Clinical Significance of Positive Results of the BioFire Cerebrospinal Fluid FilmArray Meningitis/Encephalitis Panel at a Tertiary Medical Center in the United States.

CONTEXT.­: The FilmArray Meningitis/Encephalitis (ME) panel is the first US Food and Drug Administration-cleared multiplex polymerase chain reaction panel for the detection of central nervous system infections. While the assay's performance characteristics have been described, the real-world significance of positive results has not been fully characterized. OBJECTIVE.­: To evaluate the clinical significance of positive ME panel results in a tertiary care medical center in New York, New York. DESIGN.­: Four physicians independently performed retrospective clinical assessments of all positive ME panel results at Columbia University Irving Medical Center, including the Children's Hospital of New York, during an 18-month period. Each reviewer determined the likelihood of central nervous system infection for all cases and whether cases fit Brighton diagnostic criteria for meningitis, encephalitis, or meningoencephalitis. RESULTS.­: Among 119 cases, there was 75% positive agreement (95% CI, 54%-89%) between ME panel results and clinical consensus, which varied among panel targets. CONCLUSIONS.­: The ME panel showed good agreement with expert clinical consensus for patients presenting with acute meningitis/encephalitis. Factors contributing to clinically insignificant ME positive results included low pretest probability, traumatic lumbar puncture, specimen contamination, and detection of incidental viral targets such as human herpesvirus 6. Notably, the ME panel detected more than twice the number of cases of bacterial meningitis detected by culture alone, particularly among patients receiving empiric antimicrobial therapy before lumbar puncture. Appropriate test use and contextual interpretation of results are critical to leveraging the advantages of the platform while avoiding potential pitfalls.

Aetiology and outcome of non-traumatic coma in African children: protocol for a systematic review and meta-analysis.

BACKGROUND: Non-traumatic coma is a common acute childhood presentation to healthcare facilities in Africa and is associated with high morbidity and mortality. Historically, the majority of cases were attributed to cerebral malaria (CM). With the recent drastic reduction in malaria incidence, non-malarial coma is becoming a larger proportion of cases and determining the aetiology is diagnostically challenging, particularly in resource-limited settings. The purpose of this study will be to evaluate the aetiology and prognosis of non-traumatic coma in African children. METHODS: With no date restrictions, systematic searches of MEDLINE, Embase, and Scopus will identify prospective and retrospective studies (including randomised controlled trials, cluster randomised trials, cohort studies, cross-sectional, and case-control studies) recruiting children (1 month-16 years) with non-traumatic coma (defined by Blantyre Coma Score ≤ 2 or comparable alternative) from any African country. Disease-specific studies will be included if coma is associated and reported. The primary outcome is to determine the aetiology (infectious and non-infectious) of non-traumatic coma in African children, with pooled prevalence estimates of causes (e.g., malaria). Secondary outcomes are to determine overall estimates of morbidity and mortality of all-cause non-traumatic coma and disease-specific states of non-traumatic coma, where available. Random effects meta-analysis will summarise aetiology data and in-hospital and post-discharge mortality. Heterogeneity will be quantified with τ2, I2, and Cochran's Q test. DISCUSSION: This systematic review will provide a summary of the best available evidence on the aetiology and outcome of non-traumatic coma in African children. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020141937.

COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital.

Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.

"We can't handle things we don't know about": perceived neurorehabilitation challenges for Malawian paediatric cerebral malaria survivors.

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.

Central nervous system (CNS) enterovirus infections: A single center retrospective study on clinical features, diagnostic studies, and outcome.

Enteroviruses (EV) are responsible for a large number of meningoencephalitis cases, especially in children. The objective of this study was to identify modes of diagnosis including the significance of respiratory and cerebrospinal fluid samples, associated clinical characteristics, inpatient management, and outcome of individuals with EV infections of the central nervous system (CNS). Electronic medical records of individuals with enterovirus infections of the CNS who presented to the Columbia University Irving Medical Center and Children's Hospital of New York between January 1, 2012 and December 31, 2017 were reviewed retrospectively for demographic, epidemiological, and clinical data. The median age overall was 1.7 months (interquartile range 14 years) and most (62.4%) were male. The majority of CNS infections presented as meningitis (95.7%) and occurred in the summer (45.2%) and fall seasons (37.6%). Eighty-five cases (91.4%) demonstrated EV positivity in cerebrospinal fluid, thirty cases (32.3%) exhibited both cerebrospinal fluid and respiratory positivity, and eight cases (8.6%) exhibited respiratory positivity with coinciding neurological findings. Eighty-nine individuals overall (95.7%) received antibiotics and 37 (39.8%) received antiviral treatment. All surviving individuals had favorable Modified Rankin Scores (MRS) within the zero to two ranges upon discharge. Testing respiratory samples in addition to cerebrospinal fluid was found to be an important diagnostic tool in EV-associated cases. While clinical outcomes were favorable for an overwhelming majority of cases, etiological understanding of CNS infections is essential for identifying ongoing and changing epidemiological patterns and aid in improving the diagnosis and treatment.

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.

Global HIV neurology: a comprehensive review.

: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on long-standing combination antiretroviral therapy (cART). Importantly, growing evidence shows that the central nervous system (CNS) may serve as a reservoir for viral replication, which has major implications for HIV eradication strategies. Although there has been major progress in the last decade in our understanding of the pathogenesis, burden, and impact of neurological conditions associated with HIV infection, significant scientific gaps remain. In many resource-limited settings, antiretrovirals considered second or third line in the United States, which carry substantial neurotoxicity, remain mainstays of treatment, and patients continue to present with severe immunosuppression and CNS opportunistic infections. Despite this, increased global access to cART has coincided with an aging HIV-positive population with cognitive sequelae, cerebrovascular disease, and peripheral neuropathy. Further neurological research in low-income and middle-income countries (LMICs) is needed to address the burden of neurological complications in HIV-positive patients, particularly regarding CNS viral reservoirs and their effects on eradication.

A pilot educational intervention for headache and concussion: The headache and arts program.

OBJECTIVE: Using a science, technology, engineering, arts, and mathematics (STEAM) curriculum, we developed, piloted, and tested the Headache and Arts Program. This program seeks to increase knowledge and awareness of migraine and concussion among high school students through a visual arts-based curriculum. METHODS: We developed a 2-week Headache and Arts Program with lesson plans and art assignments for high school visual arts classes and an age-appropriate assessment to assess students' knowledge of migraine and concussion. We assessed students' knowledge through (1) the creation of artwork that depicted the experience of a migraine or concussion, (2) the conception and implementation of methods to transfer knowledge gained through the program, and (3) preassessment and postassessment results. The assessment was distributed to all students prior to the Headache and Arts Program. In a smaller sample, we distributed the assessment 3 months after the program to assess longitudinal effects. Descriptive analyses and p values were calculated using SPSS V.24 and Microsoft Excel. RESULTS: Forty-eight students participated in the research program. Students created artwork that integrated STEAM knowledge learned through the program and applied creative methods to teach others about migraine and concussion. At baseline, students' total scores averaged 67.6% correct. Total scores for the longitudinal preassessment, immediate postassessment, and delayed 3-month postassessment averaged 69.4%, 72.8%, and 80.0% correct, respectively. CONCLUSION: The use of a visual arts-based curriculum may be effective for migraine and concussion education among high school students.

Meta-Synthesis on Migraine Management.

BACKGROUND: Migraine is one of the top 10 most disabling conditions among adults worldwide. Most migraine research is quantitative and indicates concerns about medication adherence, stigma, and more. Qualitative studies might reveal an improved understanding of migraine patients' perspectives regarding migraine treatment. OBJECTIVE: The aim of this study was to synthesize the qualitative research on migraine patients' perspectives regarding migraine treatment to (a) identify common patterns across various types of migraine treatment studies and (b) inform future research. METHODS: A systematic search for qualitative studies in the HA (HA) literature was conducted in Medline (PubMed), PsycINFO, EMBASE, CINAHL, Web of Science, Joanna Briggs Institute EBP Database, and The Cochrane Library. Search terms (subject headings and keywords) were HA, HA disorders, migraine, qualitative studies, and qualitative research. Qualitative studies were systematically identified by using published qualitative search filters recommended by The InterTASC Information Specialists' Sub-Group (ISSG). The search was limited to English only, peer reviewed publications, and studies published between 1996 and 2016. For screening, additional inclusion criteria were (1) adult migraine patients; (2) must mention treatment in the title or study design of the abstract. Ten studies met the inclusion criteria. The Critical Appraisal Skills Program tool was applied to appraise study quality. Thematic analysis produced the codes and themes. Two authors read articles separately and individually created codes. Code lists were synthesized and themes emerged iteratively from the process. RESULTS: Study sample sizes ranged from 10 to 33 participants, with our findings representing 161 participants. Data were collected either using interviews or focus groups. The more common methodologies were grounded theory and phenomenology. Few (3) studies described the number of headache (HA) days for inclusion in the study. Eight out of 10 used International Classification of Headache Disorders (ICHD) criteria. Our synthesis produced five major themes. The first theme was "Migraine patients' difficulties with health care utilization," and it included issues surrounding the cost of migraine treatment (seeing providers and prescription medications). The second theme was "Migraine patients' perceived relationships with their providers," which included the role and relationship with the provider, as well as trust in the provider and the providers' knowledge in managing HAs. The third theme was "Thoughts about the various migraine treatments." It was based on patients' comments indicating an aversion to prescription medications, the use of non-pharmacological interventions for treatment, behavioral modification as a form of treatment, and the need for additional treatment options. The fourth and fifth themes were "Understanding diagnosis/triggers" and "Societal implications," respectively. The latter theme included feelings of not being taken seriously and issues surrounding quality of life. DISCUSSION: The metasynthesis revealed several key commonalities regarding patients' perspectives on migraine treatment and identified new areas for research using a qualitative approach. Researchers conducting qualitative research with patients experiencing migraines might consider using and reporting more of the inclusion and exclusion criteria commonly used in migraine research, for example, reporting whether the ICHD criteria were used and the number of HA days for patients to be in a study. Future studies might be done to determine how the role of allied health care providers, for example, pharmacists, physical therapists, and psychologists, might be expanded to help with migraine treatment and ultimately to improve patient outcomes.

A Retrospective Nested Cohort Study of Emergency Department Revisits for Migraine in New York City.

OBJECTIVE: Migraine causes more than 1.2 million visits to US emergency departments (EDs) annually. Many of these visits are revisits among patients who had already been treated in an ED for migraine. The goal of this analysis was to determine the frequency of headache revisits among patients who present to an ED for management of migraine and sociodemographic factors associated with the revisit. METHODS: Using the New York City Department of Health and Mental Hygiene Syndromic Surveillance database, we conducted a retrospective nested cohort study. We analyzed visits from 18 NYC EDs with discharge diagnoses in the first 6 months of 2015. We conducted descriptive analyses to determine the frequency of headache revisit within 6 months of an index ED visit for migraine and the elapsed time to revisit. Using multivariable logistic regression, we assessed associations between age, sex, poverty, and revisit. RESULTS: Of 1052 ED visits with an ED discharge diagnosis of migraine during the first 6 months of 2015, 277 (26.3%) had a headache revisit within 6 months of their initial migraine visit and 131 (12.5%) had two or more revisits at the same hospital. Of the revisits for headache, 9% occur within 72 hours and 46% occur within 90 days of the initial migraine visit. Sex, age, and poverty level were not associated with an ED revisit. CONCLUSION: More than a quarter of initial ED visits for migraine are followed by headache revisits in <6 months. Future work should target interventions to decrease the frequency of headache revisits.

Post-Concussive Syndrome: a Focus on Post-Traumatic Headache and Related Cognitive, Psychiatric, and Sleep Issues.

PURPOSE OF REVIEW: Post-traumatic headache (PTH) is a secondary headache disorder following traumatic brain injury. We sought to examine the recent literature on PTH and associated cognitive, psychiatric, and sleep conditions to understand the latest findings about the associated conditions and available screening tools, and to understand the available treatment options for PTH. RECENT FINDINGS: Up to one third of PTH patients may have depression and about one quarter may have insomnia. Anxiety and cognitive issues are also common. While there are few studies examining abortive medications for PTH, recent studies of preventive medications examine the efficacy of topiramate, and topiramate may be better than other oral preventive medications. Other currently investigated treatments include nerve blocks, onabotulinum toxin A, transmagnetic stimulation, and behavioral therapy (biofeedback). Due to an expanded focus on and knowledge of concussion and PTH, comorbid psychiatric, cognitive, and sleep issues have become more widely acknowledged and studied. However, more high-quality studies must be conducted to examine the underlying pathophysiology of PTH and associated symptoms and to determine the most effective abortive and preventive treatment options.

Probable Immunoglobulin Subtype-G4-Related Disease in the Head and Neck from Foreign Body Injection: A Case Report.

Introduction Immunoglobulin subtype G4-related disease (IgG4-RD) is a fibroinflammatory disease of unknown etiology, with manifestations involving nearly every organ system. Its association with foreign bodies is not established. Here, we present a novel case of IgG4-RD in response to foreign body injection. Case Description A 58-year-old woman presented with history of persistent left facial pain, xerophthalmia, blurred vision, and trismus. The patient's medical history was significant for left-sided temporomandibular joint (TMJ) reconstruction with silicone injection into the joint. Magnetic resonance imaging revealed a lesion in the left skull base. Biopsies demonstrated the cardinal histopathological features of IgG4-RD. The patient was treated with a tapering dose of prednisolone followed by rituximab, resulting in tumor shrinkage and resolution of her symptoms. Discussion This is the first reported case of IgG4-RD potentially precipitated by a foreign body, in this case injected silicone into the TMJ. The pathogenesis and etiology of IgG4-RD is still not fully elucidated, but allergic and reactive inflammatory reactions have been implicated in the disease process. This case report should raise the idea of reactive foreign bodies as a causative agent for IgG4-RD.