Spinal epidural arteriovenous fistula with nerve root enhancement mimicking myeloradiculitis: a case report.

BACKGROUND: Gadolinium enhancement of spinal nerve roots on magnetic resonance imaging (MRI) has rarely been reported in spinal dural arteriovenous fistula (SDAVF). Nerve root enhancement and cerebrospinal fluid (CSF) pleocytosis can be deceptive and lead to a misdiagnosis of myeloradiculitis. We report a patient who was initially diagnosed with neurosarcoid myeloradiculitis due to spinal nerve root enhancement, mildly inflammatory cerebrospinal fluid, and pulmonary granulomas, who ultimately was found to have an extensive symptomatic SDAVF. CASE PRESENTATION: A 52-year-old woman presented with a longitudinally extensive spinal cord lesion with associated gadolinium enhancement of the cord and cauda equina nerve roots, and mild lymphocytic pleocytosis. Pulmonary lymph node biopsy revealed non-caseating granulomas and neurosarcoid myeloradiculitis was suspected. She had rapid and profound clinical deterioration after a single dose of steroids. Further work-up with spinal angiography revealed a thoracic SDAVF, which was surgically ligated leading to clinical improvement. CONCLUSIONS: This case highlights an unexpected presentation of SDAVF with nerve root enhancement and concurrent pulmonary non-caseating granulomas, leading to an initial misdiagnosis with neurosarcoidosis. Nerve root enhancement has only rarely been described in cases of SDAVF; however, as this case highlights, it is an important consideration in the differential diagnosis of non-inflammatory causes of longitudinally extensive myeloradiculopathy with nerve root enhancement. This point is highly salient due to the importance of avoiding misdiagnosis of SDAVF, as interventions such as steroids or epidural injections used to treat inflammatory or infiltrative mimics may worsen symptoms in SDAVF. We review the presentation, diagnosis, and management of SDAVF as well as a proposed diagnostic approach to differentiating SDAVF from inflammatory myeloradiculitis.

Fluorescein Angiography Findings in Susac Syndrome: A Multicenter Retrospective Case Series.

BACKGROUND: Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective chart review, we characterize fluorescein angiography (FA) findings and other ancillary studies in Susac syndrome, including the appearance of persistent disease activity and the occurrence of new subclinical disease on FA. METHODS: This multicenter, retrospective case series was institutional review board-approved and included patients with the complete triad of Susac syndrome evaluated with FA, contrasted MRI of the brain, and audiometry from 2010 to 2020. The medical records were reviewed for these ancillary tests, along with demographics, symptoms, visual acuity, visual field defects, and findings on fundoscopy. Clinical relapse was defined as any objective evidence of disease activity during the follow-up period after initial induction of clinical quiescence. The main outcome measure was the sensitivity of ancillary testing, including FA, MRI, and audiometry, to detect relapse. RESULTS: Twenty of the 31 (64%) patients had the complete triad of brain, retinal, and vestibulocochlear involvement from Susac syndrome and were included. Median age at diagnosis was 43.5 years (range 21-63), and 14 (70%) were women. Hearing loss occurred in 20 (100%), encephalopathy in 13 (65%), vertigo in 15 (75%), and headaches in 19 (95%) throughout the course of follow-up. Median visual acuity at both onset and final visit was 20/20 in both eyes. Seventeen (85%) had BRAO at baseline, and 10 (50%) experienced subsequent BRAO during follow-up. FA revealed nonspecific leakage from previous arteriolar damage in 20 (100%), including in patients who were otherwise in remission. Of the 11 episodes of disease activity in which all testing modalities were performed, visual field testing/fundoscopy was abnormal in 4 (36.4%), MRI brain in 2 (18.2%), audiogram in 8 (72.7%), and FA in 9 (81.8%). CONCLUSIONS: New leakage on FA is the most sensitive marker of active disease. Persistent leakage represents previous damage, whereas new areas of leakage suggest ongoing disease activity that requires consideration of modifying immunosuppressive therapy.

COVID-19 severity and age increase the odds of delirium in hospitalized adults with confirmed SARS-CoV-2 infection: a cohort study.

BACKGROUND: Despite recognition of the neurologic and psychiatric complications associated with SARS-CoV-2 infection, the relationship between coronavirus disease 19 (COVID-19) severity on hospital admission and delirium in hospitalized patients is poorly understood. This study sought to measure the association between COVID-19 severity and presence of delirium in both intensive care unit (ICU) and acute care patients by leveraging an existing hospital-wide systematic delirium screening protocol. The secondary analyses included measuring the association between age and presence of delirium, as well as the association between delirium and safety attendant use, restraint use, discharge home, and length of stay. METHODS: In this single center retrospective cohort study, we obtained electronic medical record (EMR) data using the institutional Epic Clarity database to identify all adults diagnosed with COVID-19 and hospitalized for at least 48-h from February 1-July 15, 2020. COVID-19 severity was classified into four groups. These EMR data include twice-daily delirium screenings of all patients using the Nursing Delirium Screening Scale (non-ICU) or CAM-ICU (ICU) per existing hospital-wide protocols. RESULTS: A total of 99 patients were diagnosed with COVID-19, of whom 44 patients required ICU care and 17 met criteria for severe disease within 24-h of admission. Forty-three patients (43%) met criteria for delirium at any point in their hospitalization. Of patients with delirium, 24 (56%) were 65 years old or younger. After adjustment, patients meeting criteria for the two highest COVID-19 severity groups within 24-h of admission had 7.2 times the odds of having delirium compared to those in the lowest category [adjusted odds ratio (aOR) 7.2; 95% confidence interval (CI) 1.9, 27.4; P = 0.003]. Patients > 65 years old had increased odds of delirium compared to those < 45 years old (aOR 8.7; 95% CI 2.2, 33.5; P = 0.003). Delirium was associated with increased odds of safety attendant use (aOR 4.5; 95% CI 1.0, 20.7; P = 0.050), decreased odds of discharge home (aOR 0.2; 95% CI 0.06, 0.6; P = 0.005), and increased length of stay (aOR 7.5; 95% CI 2.0, 13; P = 0.008). CONCLUSIONS: While delirium is common in hospitalized patients of all ages with COVID-19, it is especially common in those with severe disease on hospital admission and those who are older. Patients with COVID-19 and delirium, compared to COVID-19 without delirium, are more likely to require safety attendants during hospitalization, less likely to be discharged home, and have a longer length of stay. Individuals with COVID-19, including younger patients, represent an important population to target for delirium screening and management as delirium is associated with important differences in both clinical care and disposition.

Postoperative delirium prediction using machine learning models and preoperative electronic health record data.

BACKGROUND: Accurate, pragmatic risk stratification for postoperative delirium (POD) is necessary to target preventative resources toward high-risk patients. Machine learning (ML) offers a novel approach to leveraging electronic health record (EHR) data for POD prediction. We sought to develop and internally validate a ML-derived POD risk prediction model using preoperative risk features, and to compare its performance to models developed with traditional logistic regression. METHODS: This was a retrospective analysis of preoperative EHR data from 24,885 adults undergoing a procedure requiring anesthesia care, recovering in the main post-anesthesia care unit, and staying in the hospital at least overnight between December 2016 and December 2019 at either of two hospitals in a tertiary care health system. One hundred fifteen preoperative risk features including demographics, comorbidities, nursing assessments, surgery type, and other preoperative EHR data were used to predict postoperative delirium (POD), defined as any instance of Nursing Delirium Screening Scale ≥2 or positive Confusion Assessment Method for the Intensive Care Unit within the first 7 postoperative days. Two ML models (Neural Network and XGBoost), two traditional logistic regression models ("clinician-guided" and "ML hybrid"), and a previously described delirium risk stratification tool (AWOL-S) were evaluated using the area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, positive likelihood ratio, and positive predictive value. Model calibration was assessed with a calibration curve. Patients with no POD assessments charted or at least 20% of input variables missing were excluded. RESULTS: POD incidence was 5.3%. The AUC-ROC for Neural Net was 0.841 [95% CI 0. 816-0.863] and for XGBoost was 0.851 [95% CI 0.827-0.874], which was significantly better than the clinician-guided (AUC-ROC 0.763 [0.734-0.793], p < 0.001) and ML hybrid (AUC-ROC 0.824 [0.800-0.849], p < 0.001) regression models and AWOL-S (AUC-ROC 0.762 [95% CI 0.713-0.812], p < 0.001). Neural Net, XGBoost, and ML hybrid models demonstrated excellent calibration, while calibration of the clinician-guided and AWOL-S models was moderate; they tended to overestimate delirium risk in those already at highest risk. CONCLUSION: Using pragmatically collected EHR data, two ML models predicted POD in a broad perioperative population with high discrimination. Optimal application of the models would provide automated, real-time delirium risk stratification to improve perioperative management of surgical patients at risk for POD.

An Implementation-Effectiveness Study of a Perioperative Delirium Prevention Initiative for Older Adults.

BACKGROUND: Postoperative delirium is a common and serious problem for older adults. To better align local practices with delirium prevention consensus guidelines, we implemented a 5-component intervention followed by a quality improvement (QI) project at our institution. METHODS: This hybrid implementation-effectiveness study took place at 2 adult hospitals within a tertiary care academic health care system. We implemented a 5-component intervention: preoperative delirium risk stratification, multidisciplinary education, written memory aids, delirium prevention postanesthesia care unit (PACU) orderset, and electronic health record enhancements between December 1, 2017 and June 30, 2018. This was followed by a department-wide QI project to increase uptake of the intervention from July 1, 2018 to June 30, 2019. We tracked process outcomes during the QI period, including frequency of preoperative delirium risk screening, percentage of "high-risk" screens, and frequency of appropriate PACU orderset use. We measured practice change after the interventions using interrupted time series analysis of perioperative medication prescribing practices during baseline (December 1, 2016 to November 30, 2017), intervention (December 1, 2017 to June 30, 2018), and QI (July 1, 2018 to June 30, 2019) periods. Participants were consecutive older patients (≥65 years of age) who underwent surgery during the above timeframes and received care in the PACU, compared to a concurrent control group <65 years of age. The a priori primary outcome was a composite of perioperative American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use (Beers PIM) medications. The secondary outcome, delirium incidence, was measured in the subset of older patients who were admitted to the hospital for at least 1 night. RESULTS: During the 12-month QI period, preoperative delirium risk stratification improved from 67% (714 of 1068 patients) in month 1 to 83% in month 12 (776 of 931 patients). Forty percent of patients were stratified as "high risk" during the 12-month period (4246 of 10,494 patients). Appropriate PACU orderset use in high-risk patients increased from 19% in month 1 to 85% in month 12. We analyzed medication use in 7212, 4416, and 8311 PACU care episodes during the baseline, intervention, and QI periods, respectively. Beers PIM administration decreased from 33% to 27% to 23% during the 3 time periods, with adjusted odds ratio (aOR) 0.97 (95% confidence interval [CI], 0.95-0.998; P = .03) per month during the QI period in comparison to baseline. Delirium incidence was 7.5%, 9.2%, and 8.5% during the 3 time periods with aOR of delirium of 0.98 (95% CI, 0.91-1.05, P = .52) per month during the QI period in comparison to baseline. CONCLUSIONS: A perioperative delirium prevention intervention was associated with reduced administration of Beers PIMs to older adults.

Whole-Genome mRNA Gene Expression Differs Between Patients With and Without Delirium.

OBJECTIVE: To identify differences in gene expression between patients with in-hospital delirium from a known etiology (urinary tract infection [UTI]) and patients with delirium from an unknown etiology, as well as from nondelirious patients. METHODS: Thirty patients with delirium (8 with UTI) and 21 nondelirious patients (11 with UTI) were included in this prospective case-control study. Transcriptomic profiles from messenger RNA sequencing of peripheral blood were analyzed for gene expression and disease-specific pathway enrichment patterns, correcting for systemic inflammatory response syndrome. Genes and pathways with significant differential activity based on Fisher exact test ( P < .05, |Z score| >2) are reported. RESULTS: Patients with delirium with UTI, compared to patients with delirium without UTI, exhibited significant activation of interferon signaling, upstream cytokines, and transcription regulators, as well as significant inhibition of actin cytoskeleton, integrin, paxillin, glioma invasiveness signaling, and upstream growth factors. All patients with delirium, compared to nondelirious patients, had significant complement system activation. Among patients with delirium without UTI, compared to nondelirious patients without UTI, there was significant activation of elF4 and p7056 K signaling. CONCLUSIONS: Differences exist in gene expression between delirious patients due to UTI presence, as well as due to the presence of delirium alone. Transcriptional profiling may help develop etiology-specific biomarkers for patients with delirium.

Evaluation of a multicomponent pathway to address inpatient delirium on a neurosciences ward.

BACKGROUND: Delirium 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. METHODS: We 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. RESULTS: Seven 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, ß = - 0.16, adjusted p-value = 0.001). CONCLUSION: Implementation 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.

Predicting inpatient delirium: The AWOL delirium risk-stratification score in clinical practice.

Inpatient delirium improves with multicomponent interventions by hospital staff, though the resources needed are often limited. Risk-stratification to predict delirium is a useful first step to help triage resources, but the performance of risk-stratification as part of a functioning multicomponent pathway has not been assessed. We retrospectively studied the performance of a validated delirium prediction rule, the AWOL score, as a part of a multicomponent delirium care pathway in practice on a university hospital ward. We reviewed the hospitalizations of patients 50 years or older for evidence of delirium and extracted the AWOL score from nursing documentation (n = 347). The area under the receiver operating characteristic curve (AUC) was 0.83 (95% CI 0.77-0.89) for all cases and 0.73 (95% CI 0.60-0.85) when cases of prevalent delirium were removed. Involving minimal additional assessment, this nursing-based risk stratification score performed well as part of a multicomponent delirium care pathway.

Moving Beyond Metabolic Encephalopathy: An Update on Delirium Prevention, Workup, and Management.

Delirium is a condition that frequently complicates hospitalization and consists of an acute decline in orientation and attention, often accompanied by other cognitive changes. Delirium is tied to multiple detrimental outcomes both in the short and long term, including cognitive and functional decline, inpatient complications, and mortality. Postoperative, elderly medical, and critical care patients have been identified as populations at particular risk. In this review, the authors discuss current theories on pathophysiology, recommended workup, and evidence-based prevention and management of inpatient delirium. In general, instituting a system of active screening of at-risk populations and nonpharmacologic interventions for prevention and treatment seems to be the most effective method of addressing delirium. More research is needed to clarify the etiology of delirium and develop safe therapeutic options that address the underlying pathophysiology.

A Prospective Comparison of Informant-based and Performance-based Dementia Screening Tools to Predict In-Hospital Delirium.

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.

Adult-onset central nervous system hemophagocytic lymphohistiocytosis: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome with both genetic and acquired causes characterized by elevated cytokine levels, hyperinflammation, and overactivation of lymphocytes and macrophages. It is typically a systemic disease with variable degrees of CNS involvement. Cases with predominantly central nervous system (CNS) involvement are very rare, with the vast majority of these occurring in infants and young children. This report documents a case of adult-onset CNS-HLH involving a middle-aged man. CASE PRESENTATION: A 55 year-old man developed progressive left hemiparesis and aphasia over the course of several months. Brain MRI showed multifocal, mass-like enhancing lesions with increased susceptibility consistent with blood products. An extensive workup for infectious, autoimmune, and neoplastic etiologies was significant only for a markedly elevated serum ferritin at 1456 ng/mL. Two brain biopsies showed a non-specific inflammatory process. The patient was treated empirically with steroids and plasmapheresis, but he continued to suffer a progressive neurological decline and died one year after onset of neurological symptoms. Autopsy revealed profound histiocytic infiltration, perivascular lymphocytosis, and emperipolesis, compatible with CNS-HLH. CONCLUSION: This case report describes an exceedingly rare presentation of an adult patient with CNS predominant HLH. This diagnosis should be considered in the differential diagnosis of adults presenting with progressive brain lesions, even in the absence of typical systemic signs of HLH.

Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Diagnostic yield of electroencephalography in the medical and surgical intensive care unit.

BACKGROUND: To determine the incidence of electrographic seizures during continuous electroencephalography (cEEG) in the medical and surgical ICU. METHODS: We retrospectively reviewed the records of all adults who underwent cEEG in our medical and surgical ICU over a 4.5 year period. Patients with acute brain injury were excluded. Our primary outcome was cEEG documentation of an electrographic seizure, defined as a rhythmic discharge or spike and wave pattern demonstrating definite evolution and lasting at least 10 s. To assess inter-rater variability in cEEG interpretation, two electrophysiologists independently reviewed all available cEEGs of subjects with electrographic seizures documented on their clinical cEEG report and those of an equal number of randomly selected subjects from the remaining cohort. RESULTS: Kappa analysis showed a value of 0.88, indicating excellent inter-rater agreement. Electrographic seizures were identified in 12 of 105 patients (11 %, 95 % CI 5-18 %). This rate did not change after excluding patients with a history of seizure, remote brain injury, or seizure-like events before cEEG. In an ordinal logistic regression model controlling for age, sex, and SOFA score, electrographic seizures were associated with lower odds of good outcomes on the Glasgow Outcome Scale at discharge (OR 0.3, 95 % CI 0.1-0.8). CONCLUSION: In a tertiary care medical and surgical ICU, electrographic seizures were seen on 11 % of cEEGs ordered for the evaluation of encephalopathy, and were associated with worse functional outcomes at discharge. Our findings confirm the results of a prior study suggesting a substantial burden of electrographic seizures in critically ill encephalopathic patients.

Potential for remote vital sign monitoring to improve hospital patient sleep: A feasibility study.

BACKGROUND: Even low-acuity patients suffer from disrupted sleep in the hospital in part due to routine overnight vital sign (VS) checks. When invasive monitoring is not needed, vital sign monitoring devices (VSMDs) similar to consumer-grade health monitors may play a role in promoting sleep, which can aid healing and recovery. METHODS: We provided one VSMD to neuroscience ward patients during their hospital stays and used surveys to assess patient and nurse attitudes toward the device and the impact of the device on patient comfort. We also compared VSMD-streamed vS data to nurse-recorded vS data in the chart to evaluate the consistency of data streaming and data concordance between the device and nurse-collected vital sign values. FINDINGS: 21 patients and 15 nurses enrolled. Overall, patients and nurses responded positively to the device and patients preferred wearing the device to receiving manual vital checks overnight. The most common device-related cause of sleep disruption per patients was device weight (29%). Device vS were concordant with nurse vS on average but there was significant variance in agreement between nurse and device values. INTERPRETATION: Patients and nurses feel positively about the use of VSMDs and their use in the hospital. The device we tested may be limited in its sleep promotion by its weight and patient comfort assessment. Further research is needed to assess the precision of the device in measuring vital signs when used in a clinical setting. Future studies should compare VSMD models and assess their impacts on patient sleep in the absence of manual vS checks overnight. FUNDING: Funding provided by the Sara & Evan Williams Foundation Endowed Neurohospitalist Chair at UCSF.

Predisposing and Precipitating Factors Associated With Delirium: A Systematic Review.

Importance: Despite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the attempt to treat all instances of delirium similarly, leaving delirium management as an unmet need. An individualized approach based on unique patterns of delirium pathophysiology, as reflected in predisposing factors and precipitants, may be necessary, but there exists no accepted method of grouping delirium into distinct etiologic subgroups. Objective: To conduct a systematic review to identify potential predisposing and precipitating factors associated with delirium in adult patients agnostic to setting. Evidence Review: A literature search was performed of PubMed, Embase, Web of Science, and PsycINFO from database inception to December 2021 using search Medical Subject Headings (MeSH) terms consciousness disorders, confusion, causality, and disease susceptibility, with constraints of cohort or case-control studies. Two reviewers selected studies that met the following criteria for inclusion: published in English, prospective cohort or case-control study, at least 50 participants, delirium assessment in person by a physician or trained research personnel using a reference standard, and results including a multivariable model to identify independent factors associated with delirium. Findings: A total of 315 studies were included with a mean (SD) Newcastle-Ottawa Scale score of 8.3 (0.8) out of 9. Across 101 144 patients (50 006 [50.0%] male and 49 766 [49.1%] female patients) represented (24 015 with delirium), studies reported 33 predisposing and 112 precipitating factors associated with delirium. There was a diversity of factors associated with delirium, with substantial physiological heterogeneity. Conclusions and Relevance: In this systematic review, a comprehensive list of potential predisposing and precipitating factors associated with delirium was found across all clinical settings. These findings may be used to inform more precise study of delirium's heterogeneous pathophysiology and treatment.

Approach to Altered Mental Status and Inpatient Delirium.

Altered mental status is a nonspecific diagnosis that encompasses a wide spectrum of disease and is frequently cited as a reason for both hospital admission and inpatient neurologic consultation. There are numerous etiologies of altered mental status, and so although many are facile with the workup of this potentially life-threatening entity, it can nevertheless be overwhelming. Our goal was to provide a practical framework embedded in a current, comprehensive review of the epidemiology, clinical evaluation, and management of undifferentiated altered mental status. We pay particular attention to the management of a critical yet underdiagnosed subtype of altered mental status: delirium.

KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients.

Despite the association between cognitive impairment and delirium, little is known about whether genetic differences that confer cognitive resilience also confer resistance to delirium. To investigate whether older adults without postoperative delirium, compared with those with postoperative delirium, are more likely to have specific single nucleotide polymorphisms (SNPs) in the FKBP5, KIBRA, KLOTHO, MTNR1B, and SIRT1 genes known to be associated with cognition or delirium. This prospective nested matched exploratory case-control study included 94 older adults who underwent orthopedic surgery and screened for postoperative delirium. Forty-seven subjects had incident delirium, and 47 age-matched controls were not delirious. The primary study outcome was genotype frequency for the five SNPs. Compared with participants with delirium, those without delirium had higher adjusted odds of KIBRA SNP rs17070145 CT/TT [vs. CC; adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.03, 7.54; p = 0.04] and MTNR1B SNP rs10830963 CG/GG (vs. CC; aOR 4.14, 95% CI 1.36, 12.59; p = 0.01). FKBP5 SNP rs1360780 CT/TT (vs. CC) demonstrated borderline increased adjusted odds of not developing delirium (aOR 2.51, 95% CI 1.00, 7.34; p = 0.05). Our results highlight the relevance of KIBRA, MTNR1B, and FKBP5 in understanding the complex relationship between delirium, cognition, and sleep, which warrant further study in larger, more diverse populations.

Dementia=(MC)2: a 4-item screening test for mild cognitive impairment and dementia.

To develop a practical informant-based screening tool that reliably identifies patients with mild cognitive impairment (MCI) and dementia, we analyzed data from a sample of patients and normal controls seen in a memory clinic. All patients were evaluated with the Clinical Dementia Rating scale. Individual Clinical Dementia Rating responses were dichotomized and entered into a forward stepwise multivariable logistic regression model. Four independent predictors of MCI and dementia thus identified were combined into a prediction rule that was validated in a separate cohort drawn from the same clinic. Using a cut point of 2 or more positive responses to the 4 questions, the final prediction rule had sensitivity of 95% (95% confidence interval (CI): 92-97%) for MCI or dementia, and a specificity of 91% (95% CI: 86-95%). When applied to the validation cohort, the sensitivity for MCI or dementia was 96% (95% CI: 94-98%), and the specificity was 96% (95% CI: 92-98%). Using both cohorts, the positive likelihood ratio for MCI or dementia was 15.6 (95% CI: 14.0-17.3) and the negative likelihood ratio was 0.05 (95% CI: 0.04-0.07). This tool has the potential to identify patients who warrant further cognitive evaluation in busy outpatient or emergency department settings.

Urgent neurology consultation from the ED for transient ischemic attack.

OBJECTIVE: The objective of this study was to evaluate the association between urgent neurology consultation and outcomes for patients with transient ischemic attack (TIA). METHODS: In a secondary analysis of data from 1707 emergency department patients with transient ischemic attack from March 1997 to May 1998, we compared presentation, management, and outcomes by neurology consultation status using generalized estimating equations to adjust for ABCD(2) score and clustering by facility and survival analysis for outcomes. RESULTS: Consultation was obtained f28% of patients. Median ABCD(2) scores were comparable, but consultation was associated with hospital admission (odds ratio, 1.35 [1.02-1.78], P = .04) and use of antithrombotics (odds ratio, 1.88 [1.20-2.93], P = .005). The cumulative stroke risk was significantly lower within 1 week (5.3% versus 7.5%, P = .02) but not at 90 days (9.9% versus 11.0%, P = .21). CONCLUSIONS: Consultation was not targeted to high-risk patients but was associated with some quality of care measures and improved early outcomes; however, improvement in 90-day outcomes was not established.