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Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed. [ABSTRACT FROM AUTHOR]

Background: Hyperacute hepatic failure (HHF) has a high mortality rate that is most commonly due to severe cerebral edema. However, brain swelling and marked clinical and EEG suppression are potentially reversible, even though the same findings are associated with a very poor neurological outcome in anoxic-ischemic encephalopathy.Methods: We present three cases that illustrate neurological recovery despite severe brain swelling and loss of EEG activity.Results: All patients recovered conscious awareness, including one who transiently lost cranial nerve reflexes.Conclusions: Despite deep coma, markedly suppressed EEG and brain edema, aggressive control of ICP may lead to good recovery in acute hepatic failure. [ABSTRACT FROM AUTHOR]

Background: Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy., Methods: This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged ≥40 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study., Results: A total of 101 participants were randomized. Average enrollment was 10 participants/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (±10.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32-1.93]; P =0.59) favoring the intervention., Conclusions: A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04142125., Competing Interests: Dr Perera reports grants from Bayer AG. Dr Sharma reports grants from Bayer to others; compensation from Bayer for consultant services; and employment by McMaster University. Dr Eikelboom reports compensation from Anthos Pharmaceuticals for consultant services; compensation from Servier Pharmaceuticals LLC for other services; compensation from GlaxoSmithKline for other services; compensation from Janssen Biotech for other services; compensation from Bayer for other services; compensation from Pfizer Canada, Inc for other services; compensation from Bristol-Myers Squibb Canada for other services; compensation from Eli Lilly and Company for consultant services; compensation from Pfizer Canada, Inc for other services; employment by McMaster University; compensation from Daiichi Sankyo Company for other services; compensation from Sanofi Pasteur, Inc for other services; compensation from Merck for other services; compensation from Boehringer Ingelheim for other services; and compensation from AstraZeneca for other services. Dr Ng reports employment by McMaster University. Dr Field reports compensation from Novartis for consultant services; compensation from Bayer for consultant services; service as a Board Member for Destine Health; compensation from AstraZeneca Canada for consultant services; compensation from HLS Therapeutics for consultant services; and compensation from the Canadian Medical Protective Association for expert witness services. Dr Hill reports grants from Boehringer Ingelheim; employment by the University of Calgary; grants from the Canadian Institutes of Health Research; grants from NoNO, Inc; and compensation from Merck for end point review committee services. Dr Shoamanesh reports grants from Bayer; compensation from Bayer for consultant services; compensation from Bayer for data and safety monitoring services; and grants from Bayer. Dr Swartz reports compensation from F. Hoffmann-La Roche for consultant services and stock holdings in FollowMD, Inc. Dr Katsanos reports employment by McMaster University and grants from the Heart and Stroke Foundation of Canada. The other authors report no conflicts.

Concepts of consciousness and its disorders begin with the realization that both reside in the brain. Then came the realization that consciousness had various components, with two principal aspects, wakefulness and awareness. Awareness has multiple interconnected components, ranging from perception to abstract thought. These require selection of certain stimuli and processing as well as judgment and motivation, colored by emotion, before a consciously directed action is produced. The brain processes information and can influence behavior at levels below conscious awareness. Deeper insights into underlying neuronal functions and the complex interactions of various brain regions that support conscious experience have been made possible by scientific and technologic advancements. Our understanding of regional and global brain functions has been influenced by studies of various diseases and disorders, ranging from "brain death" to delirium. We now recognize that we cannot solely rely on behavioral responses to determine the conscious level, as some "unresponsive-wakeful," previously termed "vegetative," patients retain cognitive capacity, revealed by fMRI and electrophysiologic advances. There is still much to learn, especially as to how full awareness and the awareness of awareness arise from the brain and how to best assess and manage patients with various disorders of consciousness., (Copyright © 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

New-onset refractory status epilepticus (NORSE) is a clinical presentation where an individual develops refractory status epilepticus without active epilepsy, or related neurological conditions. A subset of these individuals has a preceding fever and would be diagnosed with febrile infection-related epilepsy syndrome (FIRES). The underlying etiology of this condition varies and includes autoimmune and viral encephalitides. These conditions require multiple specialized health care teams working collaboratively and specific resources for investigation of the underlying etiology and management to provide optimal patient care. In this paper, we provide: (1) recommendations upon early recognition of NORSE and FIRES, (2) guidance on the resources needed to optimally provide care, and (3) guidance on considerations to initiate transfer of patients to a more specialized medical center. Additional recommendations for resource-austere centers without the ability to transfer such patients are also discussed. These recommendations are only for adult patients with NORSE as pediatric patients may require additional special considerations., Competing Interests: The authors declare that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vinette, Young and Khosravani.)

Objective: Little is known about residual cognitive function in the earliest stages of serious brain injury. Functional neuroimaging has yielded valuable diagnostic and prognostic information in chronic disorders of consciousness, such as the vegetative state (also termed unresponsive wakefulness syndrome). The objective of the current study was to determine if functional neuroimaging could be efficacious in the assessment of cognitive function in acute disorders of consciousness, such as coma, where decisions about the withdrawal of life-sustaining therapies are often made., Methods: A hierarchical functional magnetic resonance imaging (fMRI) approach assessed sound perception, speech perception, language comprehension, and covert command following in 17 critically ill patients admitted to the intensive care unit (ICU)., Results: Preserved auditory function was observed in 15 patients (88%), whereas 5 (29%) also had preserved higher-order language comprehension. Notably, one patient could willfully modulate his brain activity when instructed to do so, suggesting a level of covert conscious awareness that was entirely inconsistent with his clinical diagnosis at the time of the scan. Across patients, a positive relationship was also observed between fMRI responsivity and the level of functional recovery, such that patients with the greatest functional recovery had neural responses most similar to those observed in healthy control participants., Interpretation: These results suggest that fMRI may provide important diagnostic and prognostic information beyond standard clinical assessment in acutely unresponsive patients, which may aid discussions surrounding the continuation or removal of life-sustaining therapies during the early post-injury period. ANN NEUROL 2023;93:131-141., (© 2022 American Neurological Association.)

Background: A one-channel electrocardiogram (ECG) channel is recommended during electroencephalogram (EEG) recordings principally to help establish ECG or pulse wave contamination of the ECG EEG. However, the ECG recording, in itself, provides useful clinical information, principally the detection of arrhythmias, especially atrial fibrillation (AF), which indicates heart disease that can predispose to embolic stroke and systemic embolism. We sought to determine the prevalence of AF routine recordings in our EEG laboratory in a general hospital., Methods: We reviewed the consecutive EEG reports for the past 7 years to determine how often AF was detected in various age groups., Results: We found AF in 0-0.2% per decade of life until age 60-69 years, 2.7% for 70-79 years, 5% for 80-89 years, and 8% for 90-99 years., Conclusion: We suggest that the ECG trace should be carefully analyzed for AF, especially in patients over 60 years of age. When detected, it should be brought to the referring doctor's attention.

Anti-Hu-associated neurologic autoimmunity most often occurs in the context of small cell lung cancer and typically presents with peripheral neuropathy, cerebellar ataxia, and/or limbic encephalitis. Extra-limbic encephalitis causing seizures is a rare disease manifestation, with only sparse reports in the literature. Herein we present a patient with seizures in anti-Hu-associated extra-limbic encephalitis, and review the literature for other cases to more fully characterize this entity. Among 27 patients we identified, the median age was 46 years (range: 2-69 years) and 18 of 27 (67%) were female. Focal motor seizures were most common, followed by ictal expressive speech difficulty. Seizure semiologies along with neuroimaging findings most frequently suggested the involvement of the peri-Rolandic cortex, more anterior frontal operculum, and insula, although other cortical regions were rarely affected as well. In contrast to other classical paraneoplastic neurologic syndromes, good response to treatment with attainment of seizure-free survival was often reported, although over one-third still died. A propensity for chronic seizures among children indicated the potential to develop autoimmune-associated epilepsy. The predilection for certain extra-limbic regions, as well as the possibility of good response to treatment, may reflect unique disease mechanisms that would benefit from further study., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Rationale: Prescribed opioids are major contributors to the international public health opioid crisis. Such widespread iatrogenic harms usually result from collective decision failures of healthcare organizations rather than solely of individual organizations or professionals. Findings from a system-wide safety analysis of the iatrogenic opioid crisis that includes roles of pertinent healthcare organizations may help avoid or mitigate similar future iatrogenic consequences. In this retrospective exploratory study, we report such an analysis., Methods: The study population encompassed the entire age spectrum and included those in whom opioids prescribed for chronic pain (unrelated to malignancy) were associated with death or morbidity. Root cause analysis, incorporating recent suggestions for improvement, was used to identify possible contributory factors from the literature. Based on their mandated roles and potential influences to prevent or mitigate the iatrogenic crisis, relevant organizations were grouped and stratified from most to least influential., Results: The analysis identified a chain of multiple interrelated causal factors within and between organizations. The most influential organizations were pharmaceutical, political, and drug regulatory; next: experts and their related societies, and publications. Less influential: accreditation, professional licensing and regulatory, academic and healthcare funding bodies. Collectively, their views and decisions influenced prescribing practices of frontline healthcare professionals and advocacy groups. Financial associations between pharmaceutical and most other organizations/groups were common. Ultimately, patients were adversely affected. There was a complex association with psychosocial variables., Limitations: The analysis suggests associations not causality., Conclusion: The iatrogenic crisis has multiple intricately linked roots. The major catalyst: pervasive pharma-linked financial conflicts of interest (CoIs) involving most other healthcare organizations. These extensive financial CoIs were likely triggers for a cascade of erroneous decisions and actions that adversely affected patients. The actions and decisions of pharma ranged from unethical to illegal. The iatrogenic opioid crisis may exemplify 'institutional corruption of pharmaceuticals'., (© 2021 John Wiley & Sons Ltd.)

Background: We reviewed numerous variables for ischemic stroke patients admitted to a rehabilitation unit to determine those that were statistically associated with discharge destination., Methods: A retrospective chart review of patients with ischemic stroke discharged from the rehabilitation unit between January 1, 2005 and December 31, 2015. Variables were examined for their association with discharge destination (home versus long-term care (LTC)). Univariable relationships with discharge destination were assessed, and a multivariable logistic regression model was built., Results: Univariate predictors of discharge to LTC: advanced age, decreasing admission and discharge functional independence measure (FIM) scores, increasing change in FIM score from admission to discharge, dependency, residence outside of home before the stroke, absence of a caregiver, urinary and bowel incontinence, low Berg balance score at admission and discharge, low Montreal Cognitive Assessment scores, smoking, chronic heart failure, and an inability to transfer. Multivariable logistic regression: five factors remained significant predictors with LTC disposition: advanced age, bowel incontinence, residence outside of the home prior to stroke, right hemisphere site of the stroke, and absence of a caregiver., Conclusions: Several easily measured variables were significantly associated with discharge to LTC versus home following stroke rehabilitation.