Clinical Utilization of the FilmArray Meningitis/Encephalitis (ME) Multiplex Polymerase Chain Reaction (PCR) Assay.

Objective: To assess the clinical utilization and performance of the FilmArray® Meningitis/Encephalitis (ME) multiplex polymerase chain reaction (PCR) panel in a hospital setting. Background: Rapid diagnosis and treatment of central nervous system (CNS) infections are critical to reduce morbidity and mortality. The ME panel is a Food and Drug Administration (FDA) approved rapid multiplex PCR assay that targets 14 bacteria, viruses, and fungi. Previous studies show an overall agreement of 93-99% between the ME panel and conventional diagnostic testing. However, few studies have evaluated the clinical implementation of the ME assay, which is available for routine use at our institution. Methods: We performed a single center retrospective chart review of inpatients who underwent ME panel testing from August 2016 to May 2017. Clinical, radiologic, and laboratory data were reviewed to determine the clinical significance of results. Indication for lumbar puncture (LP), time to results of the ME panel, and duration of antimicrobial therapy were evaluated. Results: Seven hundred and five inpatients underwent ME testing, of whom 480 (68.1%) had clinical suspicion for CNS infection with 416 (59.0%) receiving empiric antimicrobial treatment for CNS infection. The median time-to-result of the ME panel was 1.5 h (IQR, 1.4-1.7). Overall agreement between the ME panel results and clinico-laboratory assessment was 98.2%. Forty-five patients tested positive by ME, of which 12 (26.6%) were determined likely to be clinically insignificant. Conclusions: Routine availability of the ME panel led to overutilization of diagnostic test ordering, as demonstrated by the fact that over one-third of ME panel tests performed were ordered for patients with little or no suspicion for CNS infection. The median time from LP to ME panel result was 1.5 h (IQR, 1.4-1.7). The ME panel's rapid turn-around time contributed to the overuse of the test. Approximately one-quarter of positive ME results were deemed clinically insignificant, though the impact of these positive results requires additional evaluation. Twenty-four and forty-eight hours after the ME panel resulted, 68 and 25% of patients started on empiric therapy remained on antibiotics, respectively. The median time from diagnosis to discontinuation and/or narrowing of antibiotic coverage was 25.6 h (IQR, 3.6-42.5). Further consideration of the appropriate indications for use of the ME panel in clinical settings is required.

Zika Virus and Neurologic Disease.

Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family. Although most cases are mild or go undetected, rare severe neurologic effects, including congenital ZIKV syndrome (CZS) and Guillain-Barré syndrome, have been identified. The serious neurologic complications associated with ZIKV prompted the declaration of the public health emergency of international concern by the World Health Organization. Overall, transmission occurred throughout South and Central America as well as the Caribbean, affecting 48 countries and territories from March 2015 to March 2017. Long-term management of CZS requires a comprehensive combination of supportive services throughout early development.

Nervous System Infections and the Global Traveler.

Neurological complications of infectious diseases are associated with high rates of morbidity and mortality. It is imperative that neurologists be up-to-date on current developments including typical and atypical presentations of neurological infections in travelers, diagnostic and treatment recommendations, and emerging pathogen resistance patterns to avoid fatal outcomes and long-term sequelae. This article will address concepts of emerging and reemerging infectious diseases, and will provide updates on the neurological manifestations of select emerging and reemerging infections, including Ebola virus, bacterial meningitis, enterovirus 71, Zika virus, cerebral malaria, and Japanese encephalitis. Emerging and reemerging neurotropic infectious diseases, including Zika virus, have recently been major global health threats. Factors contributing to the emergence of infectious diseases include closer contact with zoonoses, population growth in cities, globalization, environmental changes, and the rise in antibiotic resistance. Serotype replacement of bacterial meningitis, the possibility of viral persistence in the central nervous system in Ebola virus, antibiotic resistance of malaria, and the evolution of neurovirulent strains of Zika virus display some of the developing challenges that accompany various neurotropic infectious diseases. Neurologists should be aware of the factors contributing to the emergence and reemergence of neurotropic infectious diseases. As emerging and reemerging neurotropic infectious continue to be a major global health security threat, clinicians should be aware of the risks to travelers and current guidelines on prevention and management.

Potential Clinical Value of Multiparametric PET in the Prediction of Alzheimer's Disease Progression.

OBJECTIVE: To evaluate the potential clinical value of quantitative functional FDG PET and pathological amyloid-ß PET with cerebrospinal fluid (CSF) biomarkers and clinical assessments in the prediction of Alzheimer's disease (AD) progression. METHODS: We studied 82 subjects for up to 96 months (median = 84 months) in a longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) project. All preprocessed PET images were spatially normalized to standard Montreal Neurologic Institute space. Regions of interest (ROI) were defined on MRI template, and standard uptake values ratios (SUVRs) to the cerebellum for FDG and amyloid-ß PET were calculated. Predictive values of single and multiparametric PET biomarkers with and without clinical assessments and CSF biomarkers for AD progression were evaluated using receiver operating characteristic (ROC) analysis and logistic regression model. RESULTS: The posterior precuneus and cingulate SUVRs were identified for both FDG and amyloid-ß PET in predicating progression in normal controls (NCs) and subjects with mild cognitive impairment (MCI). FDG parietal and lateral temporal SUVRs were suggested for monitoring NCs and MCI group progression, respectively. 18F-AV45 global cortex attained (78.6%, 74.5%, 75.4%) (sensitivity, specificity, accuracy) in predicting NC progression, which is comparable to the 11C-PiB global cortex SUVR's in predicting MCI to AD. A logistic regression model to combine FDG parietal and posterior precuneus SUVR and Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Total Mod was identified in predicating NC progression with (80.0%, 94.9%, 93.9%) (sensitivity, specificity, accuracy). The selected model including FDG posterior cingulate SUVR, ADAS-Cog Total Mod, and Mini-Mental State Exam (MMSE) scores for predicating MCI to AD attained (96.4%, 81.2%, 83.6%) (sensitivity, specificity, accuracy). 11C-PiB medial temporal SUVR with MMSE significantly increased 11C-PiB PET AUC to 0.915 (p<0.05) in predicating MCI to AD with (77.8%, 90.4%, 88.5%) (sensitivity, specificity, accuracy). CONCLUSION: Quantitative FDG and 11C-PiB PET with clinical cognitive assessments significantly improved accuracy in the predication of AD progression.