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There have been several major advances in therapeutic options for the treatment of neurological infections over the past two decades. These advances encompass both the development of new antimicrobial therapies and the repurposing of existing agents for new indications. In addition, advances in our understanding of the host immune response have allowed for the development of new immunomodulatory strategies in the treatment of neurological infections. This review focuses on the key advances in the treatment of neurological infections, including viral, bacterial, fungal, and prion diseases, with a particular focus on immunomodulatory treatment options. This review also highlights the process by which clinicians can request access to therapeutic agents on a compassionate or emergency basis when they may not be commercially available. While many therapeutic advances have been achieved in the past several years, there remains a pressing need for the continued development of additional therapeutic agents in the treatment of neurological infections.

Neuroinfectious diseases represent a growing threat to public health globally. Infections of the central nervous system remain challenging to diagnose and treat, partially driven by the fact that a high proportion of emerging pathogens are capable of causing neurological disease. Many of the trends driving the emergence of novel pathogens, including climate change, ecological degradation, urbanization, and global travel, have accelerated in recent years. These circumstances raise concern for the potential emergence of additional pathogens of pandemic potential in the coming years, necessitating a stronger understanding of the forces that give rise to the emergence and spread of neuroinvasive pathogens and a commitment to public health infrastructure to identify and treat these diseases. In this review, we discuss the clinical and epidemiological features of three types of emerging neuroinvasive pathogens of significant public health consequences that are emblematic of key ongoing trends in global health. We first discuss dengue viruses in the context of climate change, considering the environmental factors that allow for the expansion of the geographic range and seasonal population of the viruses’ vector. We then review the rising prevalence of fungal meningitis secondary to medical tourism, a trend representative of the highly globalized nature of modern healthcare. Lastly, we discuss the increasing prevalence of antibiotic-resistant neurological infections driven by the intersection of antibiotic overuse in medical and agricultural settings. Taken together, the rising prevalence of these conditions necessitates a recommitment to investment in public health infrastructure focused on local and global infectious disease surveillance coupled with ongoing development of novel therapeutics and vaccines for emerging pathogens. Such emerging threats also obviate the need to address the root causes driving the emergence of novel infectious diseases, including a sustained effort to address anthropogenic climate change and environmental degradation.

Background: Children with tuberculous meningitis (TBM) present with diagnostic challenges as they often have atypical clinical features. Objective: To describe the baseline characteristic features of children diagnosed with central nervous system (CNS) TB (TBM and tuberculoma). Design: Retrospective descriptive study. Methods: Children less than 12 years presenting with neurological signs and symptoms were assessed for a therapeutic TBM trial eligibility. The results of their clinical, laboratory, neuroimaging, cerebrospinal fluid evaluations were analysed for TBM diagnosis. Results: Of 600 children evaluated, 61(10%) had CNS tuberculosis; TBM 47, tuberculoma 14. 20(33%) had definite TBM. Mean age of children with TBM was 5 ± 3.4 years. Of 47, 13(28%), 21(45%) and 13(28%) had grade I, II, and III disease respectively. Abnormalities suggestive of TBM in MRI and computed tomography brain were observed in 76% (26/34) and 77% (24/31) respectively. Abnormal cerebrospinal fluid white blood cell count, protein and glucose were observed in 56% (24/43), 49% (22/45), 47% (21/45) respectively. Among 41 patients with TBM followed up until discharge, five died. Conclusion: Younger children with TBM have severe forms. Confirmatory results may not be available in all. A holistic approach to care including addressing complications of hydrocephalus and strokes is needed.

Abstract Objective Emerging variants and sublineages of SARS‐CoV‐2 have differing disease severity, transmissibility, and immune evasion. The neurological conditions associated with the original strain of SARS‐CoV‐2 are well established. Our study assessed the neurological presentations specific to hospitalized patients during the B.1.1.529 (Omicron) variant surge in New York City. Methods A total of 178 cases with positive RT‐PCR result within 6 weeks before admission, and subsequent development of select neurological conditions during the SARS‐CoV‐2 B.1.1.529 (Omicron) surge between December 1, 2021 and February 28, 2022, were included from 12,800 SARS‐CoV‐2‐positive hospital admissions. Clinical data from acute hospitalizations were compared to findings of inpatient neurological cases with COVID‐19 infections from the initial surge in NYC in the same hospital system. Results Compared to SARS‐CoV‐2 infections of the original strain, COVID‐19 cases hospitalized during the Omicron surge (B.1.1.529) were associated with incidental and/or asymptomatic COVID‐19 cases (96, 53.9%) and an increased incidence of pre‐existing neurological and immunocompromising conditions. Encephalopathy, seizures, and stroke remained the most prevalent neurological conditions identified in hospitalized COVID‐19 cases during the study period, reflecting a similar distribution of neurological presentations associated with the original strain. Interpretation In our cohort of 178 admitted SARS‐CoV‐2‐positive patients with select neurological conditions during the Omicron B.1.1.529 surge, 54% of COVID‐19 cases were considered incidental and/or asymptomatic, and the identified neurological conditions resembled those associated with the original SARS‐CoV‐2 strain. Further studies characterizing neurological presentation in Omicron sublineages and other variants are warranted in an ongoing COVID‐19 pandemic.

West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the clinical and diagnostic features of WNND cases at two major academic medical centers in New York City in routine clinical practice. We retrospectively reviewed the charts of thirty-six patients with WNND, including twenty-six encephalitis, four meningitis, and six AFP cases. The most common presenting symptoms were fever (86.1%) and gastrointestinal symptoms (38.9%) in addition to altered mental status (72.2%), lethargy (63.9%), gait disturbances (46.2%), and headache (44.4%). Fourteen (48.3%) patients displayed acute magnetic resonance imaging (MRI) findings, particularly T2 hyperintensities in the bilateral thalami, brainstem, and deep white matter. New York State Department of Health WNV CSF IgM testing was utilized for diagnosis in 58.3% of patients; however, just 38.1% had the result by discharge, compared to 85.6% of those who underwent serum IgM testing. The median length of stay was 13.5 days, 38.9% were intubated, and three patients (8.9%) died during acute hospitalization. Our findings underscore the morbidity, mortality, and diagnostic challenges of WNND, suggesting the potential utility of serum IgM testing in combination with confirmatory CSF testing to expedite diagnosis in the acute setting.

Dominant missense mutations in RanBP2/Nup358 cause Acute Necrotizing Encephalopathy (ANE), a pediatric disease where seemingly healthy individuals develop a cytokine storm that is restricted to the central nervous system in response to viral infection. Untreated, this condition leads to seizures, coma, long-term neurological damage and a high rate of mortality. The exact mechanism by which RanBP2 mutations contribute to the development of ANE remains elusive. In November 2021, a number of clinicians and basic scientists presented their work on this disease and on the interactions between RanBP2/Nup358, viral infections, the innate immune response and other cellular processes.

Abstract Objectives Early presentation and workup for acute infectious (IE) and autoimmune encephalitis (AE) are similar. This study aims to identify routine laboratory markers at presentation that are associated with IE or AE. Methods This was a multi‐center retrospective study at three tertiary care hospitals in New York City analyzing demographic and clinical data from patients diagnosed with definitive encephalitis based on a confirmed pathogen and/or autoantibody and established criteria for clinical syndromes. Results Three hundred and thirty‐three individuals with confirmed acute meningoencephalitis were included. An infectious‐nonbacterial (NB) pathogen was identified in 151/333 (45.40%), bacterial pathogen in 95/333 (28.50%), and autoantibody in 87/333 (26.10%). NB encephalitis was differentiated from AE by the presence of fever (NB 62.25%, AE 24.10%; p 1:40; NB 11.54%, AE 32.73%; p

Neurocysticercosis (NCC), the infection of the central nervous system caused by Taenia solium larvae (cysticerci), is a major cause of acquired epilepsy worldwide. Calcification in NCC is the most common neuroimaging finding among individuals with epilepsy in T. solium-endemic areas. We describe the demographic, clinical, and radiological profiles of a large hospital cohort of patients with calcified NCC in Peru (during the period 2012–2022) and compared profiles between patients with and without a previous known diagnosis of viable infection. A total of 524 patients were enrolled (mean age at enrollment: 40.2 ± 15.2 years, mean age at symptom onset: 29.1 ± 16.1 years, 56.3% women). Of those, 415 patients (79.2%) had previous seizures (median time with seizures: 5 years, interquartile range (IQR): 2–13 years; median number of seizures: 7 (IQR: 3–32)), of which 333 (80.2%) had predominantly focal to bilateral tonic-clonic seizures; and 358 (68.3%) used antiseizure medication). Patients had a median number of three calcifications (IQR: 1–7), mostly located in the frontal lobes (79%). In 282 patients (53.8%) there was a previous diagnosis of viable infection, while 242 only had evidence of calcified NCC since their initial neuroimaging. Most patients previously diagnosed with viable infection were male, had previous seizures, had seizures for a longer time, had more calcifications, and had a history of taeniasis more frequently than patients without previously diagnosed viable infection (all p < 0.05). Patients with calcified NCC were heterogeneous regarding burden of infection and clinical manifestations, and individuals who were diagnosed after parasites calcified presented with milder disease manifestations.

BackgroundFor patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) and ovarian teratoma, “conservative” surgical approaches (complete or partial unilateral oophorectomy or bilateral partial oophorectomies) are associated with clinical improvement. “Aggressive” ovarian resections (complete bilateral oophorectomy or “blind” ovarian resections without pre-operative evidence of teratoma) are also reported, although the evidence supporting these approaches is unclear.ObjectiveTo compare the one-year functional outcomes of patients with NMDARE who underwent conservative vs. aggressive ovarian resections.MethodsPatients with NMDARE undergoing ovarian resection between January 1st, 2012 and December 31st, 2021 were retrospectively identified from three North American tertiary care centers. Primary outcome was a modified Rankin Scale score of 0–2 one year after ovarian resection. Fisher exact and Wilcoxon rank sum tests were used to compare demographic features, disease characteristics, and functional outcomes between the two surgical groups. A fixed-effects meta-analysis of studies reporting functional outcomes based on surgical approach was also performed.ResultsTwenty-three patients were included. Eight underwent aggressive surgical management. There was a non-significant trend toward an association between aggressive surgical management and younger age-at-onset, higher baseline disease severity, and longer delays to treatment. There was no difference between “aggressive” (3/8, 38%) and “conservative” (11/15, 73%) management groups in achieving the primary outcome (OR95% =

The COVID-19 pandemic has shed light on the challenges we face as a global society in preventing and containing emerging and re-emerging pathogens. Multiple intersecting factors, including environmental changes, host immunological factors, and pathogen dynamics, are intimately connected to the emergence and re-emergence of communicable diseases. There is a large and expanding list of communicable diseases that can cause neurological damage, either through direct or indirect routes. Novel pathogens of neurotropic potential have been identified through advanced diagnostic techniques, including metagenomic next-generation sequencing, but there are also known pathogens which have expanded their geographic distribution to infect non-immune individuals. Factors including population growth, climate change, the increase in animal and human interface, and an increase in international travel and trade are contributing to the expansion of emerging and re-emerging pathogens. Challenges exist around antimicrobial misuse giving rise to antimicrobial-resistant infectious neurotropic organisms and increased susceptibility to infection related to the expanded use of immunomodulatory treatments. In this article, we will review key concepts around emerging and re-emerging pathogens and discuss factors associated with neurotropism and neuroinvasion. We highlight several neurotropic pathogens of interest, including West Nile virus (WNV), Zika Virus, Japanese Encephalitis Virus (JEV), and Tick-Borne Encephalitis Virus (TBEV). We emphasize neuroinfectious diseases which impact the central nervous system (CNS) and focus on flaviviruses, a group of vector-borne pathogens that have expanded globally in recent years and have proven capable of widespread outbreak.

Abstract Objective To report initial results of a planned multicenter year‐long prospective study examining the risk and impact of COVID‐19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS). Methods In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVID‐19 in persons with NID (PwNID) and change in their neurological care. Results Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020. 202 (18%) participants, residing in areas with high COVID‐19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID‐19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID‐19 were younger, more racially diverse, and reported more depression and liver disease. PwNID had the same rate of suspected COVID‐19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of PwNID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID‐19 (ORadj = 1.45, 1.17–1.84). Interpretations Our study of real‐time, patient‐reported experience during the COVID‐19 pandemic complements physician‐reported MS case registries which capture an excess of severe cases. Overall, PwNID seem to have a risk of suspected COVID‐19 similar to the reference population.

Abstract Background We sought to identify perceptions of neurorehabilitation challenges for paediatric cerebral malaria (CM) survivors post-hospital discharge at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. Methods An exploratory approach was used to qualitatively investigate the perceived neurorehabilitation challenges for paediatric CM survivors. Data were collected through semi-structured in-depth interviews (IDIs) and focus group discussions (FGDs). Eighteen data-gathering sessions were conducted with 38 total participants, including 3 FGDs with 23 primary caregivers, 11 IDIs with healthcare workers at QECH, and 4 IDIs with community-based rehabilitation workers (CRWs). Results FGDs revealed that caregivers lack important knowledge about CM and fear recurrence of CM in their children. Post-CM children and families experience substantial stigma and sociocultural barriers to integrating into their community and accessing neurorehabilitative care. At a community-level, rehabilitation infrastructure, including trained staff, equipment, and programmes, is extremely limited. Rehabilitation services are inequitably accessible, and community-based rehabilitation remains largely unavailable. Conclusions There is an urgent need to establish further training of rehabilitation personnel at all levels and to build accessible rehabilitation infrastructure in Malawi for post-CM patients. Additional work is required to expand this study across multiple regions for a holistic understanding of neurorehabilitation needs.

Abstract We document the neuropathologic findings of a 73-year old man who died from acute cerebellar hemorrhage in the context of relatively mild SARS-CoV2 infection. The patient developed sudden onset of headache, nausea, and vomiting, immediately followed by loss of consciousness on the day of admission. Emergency medical services found him severely hypoxemic at home, and the patient suffered a cardiac arrest during transport to the emergency department. The emergency team achieved return of spontaneous circulation after over 17 min of resuscitation. A chest radiograph revealed hazy bilateral opacities; and real-time-PCR for SARS-CoV-2 on the nasopharyngeal swab was positive. Computed tomography of the head showed a large right cerebellar hemorrhage, with tonsillar herniation and intraventricular hemorrhage. One day after presentation, he was transitioned to comfort care and died shortly after palliative extubation. Autopsy performed 3 h after death showed cerebellar hemorrhage and acute infarcts in the dorsal pons and medulla. Remarkably, there were microglial nodules and neuronophagia bilaterally in the inferior olives and multifocally in the cerebellar dentate nuclei. This constellation of findings has not been reported thus far in the context of SARS-CoV-2 infection.

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

Objective: There is considerable uncertainty regarding the optimal use of rifampicin for the treatment of tuberculous (TB) meningitis. A pharmacokinetic modeling and simulation study of rifampicin concentrations in cerebrospinal fluid (CSF) during TB meningitis treatment was performed in this study. Methods: Parameters for rifampicin pharmacokinetics in CSF were estimated using individual-level rifampicin pharmacokinetic data, and the model was externally validated in three separate patient cohorts. Monte Carlo simulations of rifampicin serum and CSF concentrations were performed. The area under the rifampicin CSF concentration-versus-time curve during 24 h (AUC0–24) relative to the minimum inhibitory concentration (MIC) served as the pharmacodynamic target. Results: Across all simulated patients on the first treatment day, 85% attained the target AUC0–24/MIC ratio of 30 under a weight-based dosing scheme approximating 10 mg/kg. At the rifampicin MIC of 0.5 mg/l, the probability of AUC0–24/MIC target attainment was 26%. With an intensified dosing strategy corresponding to 20 mg/kg, target attainment increased to 99%, including 93% with a MIC of 0.5 mg/l. Conclusions: Under standard dosing guidelines, few TB meningitis patients would be expected to attain therapeutic rifampicin exposures in CSF when the MIC is ≥0.5 mg/l. Either downward adjustment of the rifampicin MIC breakpoint in the context of TB meningitis, or intensified rifampicin dosing upwards of 20 mg/kg/day, would reflect the likelihood of pharmacodynamic target attainment in CSF. Keywords: Tuberculosis, Meningitis, Tuberculous meningitis, Pharmacokinetics, Pharmacodynamics

Critical illness and sepsis are commonly associated with subclinical seizures. COVID-19 frequently causes severe critical illness, but the incidence of electrographic seizures in patients with COVID-19 has been reported to be low. This retrospective case series assessed the incidence of and risks for electrographic seizures in patients hospitalized with COVID-19 who underwent continuous video electroencephalography monitoring (cvEEG) between March 1st, 2020 and June 30th, 2020. One hundred and twenty-two patients were initially identified who resulted SARS-CoV-2 nasopharyngeal RT-PCR swab positivity with any electroencephalography order placed in the EMR. Seventy-nine patients met study inclusion criteria: age ≥18 years, >1 h of cvEEG monitoring, and positive SARS-CoV-2 nasopharyngeal swab PCR. Six (8%) of the 79 patients suffered electrographic seizures (ES), three of whom suffered non-convulsive status epilepticus. Acute hyperkinetic movements were the most common reason for cvEEG in patients with ES (84%). None of the patients undergoing cvEEG for persistent coma (29% of all patients) had ES. Focal slowing (67 vs. 10%), sporadic interictal epileptiform discharges (EDs; 33 vs. 6%), and periodic/rhythmic EDs (67 vs. 1%) were proportionally more frequent among patients with electrographic seizures than those without these seizures. While 15% of patients without ES had generalized periodic discharges (GPDs) with triphasic morphology on EEG, none of the patients with ES had this pattern. Further study is required to assess the predictive values of these risk factors on electrographic seizure incidence and subsequent outcomes.

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily causes respiratory illness. However, neurological sequelae from novel coronavirus disease 2019 (COVID-19) can occur. Patients with neurological conditions may be at higher risk of developing worsening of their underlying problem. Here we document our initial experiences as neurologic consultants at a single center quaternary hospital at the epicenter of the COVID-19 pandemic.Methods: This was a retrospective case series of adult patients diagnosed with SARS-CoV-2 who required neurological evaluation in the form of a consultation or primary neurological care from March 13, 2020 to April 1, 2020.Results: Thirty-three patients (ages 17–88 years) with COVID-19 infection who required neurological or admission to a primary neurology team were included in this study. The encountered neurological problems associated with SARS-CoV-2 infection were encephalopathy (12 patients, 36.4%), seizure (9 patients, 27.2%), stroke (5 patients, 15.2%), recrudescence of prior neurological disease symptoms (4 patients, 12.1%), and neuromuscular (3 patients, 9.1%). The majority of patients who required evaluation by neurology had elevated inflammatory markers. Twenty-one (63.6%) patients were discharged from the hospital and 12 (36.4%) died from COVID-19 related complications.Conclusion: This small case series of our initial encounters with COVID-19 infection describes a range of neurological complications which are similar to presentations seen with other critical illnesses. COVID-19 infection did not change the overall management of neurological problems.

Abstract Background Cerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM. Methods Patients included in the study were admitted (2009–2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization. Results In this cohort of 94 patients, median age was 44 (interquartile range 29–62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44–56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45–9.35). Conclusions Elevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.

Abstract Background Over 900 travel-associated Zika virus cases have been identified in New York City (NYC), New York. A survey was administered in NYC adapted from the Knowledge, Attitudes, and Practices (KAP) survey on Zika virus developed by the World Health Organization (WHO). Methods A standardized, self-administered, anonymous questionnaire was administered to a convenience sample in Manhattan and the Bronx from June 30th, 2016 to October 21st, 2016. Responses were grouped into six domains based on the content and structure of the questions and were summarized using descriptive statistics or converted into a continuous knowledge score and assessed for associations with pregnancy status and travel history using linear regression. Results There were 224 respondents with a mean age of 33 (SD ± 11.6) with 77% (170/224) female and 24% (51/224) pregnant. The majority (98% (213/217)) were unable to identify all of the symptoms associated with acute Zika virus infection and all modes of transmission (97% (213/219)). Most participants (85% (187/219)) identified mosquitoes as a mode of transmission. 95% (116/122) reported an association between Zika virus and microcephaly. The most concerning aspect of Zika virus in 46% (91/200) was the risk of disabilities to babies, and risk of sexual transmission (25% (49/200)). When asked what precautions pregnant persons should to reduce the risk of transmission when traveling to a Zika endemic region, only 27% (50/185) identified using condoms during intercourse or refraining from intercourse while pregnant. Knowledge of Zika transmission is significantly positively associated with pregnancy status, but not with travel history. Conclusion Our results indicate an overall poor understanding of Zika virus symptoms and possible complications, transmission modes, and current recommended prevention guidelines. Pregnancy is positively associated with Knowledge of Zika Transmission, but not other knowledge scores. Reported travel history to Zika endemic regions is not significantly associated with Zika knowledge. There is a need for implementing future public health interventions that particularly focus on protection against Zika transmission, that Zika is sexually transmitted, and risks that the Guillain-Barré Syndrome poses a risk to adults.

The emergence of immune-based treatments for cancer has led to a growing field dedicated to understanding and managing iatrogenic immunotoxicities that arise from these agents. Immune-related adverse events (irAEs) can develop as isolated events or as toxicities affecting multiple body systems. In particular, this review details the neurological irAEs from immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell immunotherapies. The recognition and treatment of neurological irAEs has variable success, depending on the severity and nature of the neurological involvement. Understanding the involved mechanisms, predicting those at higher risk for irAEs, and establishing safety parameters for resuming cancer immunotherapies after irAEs are all important fields of ongoing research.

ABSTRACT Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively). IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.

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.