Corrigendum: How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis.

[This corrects the article DOI: 10.3389/fneur.2023.1103664.].

How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis.

Introduction: Long-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS), but occult AF is also found in some individuals without a stroke history and in patients with stroke of a known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal vs. incidental. Methods: Through a systematic search, we identified all case-control and cohort studies applying identical long-term monitoring techniques to both patients with CS and KS. We performed a random-effects meta-analysis across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients and across age subgroups. We then applied Bayes' theorem to determine the probability that occult AF is causal or incidental. Results: The systematic search identified three case-control and cohort studies enrolling 560 patients (315 CS, 245 KS). Methods of long-term monitoring were implantable loop recorder in 31.0%, extended external monitoring in 67.9%, and both in 1.2%. Crude cumulative rates of AF detection were CS 47/315 (14.9%) vs. KS 23/246 (9.3%). In the formal meta-analysis, the summary odds ratio for occult AF in CS vs. KS in all patients was 1.80 (95% CI, 1.05-3.07), p = 0.03. With the application of Bayes' theorem, the corresponding probabilities indicated that, when present, occult AF in patients with CS is causal in 38.2% (95% CI, 0-63.6%) of patients. Analyses stratified by age suggested that detected occult AF in patients with CS was causal in 62.3% (95 CI, 0-87.1%) of patients under the age of 65 years and 28.5% (95 CI, 0-63.7%) of patients aged 65 years and older but estimates had limited precision. Conclusion: Current evidence is preliminary, but it indicates that in cryptogenic stroke when occult AF is found, it is causal in about 38.2% of patients. These findings suggest that anticoagulation therapy may be beneficial to prevent recurrent stroke in a substantial proportion of patients with CS found to have occult AF.

Mycotic aneurysm.

Angioinvasive fungal infections of the cerebral vasculature often lead to significant morbidity and mortality. High clinical suspicion and early antifungal therapy could improve outcomes. We describe the fatal case of a patient with a rapidly enlarging cavernous carotid aneurysm due to angioinvasive fungus. This case highlights the challenges in diagnosis and management of this condition.

Incidence and Predictive Factors Associated with Beta-Lactam Neurotoxicity in the Critically Ill: A Retrospective Cohort Study.

BACKGROUND: Beta-lactam neurotoxicity is a relatively uncommon yet clinically significant adverse effect in critically ill patients. This study sought to define the incidence of neurotoxicity, derive a prediction model for beta-lactam neurotoxicity, and then validate the model in an independent cohort of critically ill adults. METHODS: This retrospective cohort study evaluated critically ill patients treated with ≥ 48 h of cefepime, piperacillin/tazobactam, or meropenem. Two separate cohorts were created: a derivation cohort and a validation cohort. Patients were screened for beta-lactam neurotoxicity by using search terms and diagnosis codes, followed by clinical adjudication using a standardized adverse event scoring tool. Multivariable regression models and least absolute shrinkage and selection operator were used to identify surrogates for neurotoxicity and develop a multivariable prediction model. RESULTS: The overall incidence of beta-lactam neurotoxicity was 2.6% (n/N = 34/1323) in the derivation cohort and 2.1% in the validation cohort (n/N = 16/767). The final multivariable neurotoxicity assessment tool included weight, Charlson comorbidity score, age, and estimated creatinine clearance as predictors of neurotoxicity. Incidence of neurotoxicity reached 4% in those with a body mass index more than 30 kg/m2. Use of the candidate variables in the neurotoxicity assessment tool suggested that a score more than 35 would identify a patient at high risk for neurotoxicity with 75% sensitivity and 54% specificity. CONCLUSIONS: In this single center cohort of critically ill patients, beta-lactam neurotoxicity was demonstrated less frequently than previously reported. We identified obesity as a novel risk factor for the development of neurotoxicity. The prediction model needs to be further refined before it can be used in clinical practice as a tool to avoid drug-related harm.

Acute Epstein-Barr virus infection presenting as Guillain-Barre syndrome.

An 18-year-old man presented with 5-days of a lower extremity rash, sore throat, rapidly progressive bilateral facial numbness and paresthesias in his distal extremities. His neurological examination acutely deteriorated to include moderate bilateral facial weakness in a lower motor neuron pattern, mild flaccid dysarthria, mild bilateral interossei weakness, and diffuse hyporeflexia. In addition to neurological examination, EMG results of acute demyelinating polyradiculoneuropathy were suggestive of Guillain-Barre Syndrome (GBS). Infectious laboratory testing demonstrated acute infection of Epstein-Barr Virus (EBV) with relatively low EBV DNA quantitative values. The patient subsequently developed fever and cervical lymphadenopathy during his hospital course. Contrasting typical GBS, which presents weeks after an acute infection, the patient's presenting symptom of EBV infection was GBS. GBS as a presenting symptom of EBV has not previously been described. This case may represent a unique mechanism for the pathogenesis of GBS in acute infections as opposed to the traditional post-infectious antibody-mediated process.

Lacosamide Pharmacokinetics in a Critically Ill Patient During Continuous Renal Replacement Therapy.

The objective of this study is to describe the pharmacokinetics of lacosamide in a critically ill adult during continuous venovenous hemofiltration (CVVH). A 78-year-old male developed sepsis and acute kidney injury following cardiac surgery. He was initially treated with intermittent hemodialysis but developed nonconvulsive status epilepticus at the end of the first session and was subsequently initiated on CVVH. In addition to lorazepam boluses, levetiracetam, and midazolam infusion, he was loaded with lacosamide 400 mg intravenously and started on 200 mg intravenously twice daily as maintenance therapy. Noncompartmental modeling of lacosamide pharmacokinetics revealed significant extracorporeal removal, a volume of distribution of 0.69 L/kg, elimination half-life of 13.6 hours, and peak and trough concentrations of 7.4 and 3.7 mg/L, respectively (goal trough, 5-10 mg/L). We found significant extracorporeal removal of serum lacosamide during CVVH, which was higher than previously reported. This led to subtherapeutic concentrations and decreased overall antiepileptic drug exposure. The relationship between serum lacosamide concentrations and clinical efficacy is not well understood; thus, therapeutic drug monitoring is not routinely recommended. Yet, we demonstrated that measuring serum lacosamide concentrations in the critically ill population during continuous renal replacement therapy may be useful to individualize dosing programs. Further pharmacokinetic studies of lacosamide may be necessary to generate widespread dosing recommendations.

Variable Significance of Brain MRI Findings in Infective Endocarditis and Its Effect on Surgical Decisions.

OBJECTIVE: To determine how brain magnetic resonance imaging (MRI) findings impact clinical outcomes in patients with infective endocarditis (IE) and to propose a management algorithm for patients with neurologic symptoms who are candidates for valve surgery (VS). PATIENTS AND METHODS: Data from our center were retrospectively reviewed for patients hospitalized with IE between January 1, 2007, and December 31, 2014. Outcomes were postoperative intracerebral hemorrhage (ICH), 6-month mortality, and functional outcome at last follow-up as described by the modified Rankin Scale (mRS) score. Good outcome was defined as an mRS score of 2 or less. RESULTS: A total of 361 patients with IE were identified, including 127 patients (35%) who had MRI. One hundred twenty-six of 361 patients (35%) had neurologic symptoms, which prompted MRI in 79 of 127 patients (62%); 74 of 79 (94%) had acute or subacute MRI abnormalities. One patient with subarachnoid and multifocal ICH on MRI developed postoperative ICH. Patients with VS despite MRI abnormalities had lower 6-month mortality (odds ratio [OR], 0.17; 95% CI, 0.06-0.48; P<.001) and better functional outcome (OR, 4.43; 95% CI, 1.51-13.00; P=.005). Irrespective of VS, lobar or posterior fossa ICH on MRI was associated with 6-month mortality (OR, 3.58; 95% CI, 1.22-10.50; P=.02) and territorial ischemic stroke was inversely associated with good mRS (OR, 0.29; 95% CI, 0.13-0.66; P=.002). In neurologically asymptomatic patients who had VS, MRI findings did not impact 6-month mortality or functional outcomes. CONCLUSION: Magnetic resonance imaging detects a large number of abnormalities in patients with IE. Preoperative lobar hematoma and large territorial stroke determine outcome irrespective of VS. When indicated, VS increases the odds of a good outcome despite MRI abnormalities.

Application of the FOUR Score in Intracerebral Hemorrhage Risk Analysis.

BACKGROUND: The Full Outline of Unresponsiveness (FOUR) Score is a validated scale describing the essentials of a coma examination, including motor response, eye opening and eye movements, brainstem reflexes, and respiratory pattern. We incorporated the FOUR Score into the existing ICH Score and evaluated its accuracy of risk assessment in spontaneous intracerebral hemorrhage (ICH). MATERIALS AND METHODS: Consecutive patients admitted to our institution from 2009 to 2012 with spontaneous ICH were reviewed. The ICH Score was calculated using patient age, hemorrhage location, hemorrhage volume, evidence of intraventricular extension, and Glasgow Coma Scale (GCS). The FOUR Score was then incorporated into the ICH Score as a substitute for the GCS (ICH ScoreFS). The ability of the 2 scores to predict mortality at 1 month was then compared. RESULTS: In total, 274 patients met the inclusion criteria. The median age was 73 years (interquartile range 60-82) and 138 (50.4%) were male. Overall mortality at 1 month was 28.8% (n = 79). The area under the receiver operating characteristic curve was .91 for the ICH Score and .89 for the ICH ScoreFS. For ICH Scores of 1, 2, 3, 4, and 5, 1-month mortality was 4.2%, 29.9%, 62.5%, 95.0%, and 100%. In the ICH ScoreFS model, mortality was 10.7%, 26.5%, 64.5%, 88.9%, and 100% for scores of 1, 2, 3, 4, and 5, respectively. CONCLUSIONS: The ICH Score and the ICH ScoreFS predict 1-month mortality with comparable accuracy. As the FOUR Score provides additional clinical information regarding patient status, it may be a reasonable substitute for the GCS into the ICH Score.

Ventriculostomy and Risk of Upward Herniation in Patients with Obstructive Hydrocephalus from Posterior Fossa Mass Lesions.

BACKGROUND: Patients with posterior fossa lesions causing obstructive hydrocephalus present a unique clinical challenge, as relief of hydrocephalus can improve symptoms, but the perceived risk of upward herniation must also be weighed against the risk of worsening or continued hydrocephalus and its consequences. The aim of our study was to evaluate for clinically relevant upward herniation following external ventricular drainage (EVD) in patients with obstructive hydrocephalus due to posterior fossa lesions. METHODS: We performed a retrospective review of patients undergoing urgent/emergent EVD placement at our institution between 2007 and 2014, evaluating the radiographic and clinical changes following treatment of obstructive hydrocephalus. RESULTS: Even prior to EVD placement, radiographic upward herniation was present in 22 of 25 (88%) patients. The average Glasgow Coma Scale of patients before and after EVD placement was 10 and 11, respectively. Radiographic worsening of upward herniation occurred in two patients, and upward herniation in general persisted in 21 patients. Clinical worsening occurred in two patients (8%), though in all others the clinical examination remained stable (44%) or improved (48%) following EVD placement. Of the patients who had a worsening clinical exam, other variables likely also contributed to their decline, and cerebrospinal fluid diversion was likely not the main factor that prompted the clinical change. CONCLUSIONS: Radiographic presence of upward herniation was often present prior to EVD placement. Clinically relevant upward herniation was rare, with only two patients worsening after the procedure, in the presence of other clinical confounders that likely contributed as well.

Medulla Oblongata Hemorrhage and Reverse Takotsubo Cardiomyopathy.

BACKGROUND: Acute brain injury with strong surges of adrenergic outflow has resulted in takotsubo cardiomyopathy, but there are surprisingly few reports of takotsubo cardiomyopathy after intracranial hemorrhage, and none have been described from hemorrhage within the brainstem. RESULTS: We describe a patient with reverse and reversible cardiomyopathy following a hemorrhage in the lateral medulla oblongata. While it is limited in size, the location of the hemorrhage caused acute systolic failure with left ventricular ejection fraction of 27% and vasopressor requirement for cardiogenic shock and pulmonary edema. There was full recovery after 7 days. METHODS: Detailed case report. CONCLUSION: Hemorrhage into medulla oblongata pressor centers may result in acute, reversible, stress-induced cardiomyopathy, affirming the adrenergic origin of this condition.

Variability of stroke patients meeting endovascular stroke trial criteria in a non-clinical trial setting.

BACKGROUND: Five randomized trials proving the efficacy and safety of mechanical embolectomy for ischemic stroke within 8hours used differing radiological methods to select patients. We aimed to evaluate the proportion of patients in clinical practice that would meet radiological criteria for inclusion in these trials. METHODS: Retrospective study of ischemic stroke patients at a large academic medical center who were considered for endovascular stroke therapy based on confirmed intracranial large vessel occlusion from April 2010-November 2014. All patients underwent computed tomography (CT) perfusion and CT angiogram. RESULTS: Of 119 patients, median age was 69 years (IQR 57-79) and median NIHSS 18 (IQR 14-21). Most patients had ASPECTS≥6 (n=105, 88.2%). All 119 patients met radiological criteria for MR CLEAN while 105 (88.2%) met criteria for SWIFT-PRIME, 96 (80.7%) for REVASCAT, 80/116 (69.0%) for EXTEND-IA, and 74 (62.2%) for ESCAPE. About half (n=58,48.7%) were treated with IV rtPA and 66 (56%) underwent endovascular therapy. Any intracranial hemorrhage was more common in patients undergoing endovascular therapy than in those who were not (36% vs. 17%, P=0.034). The frequency of symptomatic intracranial hemorrhage (ICH) did not significantly differ between these groups (6% vs. 4%, P=0.691). CONCLUSIONS: The proportion of patients with acute stroke and large vessel occlusion presenting within 8 hours that would meet radiological criteria for endovascular stroke trials varies considerably (62-100%) in a cohort outside of clinical trials from an academic comprehensive stroke center. Thus, the radiological criteria used for candidate selection in daily practice will greatly influence the proportion of patients treated with endovascular therapy.

Anoxic-Ischemic Brain Injury.

Improvements in cardiopulmonary resuscitation and intensive care medicine have led to declining mortality rates for patients with out-of-hospital cardiac arrest, but overall it is still a minority that achieves good outcomes. Estimating neurologic prognosis for patients that remain comatose after resuscitation remains a challenge and the need for accurate and early prognostic predictors is crucial. A thoughtful approach is required and should take into account information acquired from multiple tests in association with neurologic examination. No decision should be made based on a single predictor. In addition to clinical examination, somatosensory evoked potentials, electroencephalogram, serum biomarkers, and neuroimaging provide complimentary information to inform prognosis.

Utility of Brain Magnetic Resonance Imaging in the Surgical Management of Infective Endocarditis.

BACKGROUND: Brain magnetic resonance imaging (MRI) is frequently obtained in patients with infective endocarditis, yet its utility in predicting outcomes for valve replacement surgery in patients is unknown. The objective of this study was to determine how brain MRI findings impact clinical management and outcomes. METHODS: Demographic and clinical data from electronic medical records at Mayo Clinic were retrospectively reviewed for patients hospitalized with definite or possible infective endocarditis according to the modified Duke criteria between January 1, 2007 and December 31, 2014. There were 364 patients included in the study. RESULTS: Cardiac valve replacement surgery was performed in 195 of 364 (53.6%) patients, and 95 (48.7%) of the surgical patients underwent preoperative MRI, which was associated with preoperative neurologic symptoms in 56 of 95 (58.9%) patients (odds ratio = 12.92; 95% confidence interval, 5.98-27.93; P <.001). Postoperative neurologic complications occurred in 24 of 195 (12.3%) patients, including new ischemic stroke in 4 of 195 (2.1%) and new intracerebral hemorrhage in 3 of 195 (1.5%). No patients with microhemorrhages developed postoperative hemorrhage. No significant differences existed in rates of postoperative complications between patients with and those without preoperative MRI. There were no substantial associations between preoperative MRI findings and postoperative neurologic complications, functional outcomes as described by the modified Rankin Scale score, or 6-month mortality. CONCLUSIONS: In patients undergoing valve replacement surgery, preoperative MRI findings were not associated with differences in postoperative outcomes, irrespective of finding or timing of valve replacement surgery.

Extensive Mobile Thrombus of the Internal Carotid Discovered After Intravenous Thrombolysis: What Do I Do Now?

This case report describes a rare presentation of ischemic stroke secondary to an extensive internal carotid artery thrombus, subsequent therapeutic dilemma, and clinical management. A 58-year-old man was administered intravenous (IV) thrombolysis for right middle cerebral artery territory ischemic stroke symptoms. A computed tomography angiogram of the head and neck following thrombolysis showed a longitudinally extensive internal carotid artery thrombus originating at the region of high-grade calcific stenosis. Mechanical embolectomy was deferred because of risk of clot dislodgement and mild neurological symptoms. Recumbency and hemodynamic augmentation were used acutely to support cerebral perfusion. Anticoagulation was started 24 hours after thrombolysis. Carotid endarterectomy was completed successfully within 1 week of presentation. Clinical outcome was satisfactory with discharge modified Rankin Scale score 0. A longitudinally extensive carotid artery thrombus poses a risk of dislodgement and hemispheric stroke. Optimal management in these cases is not known with certainty. In our case, IV thrombolysis, hemodynamic augmentation, delayed anticoagulation, and carotid endarterectomy resulted in a favorable clinical outcome.

Dual-Energy CT to Diagnose Pseudoedema in Contrast-Induced Encephalopathy Following Cerebral Angiography.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a syndrome that may be clinically unrecognized and misdiagnosed as cerebral edema. METHODS: Case report and review. RESULTS: A 72-year-old woman was admitted for elective endovascular embolization of a 10-mm left anterior communicating artery aneurysm. One hour post-procedure, she acutely developed global aphasia. Emergent head computed tomography (CT) and computed tomography-angiography (CTA) showed high attenuation of the left hemispheric subarachnoid spaces interpreted as hemispheric edema; emergent magnetic resonance imaging revealed left hemispheric punctate infarcts. At 12 h, she developed right hemiparesis and encephalopathy. Repeat CTA and CT perfusion revealed decreased left hemisphere cerebral blood flow and diminutive caliber of distal left middle cerebral artery territory vasculature. Repeated angiography with intra-arterial verapamil and systemic blood pressure augmentation were performed for presumed vasospasm. At 20 h, head CT was concerning for worsening left hemispheric edema, but dual-energy, iodine-subtracting sequences revealed significant contrast extravasation contributing to the appearance of sulcal effacement but without actual edema. Out of concern for blood-brain barrier breakdown from CIE, pressor augmentation was discontinued and the patient gradually improved to full neurological recovery within 72 h of symptom onset. CONCLUSIONS: Our case is the first known to report the use of dual-energy, iodine-subtracting CT as a diagnostic tool in differentiating between cerebral edema and pseudoedema in CIE.

Lumbar drainage and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review.

INTRODUCTION: Lumbar drainage for cerebrospinal fluid (CSF) diversion in aneurysmal subarachnoid hemorrhage (aSAH) has been reported to be beneficial in small series. There is no consensus regarding the optimal candidates for lumbar drainage, timing of drain placement, or amount and duration of CSF drainage. EVIDENCE ACQUISITION: We performed a comprehensive review of the English literature reporting series of patients with aSAH undergoing CSF diversion with lumbar drains. Favorable clinical outcome was defined as modified Rankin Scale of 0-2 or Glasgow Outcome Scale as 4-5. EVIDENCE SYNTHESIS: A total of 8 studies reporting on 841 patients were included. Of these, 446 patients were treated with lumbar drains. Two studies were prospective and five studies had comparison groups. Most patients undergoing lumbar drainage were in good clinical grade on presentation (394/446, 88%) and the majority had substantial clot burden on head CT. Among the five studies with a comparison group, lumbar drainage was associated with lower rates of symptomatic vasospasm or delayed cerebral ischemia (20% vs. 45%, P<0.001) and higher rates of favorable outcome (79.4% vs. 60.4% P<0.001). The complication rate was 3.5%. CONCLUSIONS: Lumbar drainage in aSAH appears to be safe and associated with reduced rates of symptomatic vasospasm and improved clinical outcomes in patients in good clinical grade with thick clot burden, but the quality of most available studies is weak. The optimal duration and rate of CSF diversion remains uncertain.

Post-ischemic Myoclonic Status Following Cardiac Arrest in Young Drug Users.

BACKGROUND: Myoclonic status may be observed following cardiac arrest and has previously been identified as a poor prognostic indicator in regard to return of neurologic function. We describe a unique situation in post-cardiac arrest patients with myoclonic status and hypothesize possible predictors of a good neurologic outcome. METHODS: Case series. RESULTS: We illustrate two cases of cardiac arrest due to a respiratory cause in young patients with evidence of illicit drug use at the time of hospital admission that suffered post-ischemic myoclonic status. These patients subsequently recovered with good neurologic outcomes. CONCLUSIONS: On rare occasions, myoclonic status does not imply a poor functional outcome following cardiac arrest. Other clinical and demographic characteristics including young age, presence of illicit substances, and primary respiratory causes of arrest may contribute to a severe clinical presentation, with a subsequent good neurologic outcome in a small subset of patients.

Routine Troponin Measurements Are Unnecessary to Exclude Asymptomatic Coronary Events in Acute Ischemic Stroke Patients.

BACKGROUND: Obtaining serum troponin levels in every patient with acute stroke is recommended in recent stroke guidelines, but there is no evidence that these contribute positively to clinical care. We sought to determine the clinical significance of measuring troponin levels in acute ischemic stroke patients. METHODS: We reviewed 398 consecutive patients with acute ischemic stroke at a large academic institution from 2010 to 2012. Troponin levels were measured as a result of protocol in place during part of the study period. The mean age was 70 years (standard deviation ±16 years) and 197 (49.5%) were men. RESULTS: Chronic kidney disease was present in 78 (19.6%), coronary artery disease in 107 (26.9%), and atrial fibrillation in 107 (26.9%). Serum troponin T was measured in 246 of 398 patients (61.8%). Troponin was elevated (>.01 ng/mL) at any point in 38 of 246 patients (15.5%) and was elevated in 28 patients at all 3 measurements (11.3% of those with troponin measured). Only 4 of 246 patients (1.6%) had a significant uptrend. Two were iatrogenic in the setting of hemodynamic augmentation using vasopressors to maintain cerebral perfusion. One case was attributed to stroke and chronic kidney disease and another case to heart failure from inflammatory fibrocalcific mitral valvular heart disease. CONCLUSIONS: Serum troponin elevation in patients with ischemic stroke is not usually caused by clinically significant acute myocardial ischemia unless iatrogenic in the setting of vasopressor administration. Serum troponin levels should be measured judicially, based on clinical context, rather than routinely in all stroke patients.