patients. [ABSTRACT FROM AUTHOR]

Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.