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The University of California San Francisco Neurology Department incorporated a formal diversity, equity, and inclusion curriculum into the residency education in 2015. During that time, we have learned a number of lessons that can be useful to other institutions planning similar initiatives including the following: (1) training should be led by a multidisciplinary team with experienced educators, (2) sustainability of the curriculum requires broad departmental buy-in from leadership to junior faculty to the residents themselves, (3) the curriculum needs to balance training on fundamental topics with flexibility to change in response to current events and the needs of the community, and (4) the sessions need to be practical.

BackgroundLower-grade insular gliomas often appear as expansile and infiltrative masses on magnetic resonance imaging (MRI). However, there are nonneoplastic lesions of the insula, such as demyelinating disease and vasculopathies, that can mimic insular gliomas.ObservationsThe authors report two patients who presented with headaches and were found to have mass lesions concerning for lower-grade insular glioma based on MRI obtained at initial presentation. However, on the immediate preoperative MRI obtained a few weeks later, both patients had spontaneous and complete resolution of the insular lesions.LessonsTumor mimics should always be in the differential diagnosis of brain masses, including those involving the insula. The immediate preoperative MRI (within 24-48 hours of surgery) must be compared carefully with the initial presentation MRI to assess interval change that suggests tumor mimics to avoid unnecessary surgical intervention.

ImportanceCerebrospinal fluid (CSF) cytologic testing and flow cytometry are insensitive for diagnosing neoplasms of the central nervous system (CNS). Such clinical phenotypes can mimic infectious and autoimmune causes of meningoencephalitis.ObjectiveTo ascertain whether CSF metagenomic next-generation sequencing (mNGS) can identify aneuploidy, a hallmark of malignant neoplasms, in difficult-to-diagnose cases of CNS malignant neoplasm.Design, setting, and participantsTwo case-control studies were performed at the University of California, San Francisco (UCSF). The first study used CSF specimens collected at the UCSF Clinical Laboratories between July 1, 2017, and December 31, 2019, and evaluated test performance in specimens from patients with a CNS malignant neoplasm (positive controls) or without (negative controls). The results were compared with those from CSF cytologic testing and/or flow cytometry. The second study evaluated patients who were enrolled in an ongoing prospective study between April 1, 2014, and July 31, 2019, with presentations that were suggestive of neuroinflammatory disease but who were ultimately diagnosed with a CNS malignant neoplasm. Cases of individuals whose tumors could have been detected earlier without additional invasive testing are discussed.Main outcomes and measuresThe primary outcome measures were the sensitivity and specificity of aneuploidy detection by CSF mNGS. Secondary subset analyses included a comparison of CSF and tumor tissue chromosomal abnormalities and the identification of neuroimaging characteristics that were associated with test performance.ResultsAcross both studies, 130 participants were included (median [interquartile range] age, 57.5 [43.3-68.0] years; 72 men [55.4%]). The test performance study used 125 residual laboratory CSF specimens from 47 patients with a CNS malignant neoplasm and 56 patients with other neurological diseases. The neuroinflammatory disease study enrolled 12 patients and 17 matched control participants. The sensitivity of the CSF mNGS assay was 75% (95% CI, 63%-85%), and the specificity was 100% (95% CI, 96%-100%). Aneuploidy was detected in 64% (95% CI, 41%-83%) of the patients in the test performance study with nondiagnostic cytologic testing and/or flow cytometry, and in 55% (95% CI, 23%-83%) of patients in the neuroinflammatory disease study who were ultimately diagnosed with a CNS malignant neoplasm. Of the patients in whom aneuploidy was detected, 38 (90.5%) had multiple copy number variations with tumor fractions ranging from 31% to 49%.Conclusions and relevanceThis case-control study showed that CSF mNGS, which has low specimen volume requirements, does not require the preservation of cell integrity, and was orginally developed to diagnose neurologic infections, can also detect genetic evidence of a CNS malignant neoplasm in patients in whom CSF cytologic testing and/or flow cytometry yielded negative results with a low risk of false-positive results.

BackgroundDelirium is associated with poor clinical outcomes that could be improved with targeted interventions.ObjectiveTo determine whether a multicomponent delirium care pathway implemented across seven specialty nonintensive care units is associated with reduced hospital length of stay (LOS). Secondary objectives were reductions in total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use.MethodsThis retrospective cohort study included 22,708 hospitalized patients (11,018 preintervention) aged ≥50 years encompassing seven nonintensive care units: neurosciences, medicine, cardiology, general and specialty surgery, hematology-oncology, and transplant. The multicomponent delirium care pathway included a nurse-administered delirium risk assessment at admission, nurse-administered delirium screening scale every shift, and a multicomponent delirium intervention. The primary study outcome was LOS for all units combined and the medicine unit separately. Secondary outcomes included total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use.ResultsAdjusted mean LOS for all units combined decreased by 2% post intervention (proportional change, 0.98; 95% CI, 0.96-0.99; P = .0087). Medicine unit adjusted LOS decreased by 9% (proportional change, 0.91; 95% CI, 0.83-0.99; P = .028). For all units combined, adjusted odds of 30-day readmission decreased by 14% (odds ratio [OR], 0.86; 95% CI, 0.80-0.93; P = .0002). Medicine unit adjusted cost decreased by 7% (proportional change, 0.93; 95% CI, 0.89-0.96; P = .0002).ConclusionThis multicomponent hospital-wide delirium care pathway intervention is associated with reduced hospital LOS, especially for patients on the medicine unit. Odds of 30-day readmission decreased throughout the entire cohort.

BackgroundCurrently, most basilar artery aneurysms (BAAs) are treated endovascularly. Surgery remains an appropriate therapy for a subset of all intracranial aneurysms. Whether open microsurgery would be required or utilized, and to what extent, for BAAs treated by a surgeon who performs both endovascular and open procedures has not been reported.MethodsRetrospective analysis of prospectively maintained, single-surgeon series of BAAs treated with endovascular or open surgery from the first 5 years of practice.ResultsForty-two procedures were performed in 34 patients to treat BAAs-including aneurysms arising from basilar artery apex, trunk, and perforators. Unruptured BAAs accounted for 35/42 cases (83.3%), and the mean aneurysm diameter was 8.4 ± 5.4 mm. Endovascular coiling-including stent-assisted coiling-accounted for 26/42 (61.9%) treatments and led to complete obliteration in 76.9% of cases. Four patients in the endovascular cohort required re-treatment. Surgical clip reconstruction accounted for 16/42 (38.1%) treatments and led to complete obliteration in 88.5% of cases. Good neurologic outcome (mRS ≤ 2) was achieved in 88.5% and 75.0% of patients in endovascular and open surgical cohorts, respectively (p = 0.40). Univariate logistic regression analysis demonstrated that advanced age (OR 1.11[95% CI 1.01-1.23]) or peri-procedural adverse event (OR 85.0 [95% CI 6.5-118.9]), but not treatment modality (OR 0.39[95% CI 0.08-2.04]), was the predictor of poor neurologic outcome.ConclusionsComplementary implementation of both endovascular and open surgery facilitates individualized treatment planning of BAAs. By leveraging strengths of both techniques, equivalent clinical outcomes and technical proficiency may be achieved with both modalities.

ObjectivesCocaine use has been linked to stroke in several studies. However, few studies have considered the influence of cocaine use on stroke mechanisms such as small vessel disease (SVD). We conducted a study to assess associations between the toxicology-confirmed use of multiple drugs, including cocaine, and a marker of SVD, white matter hyperintensities (WMH).Materials and methodsWe conducted a nested case-control study (n = 30) within a larger cohort study (N = 245) of homeless and unstably housed women recruited from San Francisco community venues. Participants completed six monthly study visits consisting of an interview, blood draw, vital sign assessment and baseline brain MRI. We examined associations between toxicology-confirmed use of multiple substances, including cocaine, methamphetamine, heroin, alcohol and tobacco, and WMH identified on MRI.ResultsMean study participant age was 53 years, 70% of participants were ethnic minority women and 86% had a history of cocaine use. Brain MRIs indicated the presence of WMH (i.e., Fazekas score>0) in 54% (18/30) of imaged participants. The odds of WMH were significantly higher in women who were toxicology-positive for cocaine (Odd Ratio=7.58, p=0.01), but not in women who were toxicology-positive for other drugs or had several other cerebrovascular risk factors.ConclusionsOver half of homeless and unstably housed women showed evidence of WMH. Cocaine use is highly prevalent and a significant correlate of WMH in this population, while several traditional CVD risk factors are not. Including cocaine use in cerebrovascular risk calculators may improve stroke risk prediction in high-risk populations and warrants further investigation.

ObjectiveTo examine the use of benzodiazepines and the association between low benzodiazepine dose, breakthrough seizures, and respiratory support in patients with status epilepticus.MethodsIn this cross-sectional analysis of adult patients with status epilepticus treated by an emergency medical services agency from 2013 to 2018, the primary outcome was treatment with a second benzodiazepine dose, an indicator for breakthrough seizure. The secondary outcome was receiving respiratory support. Midazolam was the only benzodiazepine administered.ResultsAmong 2,494 patients with status epilepticus, mean age was 54.0 years and 1,146 (46%) were female. There were 1,537 patients given midazolam at any dose, yielding an administration rate of 62%. No patients received a dose and route consistent with national guidelines. Rescue therapy with a second midazolam dose was required in 282 (18%) patients. Higher midazolam doses were associated with lower odds of rescue therapy (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-0.9) and were not associated with increased respiratory support. If anything, higher doses of midazolam were associated with decreased need for respiratory support after adjustment (OR, 0.9; 95% CI, 0.8-1.0).ConclusionsAn overwhelming majority of patients with status epilepticus did not receive evidence-based benzodiazepine treatment. Higher midazolam doses were associated with reduced use of rescue therapy and there was no evidence of respiratory harm, suggesting that benzodiazepines are withheld without clinical benefit.Classification of evidenceThis study provides Class III evidence that for patients with status epilepticus, higher doses of midazolam led to a reduced use of rescue therapy without an increased need for ventilatory support.

ObjectiveDuring the COVID-19 pandemic, quaternary-care facilities continue to provide care for patients in need of urgent and emergent invasive procedures. Perioperative protocols are needed to streamline care for these patients notwithstanding capacity and resource constraints.MethodsA multidisciplinary panel was assembled at the University of California, San Francisco, with 26 leaders across 10 academic departments, including 7 department chairpersons, the chief medical officer, the chief operating officer, infection control officers, nursing leaders, and resident house staff champions. An epidemiologist, an ethicist, and a statistician were also consulted. A modified two-round, blinded Delphi method based on 18 agree/disagree statements was used to build consensus. Significant disagreement for each statement was tested using a one-sided exact binomial test against an expected outcome of 95% consensus using a significance threshold of p < 0.05. Final triage protocols were developed with unblinded group-level discussion.ResultsOverall, 15 of 18 statements achieved consensus in the first round of the Delphi method; the 3 statements with significant disagreement (p < 0.01) were modified and iteratively resubmitted to the expert panel to achieve consensus. Consensus-based protocols were developed using unblinded multidisciplinary panel discussions. The final algorithms 1) quantified outbreak level, 2) triaged patients based on acuity, 3) provided a checklist for urgent/emergent invasive procedures, and 4) created a novel scoring system for the allocation of personal protective equipment. In particular, the authors modified the American College of Surgeons three-tiered triage system to incorporate more urgent cases, as are often encountered in neurosurgery and spine surgery.ConclusionsUrgent and emergent invasive procedures need to be performed during the COVID-19 pandemic. The consensus-based protocols in this study may assist healthcare providers to optimize perioperative care during the pandemic.

Collaboration within a complicated organization is inherently challenging and can be fraught with discord. Recent emphasis on interdisciplinary and collaborative teamwork in neurology has brought this issue to the forefront of daily practice. The health care system can be complex and opaque, and the stakes-human life-are high. Medical team conflict has been associated with decreased subjective effectiveness, less job satisfaction, and increase in errors. As specialists, neurologists are necessarily embedded within a network of providers and must be adept in the understanding and management of conflictual situations. For the practicing neurologist, it is important to understand team conflict dynamics. Here, management strategies are provided that illustrate how individual neurologists can serve as effective leaders who mitigate harmful effects and capitalize on benefits of team conflict on performance.

Ischemic stroke is one of the most debilitating and deadliest conditions worldwide. Intravenous t-PA is the current standard treatment within 4 hours after onset of symptoms. Recent randomized controlled trials have demonstrated the efficacy of neurointerventional intra-arterial treatment in acute ischemic stroke. About 20% of acute ischemic stroke are classified as wake-up strokes, which falls out of the conventional treatment time window. New evidence suggests that some patients with longer time from symptom onset (up to 24 hours) may benefit from thrombectomy, probably in part due to variations in collateral circulation among individual patients. Advanced imaging can play a crucial role in identifying patients who could benefit from endovascular intervention presenting within extended treatment time windows. In this article, we review the advanced imaging algorithm for ischemic stroke workup in the multiple studies published to date and summarize the results of the clinical trials for late ischemic stroke that can be clinically useful.

ImportanceCurrent attempts to gauge the acute care needs of patients with dementia have not effectively addressed the role of caregivers, despite their extensive involvement in decisions about acute care management.ObjectiveTo determine whether caregiver depression is associated with increased use of the emergency department (ED) among patients with dementia.Design, setting, and participantsThis longitudinal cohort study used data from the Care Ecosystem study, a randomized clinical trial examining telephone-based supportive care for patients with dementia and their caregivers. Patients were 45 years or older with any type of dementia. A total of 780 caregiver-patient dyads were enrolled from March 20, 2015, until February 28, 2017, and 663 dyads contributed baseline and 6-month data and were included in the analysis.ExposuresCaregiver depression (9-item Patient Health Questionnaire score of ≥10). Secondary analyses examined caregiver burden and self-efficacy.Main outcomes and measuresThe primary outcome was the number of ED visits in a 6-month period.ResultsAmong the 663 caregivers (467 women and 196 men; mean [SD] age, 64.9 [11.8] years), 84 caregivers (12.7%) had depression at baseline. The mean incidence rate of ED visits was 0.9 per person-year. Rates of ED presentation were higher among dyads whose caregiver did vs did not have depression (1.5 vs 0.8 ED visits per person-year). In a Poisson regression model adjusting for patient age, sex, severity of dementia, number of comorbidities, and baseline ED use, as well as caregiver age and sex, caregiver depression continued to be associated with ED use, with a 73% increase in rates of ED use among dyads with caregivers with depression (adjusted incident rate ratio, 1.73; 95% CI, 1.30-2.30). Caregiver burden was associated with higher ED use in the unadjusted model, but this association did not reach statistical significance after adjustment (incident rate ratio, 1.19; 95% CI, 0.93-1.52). Caregiver self-efficacy was inversely proportional to the number of ED visits in the unadjusted and adjusted models (adjusted incident rate ratio, 0.96; 95% CI, 0.92-0.99).Conclusions and relevanceAmong patients with dementia, caregiver depression appears to be significantly associated with increased ED use, revealing a key caregiver vulnerability, which, if addressed with patient- and caregiver-centered dementia care, could improve health outcomes and lower costs for this high-risk population.

OBJECTIVE:To identify molecular correlates of primary angiitis of the CNS (PACNS) through proteomic analysis of CSF from a biopsy-proven patient cohort. METHODS:Using mass spectrometry, we quantitatively compared the CSF proteome of patients with biopsy-proven PACNS (n = 8) to CSF from individuals with noninflammatory conditions (n = 11). Significantly enriched molecular pathways were identified with a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.5 and concordant Benjamini-Hochberg-adjusted p < 0.05 on DeSeq and t test) were identified as differentially regulated proteins. RESULTS:Compared to noninflammatory controls, 283 proteins were differentially expressed in the CSF of patients with PACNS, with significant enrichment of the complement cascade pathway (C4-binding protein, CD55, CD59, properdin, complement C5, complement C8, and complement C9) and neural cell adhesion molecules. A subset of clinically relevant findings were validated by Western blot and commercial ELISA. CONCLUSIONS:In this exploratory study, we found evidence of deregulation of the alternative complement cascade in CSF from biopsy-proven PACNS compared to noninflammatory controls. More specifically, several regulators of the C3 and C5 convertases and components of the terminal cascade were significantly altered. These preliminary findings shed light on a previously unappreciated similarity between PACNS and systemic vasculitides, especially anti-neutrophil cytoplasmic antibody-associated vasculitis. The therapeutic implications of this common biology and the diagnostic and therapeutic utility of individual proteomic findings warrant validation in larger cohorts.

BackgroundTo explore intubation rates among patients with status epilepticus (SE) and the degree of institutional variation.MethodsSerial cross-sectional study of SE-related hospitalizations from 2004 to 2013 using data from the National Inpatient Sample. The primary outcome was intubation of patients with SE. Multivariable models identified predictors of intubation, institutional variation in intubation rates, and the proportion of variance attributable to individual hospitals. This analysis was repeated using data from 5 states in the State Inpatient Databases (SID).ResultsThere were 119 337 SE hospitalizations. The overall intubation rate was 32.7% (95% confidence interval [CI]: 32.2%-33.3%). There was marked variation in estimated intubation rates, ranging from 2% to 80% in the lowest and highest quintile after adjustment. There was somewhat less variability in the SID cohort where quintiles ranged from 10% to 54%. Those undergoing intubation were more often men and presenting with stroke, intracerebral hemorrhage, central nervous system infection, hyponatremia, and alcohol withdrawal. Urban location (odds ratio [OR]: 3.8, 95% CI: 2.7-5.5) and hospitalization at a teaching institution (OR: 3.9, 95% CI: 1.2-12.6) were even stronger predictors of intubation after adjustment for clinical factors. A regression including both patient- and hospital-level variables to predict intubation also performed better than a regression including patient factors alone (C statistic 0.81 vs 0.59, respectively).ConclusionsThere is considerable institutional variation in intubation rates for SE independent of patient characteristics suggesting that decisions around intubation rest heavily on where one is hospitalized. Further work is needed to clarify how this variation influences outcomes.

BackgroundMetagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.MethodsIn a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.ResultsWe enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.ConclusionsRoutine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).

ObjectiveTo characterize the most common neurologic diagnoses leading to hospitalization for homeless compared to housed individuals and to assess whether homelessness is an independent risk factor for 30-day readmission after an admission for a neurologic illness.MethodsWe performed a retrospective serial cross-sectional study using data from the Healthcare Cost and Utilization Project California State Inpatient Database from 2006 to 2011. Adult patients with a primary neurologic discharge diagnosis were included. The primary outcome was 30-day readmission. We used multilevel logistic regression to examine the association between homelessness and readmission after adjustment for patient factors.ResultsWe identified 1,082,347 patients with a neurologic primary diagnosis. The rate of homelessness was 0.37%. The most common indications for hospitalization among homeless patients were seizure and traumatic brain injury, both of which were more common in the homeless compared to housed population (19.3% vs 8.1% and 31.9% vs 9.2%, respectively, p < 0.001). A multilevel mixed-effects model controlling for patient age, sex, race, insurance type, comorbid conditions, and clustering on the hospital level found that homelessness was associated with increased 30-day readmission (odds ratio 1.5, 95% confidence interval 1.4-1.6, p < 0.001). This association persisted after this analysis was repeated within specific diagnoses (patients with epilepsy, trauma, encephalopathy, and neuromuscular disease).ConclusionThe most common neurologic reasons for admission among homeless patients are seizure and traumatic brain injury; these patients are at high risk for readmission. Future interventions should target the drivers of readmissions in this vulnerable population.

Background and purposeNeurohospitalist neurology is a fast-growing subspecialty with a variety of practice settings featuring neurohospitalist models of care. Since inception, the subspecialty has responded to new challenges in resident training, hospital reimbursement, practice, and burnout.MethodsTo characterize neurohospitalists' current practice and perspectives, we surveyed the neurohospitalists and trainees affiliated with the Neurohospitalist Society using an electronic survey distributed through the society listserv.ResultsOf 501 individuals surveyed by e-mail, 119 began the survey (23.8% response rate), with 88.2% self-identifying as neurohospitalists. Most neurohospitalists (63%) are 10 years or less out of training, devoting 70% of their professional time to inpatient clinical activities while also performing administrative or teaching activities. Only 38% are employed by an academic department. Call schedules are common, with 75% of neurohospitalists participating in a hospital or emergency call schedule, while 55% provide telemedicine services. The majority (97%) of neurohospitalists primarily care for adults, most commonly treating patients with cerebrovascular disease, seizures, and delirium/encephalopathy. The majority (87%) are overall pleased with their work, but 36% report having experienced burnout.ConclusionsNeurohospitalists are a diverse group of neurologists primarily practicing in the inpatient setting while performing a variety of additional activities. They provide a wide array of clinical expertise for acute neurological diseases and neurological emergencies that require hospitalization, including stroke, seizure, and encephalopathy. Neurohospitalists in general are very pleased with their work, while burnout, as in neurology and other areas of medicine, remains a concern.

BackgroundStudies of emergent neuroimaging in the management of patients presenting with a breakthrough seizure are lacking. We sought to determine how often emergent computed tomography (CT) scans are obtained in patients with known epilepsy presenting with a seizure and how often acute abnormalities are found.MethodsThis multicenter retrospective cohort study was performed in the emergency department at 2 academic medical centers. The primary outcomes were percentage of visits where a CT scan was obtained, whether CT findings represented acute abnormalities, and whether these findings changed acute management.ResultsOf the 396 visits included, CT scans were obtained in 39%, and 8% of these scans demonstrated acute abnormalities. Patients who were older, had status epilepticus, a brain tumor, head trauma, or an abnormal examination were all significantly more likely to undergo acute neuroimaging (P < .05). In the multivariable model, only history of brain tumor (odds ratio [OR] 5.88, 95% confidence interval [CI], 1.33-26.1) and head trauma as a result of seizure (OR 3.92, 95% CI, 1.01-15.2) reached statistical significance in predicting an acutely abnormal scan. The likelihood of an acute imaging abnormality in visits for patients without a history of brain tumor or head trauma as a result of the seizure was 2.7% (2 visits). Both of these patients had abnormal neurological examinations.ConclusionObtaining an emergent CT scan for patients with epilepsy presenting with a seizure may be avoidable in most cases, but might be indicated for patients with a history of brain tumor or head trauma as a result of seizure.

BACKGROUND:Delirium affects more than seven million hospitalized adults in the United States annually. However, its impact on postdischarge healthcare utilization remains unclear. OBJECTIVE:To determine the association between delirium and 30-day hospital readmission. DESIGN:A retrospective cohort study. SETTING:A general community medical and surgical hospital. PATIENTS:All adults who were at least 65 years old, without a history of delirium or alcohol-related delirium, and were hospitalized from September 2010 to March 2015. MEASUREMENTS:The patients deemed at risk for or displaying symptoms of delirium were screened by nurses using the Confusion Assessment Method with a followup by a staff psychiatrist for a subset of screen-positive patients. Patients with delirium confirmed by a staff psychiatrist were compared with those without delirium. The primary outcome was the 30-day readmission rate. The secondary outcomes included emergency department (ED) visits 30 days postdischarge, mortality during hospitalization and 30 days postdischarge, and discharge location. RESULTS:The cohort included 718 delirious patients and 7,927 nondelirious patients. Using an unweighted multivariable logistic regression, delirium was determined to be significantly associated with the increased odds of readmission within 30 days of discharge (odds ratio (OR): 2.60; 95% CI, 1.96-3.44; P < .0001). Delirium was also significantly (P < .0001) associated with ED visits within 30 days postdischarge (OR: 2.18; 95% CI: 1.77-2.69) and discharge to a facility (OR: 2.52; 95% CI: 2.09-3.01). CONCLUSIONS:Delirium is a significant predictor of hospital readmission, ED visits, and discharge to a location other than home. Delirious patients should be targeted to reduce postdischarge healthcare utilization.

Objective: Training clinician–scientists is a primary objective of many academic neurology departments, as these individuals are uniquely positioned to perform insightful clinical or laboratory‐based research informed both by clinical knowledge and their own experiences caring for patients. Despite its importance, training clinician–scientists has perhaps never been so challenging. The National Institute of Neurologic Disorders and Stroke (NINDS) R25 program was designed in an attempt to support these individuals, decrease the time needed to obtain National Institutes of Health K awards, and to help educate a cohort of trainees preparing for a career in academic neurology. We endeavored to describe the structure and features of the program while examining its outcomes. Methods: R25 outcome data from 2009 to 2024 were reviewed. Statistical comparisons were made using 2‐sided Mann–Whitney U testing. Results: A total of 67% of adult neurologists who received an R25 had a successful application for a National Institutes of Health K award compared with 45% of adult neurologists who had not received R25 support (p < 0.0001). Among child neurologists, 73% who applied went on to receive K funding after R25 support, compared with 45% who had not been part of the R25 program (p < 0.001). The average time between completion of residency and obtaining a K award for R25 participants was decreased by 26 months among those with an MD/PhD degree, and 32 months for those with an MD degree compared with non‐R25 individuals. Interpretation: The R25 program has been successful in achieving its training goals, but stands as only one component of support for aspiring clinician–scientists. Investments and commitments made by academic neurology departments are key to supporting this success. ANN NEUROL 2024;96:625–632 [ABSTRACT FROM AUTHOR]

ImportanceIdentifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.ObjectiveTo present a case series of patients with diagnostically challenging subacute or chronic meningitis using metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) supported by a statistical framework generated from mNGS of control samples from the environment and from patients who were noninfectious.Design, setting, and participantsIn this case series, mNGS data obtained from the CSF of 94 patients with noninfectious neuroinflammatory disorders and from 24 water and reagent control samples were used to develop and implement a weighted scoring metric based on z scores at the species and genus levels for both nucleotide and protein alignments to prioritize and rank the mNGS results. Total RNA was extracted for mNGS from the CSF of 7 participants with subacute or chronic meningitis who were recruited between September 2013 and March 2017 as part of a multicenter study of mNGS pathogen discovery among patients with suspected neuroinflammatory conditions. The neurologic infections identified by mNGS in these 7 participants represented a diverse array of pathogens. The patients were referred from the University of California, San Francisco Medical Center (n = 2), Zuckerberg San Francisco General Hospital and Trauma Center (n = 2), Cleveland Clinic (n = 1), University of Washington (n = 1), and Kaiser Permanente (n = 1). A weighted z score was used to filter out environmental contaminants and facilitate efficient data triage and analysis.Main outcomes and measuresPathogens identified by mNGS and the ability of a statistical model to prioritize, rank, and simplify mNGS results.ResultsThe 7 participants ranged in age from 10 to 55 years, and 3 (43%) were female. A parasitic worm (Taenia solium, in 2 participants), a virus (HIV-1), and 4 fungi (Cryptococcus neoformans, Aspergillus oryzae, Histoplasma capsulatum, and Candida dubliniensis) were identified among the 7 participants by using mNGS. Evaluating mNGS data with a weighted z score-based scoring algorithm reduced the reported microbial taxa by a mean of 87% (range, 41%-99%) when taxa with a combined score of 0 or less were removed, effectively separating bona fide pathogen sequences from spurious environmental sequences so that, in each case, the causative pathogen was found within the top 2 scoring microbes identified using the algorithm.Conclusions and relevanceDiverse microbial pathogens were identified by mNGS in the CSF of patients with diagnostically challenging subacute or chronic meningitis, including a case of subarachnoid neurocysticercosis that defied diagnosis for 1 year, the first reported case of CNS vasculitis caused by Aspergillus oryzae, and the fourth reported case of C dubliniensis meningitis. Prioritizing metagenomic data with a scoring algorithm greatly clarified data interpretation and highlighted the problem of attributing biological significance to organisms present in control samples used for metagenomic sequencing studies.

BackgroundDelirium is a frequent and detrimental complication of inpatient hospitalization. Multicomponent intervention in selected groups has been shown to prevent and treat delirium, though little data exists on the effect of intervention in neurological patients. We studied the efficacy of a multicomponent delirium care pathway implemented on a largely neurology and neurosurgery hospital ward among unselected patients.MethodsWe incorporated a multicomponent delirium care pathway into the workflow of a university hospital for patients older than 50 years. The pathway involved risk-stratification for development of delirium, delirium screening, and non-pharmacologic behavioral prevention and intervention. We then retrospectively reviewed admissions before and after implementation of the care pathway. Our primary endpoint was incidence of delirium; secondary endpoints included delirium days, length of stay, restraint use, readmission rates, and discharge disposition.ResultsSeven hundred ninety eight admissions from before the delirium care pathway went into effect and 797 admissions from afterwards were reviewed. Baseline characteristics between groups were similar. Delirium incidence between the two groups did not change (7.0% before vs 7.2% after, p = 0.89). Length of stay among delirious patients significantly decreased after implementation of the delirium care pathway (9.60 before vs 7.06 after, β = - 0.16, adjusted p-value = 0.001).ConclusionImplementation of a delirium care pathway on a neurosciences ward was not associated with changes in the rate of delirium development, though length of stay among delirious patients decreased. In a largely neurologic population, multicomponent intervention to prevent and treat delirium may not change delirium incidence, but may be effective in mitigating delirium complications.

ObjectiveThe mechanism of hypoglycorrhachia-low CSF glucose-in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels.MethodsWe retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis.ResultsWe found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial (R2 = 36%, p < 0.001) and repeated CSF sampling (R2 = 46%, p < 0.001). Hypoglycorrhachia (

IntroductionReducing unplanned hospital readmissions has become a national focus due to the Centers for Medicare and Medicaid Services' (CMS) penalties for hospitals with high rates. A first step in reducing unplanned readmission is to understand which patients are at high risk for readmission, which readmissions are planned, and how well planned readmissions are currently captured in comparison to patient-level chart review.MethodsWe examined all 5455 inpatient neurology admissions over a 2-year period to University of California San Francisco Medical Center and Johns Hopkins Hospital via chart review. We collected information such as patient age, procedure codes, diagnosis codes, all-payer diagnosis-related group, observed length of stay (oLOS), and expected length of stay. We performed multivariate logistic modeling to determine predictors of readmission. Discharge summaries were reviewed for evidence that a subsequent readmission was planned.ResultsA total of 353 (6.5%) discharges were readmitted within 30 days. Fifty-five (15.6%) of the 353 readmissions were planned, most often for a neurosurgical procedure (41.8%) or immunotherapy (23.6%). Only 8 of these readmissions would have been classified as planned using current CMS methodology. Patient age (odds ratio [OR] = 1.01 for each 10-year increase, P < .001) and estimated length of stay (OR = 1.04, P = .002) were associated with a greater likelihood of readmission, whereas index admission oLOS was not.ConclusionsMany neurologic readmissions are planned; however, these are often classified by current CMS methodology as unplanned and penalized accordingly. Modifications of the CMS lists for potentially planned neurological and neurosurgical procedures and for acute discharge neurologic diagnoses should be considered.

Levamisole is a common adulterant in cocaine and has previously been associated with a variety of serious complications including multifocal inflammatory leukoencephalopathy (MIL). There have been several reports of MIL in patients taking cocaine and, though suspected, the presence of levamisole was not confirmed. We present a case of a 63-year-old woman presenting with stupor and spastic quadraparesis found to have urine positive for cocaine and levamisole. An MRI brain revealed innumerable FLAIR hyperintensities with restricted diffusion and incomplete ring-enhancement. This is the first case to confirm the presence of levamisole in a patient with MIL associated with cocaine use.

There is urgent need for clinical trials of novel interventions to reduce the burden of acute ischemic stroke. A key impediment to such trials is slow recruitment. Since obtaining written informed consent in the setting of acute stroke is especially challenging, some experts have endorsed relaxing the requirement for informed consent by permitting verbal consent or waivers to facilitate recruitment. This systematic review of 36 randomized controlled trials of acute interventions for ischemic stroke assesses whether alternatives to written informed consent are associated with increased recruitment rates. After the exclusion of 2 outlier trials that differed from other trials in conduct and interventions studied, no association was observed on univariable analysis (8.9 participants/month in trials requiring written consent vs 6.1 participants/month in trials with alternatives, p = 0.43) or multivariable analysis (when adjusting for the number of centers, number of countries, and exclusions based on modified Rankin Scale scores). Alternatives to written informed consent in acute stroke trials may enable trial designs that would not be feasible otherwise. However, we did not find evidence that, within traditional trial designs, such alternatives are associated with faster recruitment.

Transitions of care have emerged as an important point of vulnerability in the health care system where medical errors and clinical deterioration can occur. Most research in the area has focused on non-neurologically ill patients in the postdischarge transition from the inpatient to outpatient clinical environment in part due to the emergence of hospital readmissions reduction programs. A multidisciplinary strategy that addresses several common opportunities for improvement can mitigate the risk to patients during these periods and can serve as an opportunity for neurologists to take the lead in developing systems-based solutions that can ultimately enhance the quality of care for our patients.

Background and purposeMedicine hospitalist programs have effectively incorporated hospitalist-run discharge clinics into clinical practice to help bridge the vulnerable transition periods after hospital discharge. A neurohospitalist discharge clinic would similarly allow continuity with the inpatient provider while addressing challenges in the coordination of neurologic care. We anticipated that this would afford a greater total number of patients to be seen and at a shorter interval.MethodsThe number of posthospital discharge patients who were seen in general continuity per month in the 6 months prior to establishment of neurohospitalist discharge clinic and those seen over 1 full calendar year 6 months after clinic began was compared by reviewing medical records. Average length of time between discharge from hospital and first clinic visit was compared between patients seen in general neurology continuity clinic and those seen in discharge clinic.ResultsThere was a significant increase in the average number of postdischarge visits per month after initiation of neurohospitalist discharge clinic compared to prior (16.1 visits vs 10.5 visits, P = .001). Patients were seen significantly sooner after hospitalization in discharge clinic (35.9 ± 4.3 days) compared to those seen in general continuity clinic during the same time epoch (57.6 ± 4.1 days; p < 0.001).ConclusionsCreation of a neurohospitalist discharge clinic was effective in increasing posthospital discharge follow-up frequency and shortening duration of time to follow-up.

Ischemic stroke is a leading cause of death and disability worldwide. Recent advances in acute treatment provide hope that the impact of this disease will be reduced. Rapid assessment for large vessel occlusion is now a key element in acute stroke care given advances in endovascular therapy. Because access to acute therapies is limited, development of systems of care to triage appropriate patients to specialized centers is essential. Acute hospitalization management requires multiple strategies including initiation of secondary prevention measures. In addition to preventing further stroke, physicians can also improve long-term survival by preventing the complications of stroke in the hospital and ensuring longitudinal poststroke care and rehabilitation following discharge.

Dementia is an important risk factor for delirium, but the optimal strategy for incorporating cognitive impairment into delirium risk assessment at the time of hospital admission is unknown. We compared 2 informant-based screening tools for dementia and mild cognitive impairment [AD8 and D=(MC)] to the Mini Mental State Examination (MMSE) and Mini-cog in predicting hospital-acquired delirium. This prospective cohort study at an academic medical center consisted of 162 medical inpatients over age 50 years without delirium upon admission. Each participant was evaluated using the MMSE, Mini-cog, AD8, and D=(MC) upon admission and was assessed daily for delirium. An MMSE≤24 carried a 5.5 [95% confidence intervals (CI), 2.7-11.1] relative risk for delirium, whereas cognitive impairment detected by the Mini-cog, D=(MC), or AD8 carried a 2-fold risk. Adding the D=(MC) to the MMSE increased the sensitivity for predicting delirium from 52% (range, 32% to 73%) for the MMSE alone to 65% (range, 46% to 85%) if either test was positive. If both were positive, specificity was maximized at 97% (range, 94% to 100%), but sensitivity was 17% (range, 2% to 33%). The MMSE and Mini-cog identify a large proportion of patients at risk for hospital-acquired delirium, but the combination of performance-based and an informant-based screens may maximize specificity and sensitivity.

BackgroundPatients admitted to an intensive care unit (ICU) with a primary neurologic disorder often receive multiple radiation-based diagnostic studies of the head and neck. Although radiation exposure puts them at risk of intracranial and neck tumors, the amount of radiation received is largely unknown.MethodsWe sought to accurately collect cumulative radiation exposure data from radiation-based studies in a retrospective cohort of patients admitted to the neuroscience ICU (NICU) at a single institution. Radiation doses of studies were converted to estimated effective doses in mSv via literature-published formulas. To impact ordering practices, we piloted an educational initiative on patient radiation exposure to a cohort of physicians caring for patients with a diagnosis of acute subarachnoid hemorrhage. Patients were randomized to have radiation exposure data posted at the bedside for physician viewing.ResultsWe identified 641 patients from July 2010 to March 2011 who had received at least 1 computed tomography-based study of the head. Patients received on average 18.4 mSv of radiation from head and neck imaging. Patients with subarachnoid hemorrhage received the highest average levels of radiation exposure (37.1 mSv). Attributable risk of carcinogenesis was estimated to be low. A pilot educational initiative did not reduce the total estimated effective dose per patient.ConclusionsAccurate reporting of estimated effective doses for NICU patients is feasible and can be provided to ordering physicians to assist with clinical decision making and potentially lower exposure risk. Further strategies are needed to reduce unnecessary radiation exposure at the physician ordering level.

ObjectiveSome have argued that physicians should not presume to make thrombolysis decisions for incapacitated patients with acute ischemic stroke because the risks and benefits of thrombolysis involve deeply personal values. We evaluated the influence of the inability to consent and of personal health-related values on older adults' emergency treatment preferences for both ischemic stroke and cardiac arrest.MethodsA total of 2,154 US adults age ≥50 years read vignettes in which they had either suffered an acute ischemic stroke and could be treated with thrombolysis, or had suffered a sudden cardiac arrest and could be treated with cardiopulmonary resuscitation. Participants were then asked (1) whether they would want the intervention, or (2) whether they would want to be given the intervention even if their informed consent could not be obtained. We elicited health-related values as predictors of these judgments.ResultsOlder adults were as likely to want stroke thrombolysis when unable to consent (78.1%) as when asked directly (76.2%), whereas older adults were more likely to want cardiopulmonary resuscitation when unable to consent (83.6% compared to 75.9%). Greater confidence in the medical system and reliance on statistical information in decision making were both associated with desiring thrombolysis.InterpretationOlder adults regard thrombolysis no less favorably when considering a situation in which they are unable to consent. These findings provide empirical support for recent professional society recommendations to treat ischemic stroke with thrombolysis in appropriate emergency circumstances under a presumption of consent.

BackgroundIn December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified.MethodsA public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology.ResultsTwo additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor's serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified.ConclusionsClinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients.

Central nervous system (CNS) lymphoma can present a diagnostic challenge. Currently, there is no consensus regarding what presurgical evaluation is warranted or how to proceed when lesions are not surgically accessible. We conducted a review of the literature on CNS lymphoma diagnosis (1966 to October 2011) to determine whether a common diagnostic algorithm can be generated. We extracted data regarding the usefulness of brain and body imaging, serum and cerebrospinal fluid (CSF) studies, ophthalmologic examination, and tissue biopsy in the diagnosis of CNS lymphoma. Contrast enhancement on imaging is highly sensitive at the time of diagnosis: 98.9% in immunocompetent lymphoma and 96.1% in human immunodeficiency virus-related CNS lymphoma. The sensitivity of CSF cytology is low (2%-32%) but increases when combined with flow cytometry. Cerebrospinal fluid lactate dehydrogenase isozyme 5, β2-microglobulin, and immunoglobulin heavy chain rearrangement studies have improved sensitivity over CSF cytology (58%-85%) but have only moderate specificity (85%). New techniques of proteomics and microRNA analysis have more than 95% specificity in the diagnosis of CNS lymphoma. Positive CSF cytology, vitreous biopsy, or brain/leptomeningeal biopsy remain the current standard for diagnosis. A combined stepwise systematic approach outlined here may facilitate an expeditious, comprehensive presurgical evaluation for cases of suspected CNS lymphoma.

Background and purposeDizziness is a frequent reason for neuroimaging and neurological consultation, but little is known about the utility of either practice. We sought to characterize the patterns and yield of neuroimaging and neurological consultation for dizziness in the emergency department (ED).MethodsWe retrospectively identified consecutive adults presenting to an academic ED from 2007 to 2009, with a primary complaint of dizziness, vertigo, or imbalance. Neurologists reviewed medical records to determine clinical characteristics, whether a neuroimaging study (head computed tomography [CT] or brain magnetic resonance imaging [MRI]) or neurology consultation was obtained in the ED, and to identify relevant findings on neuroimaging studies. Two neurologists assigned a final diagnosis for the cause of dizziness. Logistic regression was used to evaluate bivariate and multivariate predictors of neuroimaging and consultation.ResultsOf 907 dizzy patients (mean age 59 years; 58% women), 321 (35%) had a neuroimaging study (28% CT, 11% MRI, and 4% both) and 180 (20%) had neurological consultation. Serious neurological disease was ultimately diagnosed in 13% of patients with neuroimaging and 21% of patients with neurological consultation, compared to 5% of the overall cohort. Headache and focal neurological deficits were associated with both neuroimaging and neurological consultation, while age ≥60 years and prior stroke predicted neuroimaging but not consultation, and positional symptoms predicted consultation but not neuroimaging.ConclusionIn a tertiary care ED, neuroimaging and neurological consultation were frequently utilized to evaluate dizzy patients, and their diagnostic yield was substantial.

ObjectiveThis study explores the provision of spiritual care by healthcare professionals working at the end of life.DesignQualitative-ethnographic inquiry.SettingPhase 1: five Canadian sites; phase 2: a residential hospice in Alberta, Canada.ParticipantsPhase 1: six palliative care leaders; phase 2: 24 frontline palliative care clinicians.ResultsData were collected over a 12-month period with analysis of findings occurring concurrently. Using semistructured interviews and participant observation, 11 themes, organised under five overarching categories, emerged from the data. Five bedside skills were identified as essential to spiritual care: hearing, sight, speech, touch and presence. The integration of these bedside skills with the intrinsic qualities of healthcare professionals, including their values and spiritual beliefs, appeared to be essential to their application in spiritual care. Spiritual care primarily involved the tacit qualities of healthcare professionals and their effect on patient's spiritual well-being, rather than their explicit technical skill set or expert knowledge base.ConclusionParticipants identified spiritual care as both a specialised care domain and as a philosophy of care that informs and is embedded within physical and psychosocial care. Hearing, sight, speech, touch and presence were identified as the means by which healthcare professionals impacted patients' spiritual well-being regardless of clinician's awareness or intent. An empirical framework is presented providing clinicians with a pragmatic way of incorporating spiritual care into clinical practice.