Development of a core outcome set for quality of life for adults with drug-resistant epilepsy: A multistakeholder Delphi consensus study.

OBJECTIVE: In 2017, the American Academy of Neurology (AAN) convened the AAN Quality Measurement Set working group to define the improvement and maintenance of quality of life (QOL) as a key outcome measure in epilepsy clinical practice. A core outcome set (COS), defined as an accepted, standardized set of outcomes that should be minimally measured and reported in an area of health care research and practice, has not previously been defined for QOL in adult epilepsy. METHODS: A cross-sectional Delphi consensus study was employed to attain consensus from patients and caregivers on the QOL outcomes that should be minimally measured and reported in epilepsy clinical practice. Candidate items were compiled from QOL scales recommended by the AAN 2017 Quality Measurement Set. Inclusion criteria to participate in the Delphi study were adults with drug-resistant epilepsy diagnosed by a physician, no prior diagnosis of psychogenic nonepileptic seizures or a cognitive and/or developmental disability, or caregivers of patients meeting these criteria. RESULTS: A total of 109 people satisfied inclusion/exclusion criteria and took part in Delphi Round 1 (patients, n = 95, 87.2%; caregivers, n = 14, 12.8%), and 55 people from Round 1 completed Round 2 (patients, n = 43, 78.2%; caregivers, n = 12, 21.8%). One hundred three people took part in the final consensus round. Consensus was attained by patients/caregivers on a set of 36 outcomes that should minimally be included in the QOL COS. Of these, 32 of the 36 outcomes (88.8%) pertained to areas outside of seizure frequency and severity. SIGNIFICANCE: Using patient-centered Delphi methodology, this study defines the first COS for QOL measurement in clinical practice for adults with drug-resistant epilepsy. This set highlights the diversity of factors beyond seizure frequency and severity that impact QOL in epilepsy.

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis.

BACKGROUND: Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS: In 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. RESULTS: We 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. CONCLUSIONS: Routine 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.).

Real-World Midazolam Use and Outcomes With Out-of-Hospital Treatment of Status Epilepticus in the United States.

STUDY OBJECTIVE: Guidelines recommend 10-mg intramuscular midazolam as the first-line treatment option for status epilepticus. However, in real-world practice, it is frequently administered intranasally or intravenously and is dosed lower. Therefore, we used conventional and instrumental variable approaches to examine the effectiveness of midazolam in a national out-of-hospital cohort. METHODS: This retrospective cohort study of adults with status epilepticus used the ESO Data Collaborative research dataset (January 1, 2019, to December 31, 2019). The exposures were the route and dose of midazolam. We performed hierarchical logistic regression and 2-stage least squares regression using agency treatment patterns as an instrument to examine our outcomes, rescue therapy, and ventilatory support. RESULTS: There were 7,634 out-of-hospital encounters from 657 EMS agencies. Midazolam was administered intranasally in 20%, intravenously in 46%, and intramuscularly in 35% of the encounters. Compared with intramuscular administration, intranasal midazolam increased (risk difference [RD], 6.5%; 95% confidence interval [CI], 2.4% to 10.5%) and intravenous midazolam decreased (RD, -11.1%; 95% CI, -14.7% to -7.5%) the risk of rescue therapy. The differences in ventilatory support were not statistically significant (intranasal RD, -1.5%; 95% CI, -3.2% to 0.3%; intravenous RD, -0.3%; 95% CI, -1.9% to 1.2%). Higher doses were associated with a lower risk of rescue therapy (RD, -2.6%; 95% CI, -3.3% to -1.9%) and increased ventilatory support (RD, 0.4%; 95% CI, 0.1% to 0.7%). The instrumental variable analysis yielded similar results, except that dose was not associated with ventilatory support. CONCLUSION: The route and dose of midazolam affect clinical outcomes. Compared with intramuscular administration, intranasal administration may be less effective and intravenous administration more effective in terminating status epilepticus, although the differences between these and previous results may reflect the nature of real-world data as opposed to randomized data.

Endovascular embolization versus surgical clipping in a single surgeon series of basilar artery aneurysms: a complementary approach in the endovascular era.

BACKGROUND: Currently, 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. METHODS: Retrospective analysis of prospectively maintained, single-surgeon series of BAAs treated with endovascular or open surgery from the first 5 years of practice. RESULTS: Forty-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. CONCLUSIONS: Complementary 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.

Cocaine Use and White Matter Hyperintensities in Homeless and Unstably Housed Women.

OBJECTIVES: Cocaine 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 METHODS: We 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. RESULTS: Mean 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. CONCLUSIONS: Over 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.

Visualizing wall enhancement over time in unruptured intracranial aneurysms using 3D vessel wall imaging.

BACKGROUND: Few studies directed at assessing the visualization of the walls of unruptured aneurysms have used higher-resolution 3D MRI vessel wall imaging. Prospective longitudinal studies are also needed to screen vessel wall changes in unruptured aneurysms. PURPOSE: To compare the aneurysm wall visualization on pre- and post-3D isotropic T1 -weighted Sampling Perfection with Application-optimized Contrasts by using different flip angle Evolutions (SPACE) images and to explore whether there is a change in wall enhancement at follow up. STUDY TYPE: Prospective. POPULATION: Twenty-nine patients with a total of 35 unruptured intracranial aneurysms. SEQUENCE: 3D T1 -weighted pre- and postcontrast SPACE (0.5 mm isotropic) at 3.0T. ASSESSMENT: The aneurysm wall visibility (0-5 scale) between pre- and postcontrast images as well as the wall enhancement (0-5 scale) between follow-up and baseline studies (6-30 months, average 12.7 months) were compared. Differences in wall visibility and enhancement were also investigated as a function of aneurysm diameter and location. STATISTICAL TEST: The Wilcoxon signed rank paired test was used to compare the wall visibility score between pre- and postcontrast SPACE images, as well as wall enhancement between follow-up and baseline. The Mann-Whitney and Kruskal-Wallis tests were used to investigate the enhancement difference between different diameters and locations. RESULTS: Postcontrast images had significantly higher wall visibility (P = 0.01). A wall enhancement score ≥2 was found in 71% of the aneurysms. Changes in levels of wall enhancement were found in 17% of the aneurysms at follow-up studies, but those changes were small. Wall visibility and enhancement scores of large aneurysms were significantly higher than small ones (P < 0.001). DATA CONCLUSION: 3D T1 -weighted higher resolution SPACE can be used to assess changes in enhancement at follow-up studies. Contrast SPACE image provides better aneurysm wall visibility and improves visualization of the aneurysm wall. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:193-200.

Imaging in neurointerventional stroke treatment: review of the recent trials and what your neurointerventionalist wants to know from emergency radiologists.

Stroke is one of the leading causes of death and disability worldwide. Standard treatment for stroke is intravenous (IV) injection of tissue plasminogen activator (t-PA) rapidly after symptom onset. However, there are limitations of IV t-PA treatment, such as a short time window for administration and risk for hemorrhage. Recent trials have demonstrated the benefit of endovascular treatment when added to standard treatment to improve outcomes for patients. Advanced imaging was utilized in some trials to identify patients with proximal intracranial occlusion to target for endovascular reperfusion therapy, and to exclude patients with large infarct cores or poor collateral circulation who would not be expected to benefit from intervention. This article summarizes the use of imaging in recent stroke trials in details, provides a stroke imaging protocol, and provides tips which radiologists should know to help their neurointerventionalists.

Brain Emboli After Left Ventricular Endocardial Ablation.

BACKGROUND: Catheter ablation for ventricular tachycardia and premature ventricular complexes (PVCs) is common. Catheter ablation of atrial fibrillation is associated with a risk of cerebral emboli attributed to cardioversions and numerous ablation lesions in the low-flow left atrium, but cerebral embolic risk in ventricular ablation has not been evaluated. METHODS: We enrolled 18 consecutive patients meeting study criteria scheduled for ventricular tachycardia or PVC ablation over a 9-month period. Patients undergoing left ventricular (LV) ablation were compared with a control group of those undergoing right ventricular ablation only. Patients were excluded if they had implantable cardioverter defibrillators or permanent pacemakers. Radiofrequency energy was used for ablation in all cases and heparin was administered with goal-activated clotting times of 300 to 400 seconds for all LV procedures. Pre- and postprocedural brain MRI was performed on each patient within a week of the ablation procedure. Embolic infarcts were defined as new foci of reduced diffusion and high signal intensity on fluid-attenuated inversion recovery brain MRI within a vascular distribution. RESULTS: The mean age was 58 years, half of the patients were men, half had a history of hypertension, and the majority had no known vascular disease or heart failure. LV ablation was performed in 12 patients (ventricular tachycardia, n=2; PVC, n=10) and right ventricular ablation was performed exclusively in 6 patients (ventricular tachycardia, n=1; PVC, n=5). Seven patients (58%) undergoing LV ablation experienced a total of 16 cerebral emboli, in comparison with zero patients undergoing right ventricular ablation (P=0.04). Seven of 11 patients (63%) undergoing a retrograde approach to the LV developed at least 1 new brain lesion. CONCLUSIONS: More than half of patients undergoing routine LV ablation procedures (predominately PVC ablations) experienced new brain emboli after the procedure. Future research is critical to understanding the long-term consequences of these lesions and to determining optimal strategies to avoid them.

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.

Quantifying Heuristic Bias: Anchoring, Availability, and Representativeness.

Construct: Authors examined whether a new vignette-based instrument could isolate and quantify heuristic bias. BACKGROUND: Heuristics are cognitive shortcuts that may introduce bias and contribute to error. There is no standardized instrument available to quantify heuristic bias in clinical decision making, limiting future study of educational interventions designed to improve calibration of medical decisions. This study presents validity data to support a vignette-based instrument quantifying bias due to the anchoring, availability, and representativeness heuristics. APPROACH: Participants completed questionnaires requiring assignment of probabilities to potential outcomes of medical and nonmedical scenarios. The instrument randomly presented scenarios in one of two versions: Version A, encouraging heuristic bias, and Version B, worded neutrally. The primary outcome was the difference in probability judgments for Version A versus Version B scenario options. RESULTS: Of 167 participants recruited, 139 enrolled. Participants assigned significantly higher mean probability values to Version A scenario options (M = 9.56, SD = 3.75) than Version B (M = 8.98, SD = 3.76), t(1801) = 3.27, p = .001. This result remained significant analyzing medical scenarios alone (Version A, M = 9.41, SD = 3.92; Version B, M = 8.86, SD = 4.09), t(1204) = 2.36, p = .02. Analyzing medical scenarios by heuristic revealed a significant difference between Version A and B for availability (Version A, M = 6.52, SD = 3.32; Version B, M = 5.52, SD = 3.05), t(404) = 3.04, p = .003, and representativeness (Version A, M = 11.45, SD = 3.12; Version B, M = 10.67, SD = 3.71), t(396) = 2.28, p = .02, but not anchoring. Stratifying by training level, students maintained a significant difference between Version A and B medical scenarios (Version A, M = 9.83, SD = 3.75; Version B, M = 9.00, SD = 3.98), t(465) = 2.29, p = .02, but not residents or attendings. Stratifying by heuristic and training level, availability maintained significance for students (Version A, M = 7.28, SD = 3.46; Version B, M = 5.82, SD = 3.22), t(153) = 2.67, p = .008, and residents (Version A, M = 7.19, SD = 3.24; Version B, M = 5.56, SD = 2.72), t(77) = 2.32, p = .02, but not attendings. CONCLUSIONS: Authors developed an instrument to isolate and quantify bias produced by the availability and representativeness heuristics, and illustrated the utility of their instrument by demonstrating decreased heuristic bias within medical contexts at higher training levels.

Validation of a Nurse-Based Delirium-Screening Tool for Hospitalized Patients.

BACKGROUND: Guidelines recommend daily delirium monitoring of hospitalized patients. Available delirium-screening tools have not been validated for use by nurses among diverse inpatients. OBJECTIVE: We sought to validate the Nursing Delirium-Screening Scale (Nu-DESC) under these circumstances. METHODS: A blinded cross-sectional and quality-improvement study was conducted from August 2015-February 2016. Nurses׳ Nu-DESC scores were compared to delirium diagnosis according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria. A total of 405 consecutive hospitalized patients were included. Nu-DESC-positive (threshold score ≥2) patients were matched with equal numbers of Nu-DESC-negative patients, by sex, age, and nursing unit. Nurses recorded a Nu-DESC score for each patient on every 12-hour shift. A Nu-DESC-blinded evaluator interviewed patients for 2 consecutive days. Delirium diagnosis was determined by physicians using DSM-5 criteria applied to collected research data. Sensitivity and specificity of the Nu-DESC were calculated. In an exploratory analysis, the performance of the Nu-DESC was analyzed with the addition of bedside measures of attention. RESULTS: The sensitivity of the Nu-DESC at a threshold of ≥2 was 42% (95% CI: 33-53%). Specificity was 98% (97-98%). At a threshold of ≥1, sensitivity was 67% (52-80%) and specificity 93% (90-95%). Similar results were found with the addition of attention tasks. CONCLUSION: The Nu-DESC is a specific delirium detection tool, but it is not sensitive at the usually proposed cut point of ≥2. Using a threshold of ≥1 or adding a test of attention increase sensitivity with a minor decrease in specificity.

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.

Reducing Cost and Intravenous Duration of Nicardipine in Intracerebral Hemorrhage Patients via an Interdisciplinary Approach.

BACKGROUND: The mainstay of acute management of intracerebral hemorrhage (ICH) is blood pressure reduction. Intravenous (IV) nicardipine is an effective but costly intervention for blood pressure reduction in the intensive care unit (ICU). Earlier transition to oral (PO) antihypertensive agents may reduce ICU length of stay (LOS) and associated costs. We sought to study the effectiveness of an interdisciplinary intervention to start earlier transition to PO antihypertensives. METHODS: From July 2011 to July 2012, patients with ICH who received IV nicardipine were reviewed and screened for eligibility by an interdisciplinary team including physicians and pharmacists. These patients were compared to a control group 1 year prior to this intervention. The duration of nicardipine treatment (median hours), estimated costs, and ICU LOS were measured. RESULTS: A total of 35 patients and 44 controls were studied. The median hours of IV nicardipine use were significantly decreased from a baseline mean of 118 to 30 hours (P < .001); total cost savings per year was $433,566 ($18,475 per patient). The average LOS remained similar (8.4 versus 8.9 days, P < .990). In a follow-up study 1 year later, after the intervention was no longer used, a sample of 21 consecutive patients was reviewed and the duration of IV nicardipine treatment had increased to a mean of 96 hours. CONCLUSION: A physician and pharmacist-led project to initiate oral antihyperintensive medications earlier was successful in reducing the duration of IV nicardipine treatment in patients with ICH while leading to substantial cost savings.

Inability to consent does not diminish the desirability of stroke thrombolysis.

OBJECTIVE: Some 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. METHODS: A 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. RESULTS: Older 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. INTERPRETATION: Older 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.

CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma.

Establishing the diagnosis of focal brain lesions in patients with unexplained neurologic symptoms represents a challenge. The goal of this study is to provide evidence supporting functional roles for CXC chemokine ligand (CXCL)13 and interleukin (IL)-10 in central nervous system (CNS) lymphomas and to evaluate the utility of each as prognostic and diagnostic biomarkers. We demonstrate for the first time that elevated CXCL13 concentration in cerebrospinal fluid (CSF) is prognostic and that CXCL13 and CXCL12 mediate chemotaxis of lymphoma cells isolated from CNS lymphoma lesions. Expression of the activated form of Janus kinase 1 supported a role for IL-10 in prosurvival signaling. We determined the concentration of CXCL13 and IL-10 in CSF of CNS lymphoma patients and control cohorts including inflammatory and degenerative neurologic disease in a multicenter study involving 220 patients. Bivariate elevated CXCL13 plus IL-10 was 99.3% specific for primary and secondary CNS lymphoma, with sensitivity significantly greater than reference standard CSF tests. These results identify CXCL13 and IL-10 as potentially important biomarkers of CNS lymphoma that merit further evaluation and support incorporation of CXCL13 and IL-10 into diagnostic algorithms for the workup of focal brain lesions in which lymphoma is a consideration.

A Practical Approach to Meningitis and Encephalitis.

Meningitis is an inflammatory syndrome involving the meninges that classically manifests with headache and nuchal rigidity and is diagnosed by cerebrospinal fluid examination. In contrast, encephalitis refers to inflammation of the brain parenchyma itself and often results in focal neurologic deficits or seizures. In this article, the authors review the differential diagnosis of meningitis and encephalitis, with an emphasis on infectious etiologies. The recommended practical clinical approach focuses on early high-yield diagnostic testing and empiric antimicrobial administration, given the high morbidity associated with these diseases and the time-sensitive nature of treatment initiation. If the initial workup does not yield a diagnosis, further etiology-specific testing based upon risk factors and clinical characteristics should be pursued. Effective treatment is available for many causes of meningitis and encephalitis, and when possible should address both the primary disease process as well as potential complications.