James E. Siegler

Predictors of Finding Occult Atrial Fibrillation After Cryptogenic Stroke

Background and Purpose— Occult paroxysmal atrial fibrillation (AF) is found in a substantial minority of patients with cryptogenic stroke. Identifying reliable predictors of paroxysmal AF after cryptogenic stroke would allow clinicians to more effectively use outpatient cardiac monitoring and ultimately reduce secondary stroke burden. Methods— We analyzed a retrospective cohort of consecutive patients who underwent 28-day mobile cardiac outpatient telemetry after cryptogenic stroke or transient ischemic stroke. Univariate and multivariable analyses were performed to identify clinical, echocardiographic, and radiographic features associated with the detection of paroxysmal AF. Results— Of 227 patients with cryptogenic stroke (179) or transient ischemic stroke (48), 14% (95% confidence interval, 9%–18%) had AF detected on mobile cardiac outpatient telemetry, 58% of which was ≥30 seconds in duration. Age >60 years (odds ratio, 3.7; 95% confidence interval, 1.3–11) and prior cortical or cerebellar infarction seen on neuroimaging (odds ratio, 3.0; 95% confidence interval, 1.2–7.6) were independent predictors of AF. AF was detected in 33% of patients with both factors, but only 4% of patients with neither. No other clinical features (including demographics, CHA2DS2-VASc [combined stroke risk score: congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack, vascular disease, sex] score, or stroke symptoms), echocardiographic findings (including left atrial size or ejection fraction), or radiographic characteristics of the acute infarction (including location, topology, or number) were associated with AF detection. Conclusions— Mobile cardiac outpatient telemetry detects AF in a substantial proportion of cryptogenic stroke patients. Age >60 years and radiographic evidence of prior cortical or cerebellar infarction are robust indicators of occult AF. Patients with neither had a low prevalence of AF.

Global Survey of the Frequency of Atrial Fibrillation-Associated Stroke: Embolic Stroke of Undetermined Source Global Registry.

Background and Purpose— Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Methods— Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Results— Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3–5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). Conclusions— This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.

A Simple Prediction Score for Developing a Hospital-Acquired Infection after Acute Ischemic Stroke

BACKGROUNDnHospital-acquired infections (HAIs) are a major cause of morbidity and mortality in acute ischemic stroke patients. Although prior scoring systems have been developed to predict pneumonia in ischemic stroke patients, these scores were not designed to predict other infections. We sought to develop a simple scoring system for any HAI.nnnMETHODSnPatients admitted to our stroke center (July 2008-June 2012) were retrospectively assessed. Patients were excluded if they had an in-hospital stroke, unknown time from symptom onset, or delay from symptom onset to hospital arrival greater than 48 hours. Infections were diagnosed via clinical, laboratory, and imaging modalities using standard definitions. A scoring system was created to predict infections based on baseline patient characteristics.nnnRESULTSnOf 568 patients, 84 (14.8%) developed an infection during their stays. Patients who developed infection were older (73 versus 64, P < .0001), more frequently diabetic (43.9% versus 29.1%, P = .0077), and had more severe strokes on admission (National Institutes of Health Stroke Scale [NIHSS] score 12 versus 5, P < .0001). Ranging from 0 to 7, the overall infection score consists of age 70 years or more (1 point), history of diabetes (1 point), and NIHSS score (0-4 conferred 0 points, 5-15 conferred 3 points, >15 conferred 5 points). Patients with an infection score of 4 or more were at 5 times greater odds of developing an infection (odds ratio, 5.67; 95% confidence interval, 3.28-9.81; P < .0001).nnnCONCLUSIONnIn our sample, clinical, laboratory, and imaging information available at admission identified patients at risk for infections during their acute hospitalizations. If validated in other populations, this score could assist providers in predicting infections after ischemic stroke.

Elevated Red Cell Distribution Width is Associated with Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage.

BackgroundElevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH).MethodsIn this retrospective single-center cohort of aSAH patients (October 2009–September 2014), elevated RDW was defined as a mean RDW >14.5xa0% during the first 14xa0days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death.ResultsOf 179 patients, 27xa0% had a high Hunt–Hess grade (IV–V), and 76xa0% were women. Twenty-four patients (13.4xa0%) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95xa0% CI, 1.07–6.11], pxa0=xa00.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7xa0%, pxa0=xa00.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95xa0% CI, 1.30–7.32], pxa0=xa00.011), independent of known confounders including but not limited to age, sex, race, high Hunt–Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRSxa0>xa04) at discharge (OR 2.59 [95xa0% CI, 1.04–629], pxa0=xa00.040).ConclusionsRDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

Diagnoses and other predictors of patient absenteeism in an outpatient neurology clinic

Background We sought to determine the neurologic diagnosis or diagnostic categories that are associated with a higher probability of honoring a scheduled follow-up visit in the outpatient clinic. Methods We conducted a retrospective analysis of patients evaluated over a 3-year period (July 2014–June 2017) at a single neurology clinic in an urban location. Adult patients who honored an initial scheduled outpatient appointment were included. Only diagnoses with a ≥0.5% prevalence at our center were analyzed. Mixed-effects logistic regression was used to determine association of independent variables and honored follow-up visits. Results Of 61,232 scheduled outpatient subsequent encounters for 20,729 unique patients, the overall absenteeism rate was 12.5% (95% confidence interval [CI] 12.2%–12.8%). Independent risk factors associated with absenteeism included younger age, black or Latino race/ethnicity, Medicaid/Medicare payor status, and longer delay from appointment scheduling to appointment date. In mixed-effects logistic regression, diagnoses associated with the lowest odds of showing were medication overuse headache (show rate 79.2%, odds ratio [OR] for honoring appointment 0.67, 95% CI 0.48–0.93) and depression (rate 85.9%, OR 0.82, 95% CI 0.70–0.97), whereas the diagnoses associated with the greatest odds of showing included Charcot-Marie-Tooth disease (rate 96.3%, OR 2.54, 95% CI 1.44–4.49) and aphasia (rate 95.9%, OR 2.34, 95% CI 1.28–4.30). Conclusions Certain chronic neurologic diseases, such as medication overuse headache and depression, were associated with a significantly lower odds of honoring scheduled follow-up conditions. As these conditions influence quality of life and productivity, patients with these illnesses may benefit from selective targeting to encourage adherence with scheduled follow-up appointments.

Combination of Intra-Hematomal Hypodensity on CT and BRAIN Scoring Improves Prediction of Hemorrhage Expansion in ICH

BackgroundHematoma expansion (HE) occurs in 1/3 of ICH patients and is associated with poor outcome. Intra-hematomal hypodensity (IHH) on CT has been reported to predict HE, as has the “BRAIN” score. We sought to assess the predictive value of these markers alone and in combination.MethodsWe performed a retrospective single-center study of ICH patients with CTxa0<xa06xa0h from onset. Two blinded neurologists assessed IHH on initial CT. Two HE definitions were examined:xa0>xa06xa0ml andxa0>xa06xa0ml orxa0>xa033%. Multivariable logistic regression was used to determine the relationship between IHH and HE. Predictive value of the BRAIN score alone and integrated with IHH was assessed.ResultsIn 122 included patients, median ICH volume was 13xa0ml, median time to CT 2.0xa0h; HExa0>xa06xa0ml occurred in 31% andxa0>xa06xa0ml/>xa033% in 43% of subjects. IHH were identified in 61% of patients with moderate inter-rater agreement (κxa0=xa00.59). In multivariable analysis, IHH was associated with HE usingxa0>xa06xa0ml definition (OR 8.3, 95% CI, 2.6–32.8, Pxa0<xa00.001) but not using thexa0>xa06xa0ml/>xa033% definition (OR 1.9, 95% CI 0.84–4.3, Pxa0=xa00.12). Rate of HE (>xa06xa0ml) increased across increasing BRAIN score quartiles (Q1:11%, Q2:23%, Q3:43%, Q4:57%, P for trendxa0<xa00.001). Rate of HExa0>xa06xa0ml in patients with BRAIN scorexa0≥xa010 and IHH was 55%, with either alone was 33%, and with neither was 3%.ConclusionsCombining IHH on non-contrast CT and a simple clinical BRAIN score is a potentially powerful way to predict those patients at very high and very low risk of HE.

Clinical Reasoning: A young woman with progressive headache and pancytopenia

A 33-year-old woman was admitted to our hospital for treatment of pancytopenia and rash. Her history was notable for systemic lupus erythematosus as well as antiphospholipid antibody syndrome (APS) manifested by prior deep vein thrombosis, pulmonary embolism, and elevated anticardiolipin antibody (95 G phospholipids), β2 glycoprotein immunoglobulin G (IgG) (81 units/mL), and dilute Russell viper venom time (ratio 1.8). She was treated with enoxaparin 1 mg/kg twice daily for her APS. She also had a history of mild bilateral diffuse throbbing headaches occurring every couple of months beginning in her early 20s. Two weeks prior to admission, while vacationing in the Southeastern United States (without exposure to a forest), she developed chills, fatigue, and throbbing headache radiating to the right side of her face, accompanied by a whooshing sound in her right ear. Several days after headache onset, she presented to an outside hospital, where she reportedly had a normal head CT scan and brain MRI scan, but was noted to be pancytopenic (leukocyte count 0.5 × 103/μL, hemoglobin 7.7 mg/dL, and platelets 9 × 103/μL). She underwent a bone marrow biopsy, the results of which were unremarkable. She was discharged with a prednisone taper for suspected lupus flare. Her headache resolved but 2 days later she developed a new erythematous maculopapular rash involving the palms and soles for which she presented to our emergency room. Her complete blood count on admission was again notable for pancytopenia, with a leukocyte count 0.6 × 103/μL (absolute neutrophil count 900/μL), hemoglobin 8.0 mg/dL, and platelets 13 × 103/μL. Her enoxaparin was held given severe thrombocytopenia. The day after her admission, she developed a progressive return of similar quality right-sided headache again accompanied by a whooshing sound. Her headache was made worse by crying, coughing, and physical exertion. She denied any neurologic deficits and her vital signs were normal.

Late onset progressive multifocal leukoencephalopathy in Hodgkin lymphoma

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from infection of oligodendrocytes in the central nervous system with John Cunningham virus. Although PML is commonly diagnosed in immunocompromised patients with human immunodeficiency virus, it can also arise in other immunodeficient states. In this report, we present an unusual case of PML occurring 40years after chemoradiation therapy for Hodgkin lymphoma in a patient with normal total lymphocyte counts on annual surveillance. Although current guidelines recommend annual complete blood counts for patients in remission, this testing may be insufficient to monitor patients with chronic CD4+ lymphopenia.

The Utility of Quantifiable Neurologic Assessments After Stroke In response to Marsh et al, “The NIH Stroke Scale Has Limited Utility in Accurate Daily Monitoring of Neurologic Status”

In the most recent edition of The Neurohospitalist, Marsh and colleagues reported a significant limitation of serial National Institutes of Health Stroke Scale (NIHSS) assessments in patients with acute ischemic stroke.1 The investigators rightfully concluded that an improvement in 4 points on the NIHSS was less sensitive for detecting neurologic recovery when compared to a comprehensive neurologic examination. Recognition of this weakness is pertinent to all clinicians who rely on the NIHSS to identify neurologic recovery (or worsening), especially when using a prethresholded NIHSS improvement in the definition of recovery. n nThe NIHSS is certainly not a replacement for a full neurologic examination. This tool, however, has traditionally been utilized to quantitate neurologic change in patients with stroke and serves as a useful adjunct in clinical decision-making and for research purposes. In some of the earliest clinical trials using serial NIHSS assessments, a clinically significant change has been prespecified at the same 4-point minimum as in this study.2 This is reasonable given the (1) imperfect interrater reliability and (2) fluctuations in neurologic symptoms depending on patient alertness and time of day, which may render a 2-point threshold less specific. However, in my experience, a 2-point threshold may be more sensitive and maintain a high specificity when compared to these historic 4-point cutoffs.3 As the authors demonstrate,1 a 2-point improvement actually confers nearly identical prognostic information regarding improvement when compared to the comprehensive neurologic assessment. It may even overestimate the degree of improvement. Specifically, at 24 hours post-tissue plasminogen activator, 78% of patients improved by ≥2 points compared to 71% who improved according to non-NIHSS neurologic assessment. At discharge, this rose to 83% and 71%, respectively, and at ∼1-month follow-up, 100% and 95%, respectively. Therefore, a 2-point threshold may perhaps be superior for quantitating improvement in this population when compared to the 4-point cutoff. n nThat being said, should the primary outcome of investigations such as these be improvement? The authors conclude that serial NIHSS assessments are inadequate for capturing changes in functional outcome when in fact their findings indicate inadequately captured improvement. The delivery of positive prognostic information to patients should certainly be pursued and explored with research efforts, but (as the authors affirm) serial NIHSS assessments may be most relevant when “considering functional decline.”1 In my experience3 and others,4 serial NIHSS assessments can successfully capture deterioration. Confirmatory research is called upon to determine whether prethresholded NIHSS changes can be implemented clinically to determine when it is appropriate to intervene and where it may be effective in identifying reversible causes of deterioration. n nThe NIHSS is not an ideal tool for detecting neurologic change after stroke. But a quantitative assessment should be implemented as an adjunct to the physical examination in order to monitor for progression. For the time being, I find it reasonable to perform serial NIHSS assessments in order to detect neurologic deterioration—especially when a lower threshold (eg, 2- vs 4-point worsening) is used to detect a clinically meaningful decline.5

Normonatremic osmotic demyelination in the setting of acquired immune deficiency syndrome and malnutrition: case report and literature review

In this report, we present the case of a 43-year-old woman with AIDS, disseminated aspergillosis, and malnutrition who developed osmotic demyelination syndrome. AIDS-related osmotic demyelination has only been documented in a handful of cases to date, and it appears independent of the classic mechanism of rapid correction of hyponatremia. In this manuscript, we review the six prior cases of osmotic demyelination in AIDS patients and compare their circumstances to that of our own patient. It appears that complications of malnutrition, possibly related to depletion of organic osmolytes in the central nervous system, may place AIDS patients at greater risk of osmotic demyelination. These, and other proposed mechanisms, deserve further inquiry.