Project description:ObjectiveTo determine which findings on routine clinical EEGs correlate with delirium severity across various presentations and to determine whether EEG findings independently predict important clinical outcomes.MethodsWe prospectively studied a cohort of nonintubated inpatients undergoing EEG for evaluation of altered mental status. Patients were assessed for delirium within 1 hour of EEG with the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) and 3D-CAM severity score. EEGs were interpreted clinically by neurophysiologists, and reports were reviewed to identify features such as theta or delta slowing and triphasic waves. Generalized linear models were used to quantify associations among EEG findings, delirium, and clinical outcomes, including length of stay, Glasgow Outcome Scale scores, and mortality.ResultsWe evaluated 200 patients (median age 60 years, IQR 48.5-72 years); 121 (60.5%) met delirium criteria. The EEG finding most strongly associated with delirium presence was a composite of generalized theta or delta slowing (odds ratio 10.3, 95% confidence interval 5.3-20.1). The prevalence of slowing correlated not only with overall delirium severity (R 2 = 0.907) but also with the severity of each feature assessed by CAM-based delirium algorithms. Slowing was common in delirium even with normal arousal. EEG slowing was associated with longer hospitalizations, worse functional outcomes, and increased mortality, even after adjustment for delirium presence or severity.ConclusionsGeneralized slowing on routine clinical EEG strongly correlates with delirium and may be a valuable biomarker for delirium severity. In addition, generalized EEG slowing should trigger elevated concern for the prognosis of patients with altered mental status.
Project description:Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality of life and placing an immense burden on primary caregivers. Due to a growing number of sepsis survivors, these long-lasting deficits are increasingly relevant. Despite the high incidence and clinical relevance, the pathomechanisms of acute and chronic stages in sepsis-associated encephalopathy are only incompletely understood, and no specific therapeutic options are yet available. Here, we review the emergence of sepsis-associated encephalopathy from initial clinical presentation to long-term cognitive impairment in sepsis survivors and summarize pathomechanisms potentially contributing to the development of sepsis-associated encephalopathy.
Project description:To develop a physiologic grading system for the severity of acute encephalopathy manifesting as delirium or coma, based on EEG, and to investigate its association with clinical outcomes.DesignThis prospective, single-center, observational cohort study was conducted from August 2015 to December 2016 and October 2018 to December 2019.SettingAcademic medical center, all inpatient wards.Patients/subjectsAdult inpatients undergoing a clinical EEG recording; excluded if deaf, severely aphasic, developmentally delayed, non-English speaking (if noncomatose), or if goals of care focused primarily on comfort measures. Four-hundred six subjects were assessed; two were excluded due to technical EEG difficulties.InterventionsNone.Measurements and main resultsA machine learning model, with visually coded EEG features as inputs, was developed to produce scores that correlate with behavioral assessments of delirium severity (Confusion Assessment Method-Severity [CAM-S] Long Form [LF] scores) or coma; evaluated using Spearman R correlation; area under the receiver operating characteristic curve (AUC); and calibration curves. Associations of Visual EEG Confusion Assessment Method Severity (VE-CAM-S) were measured for three outcomes: functional status at discharge (via Glasgow Outcome Score [GOS]), inhospital mortality, and 3-month mortality. Four-hundred four subjects were analyzed (mean [sd] age, 59.8 yr [17.6 yr]; 232 [57%] male; 320 [79%] White; 339 [84%] non-Hispanic); 132 (33%) without delirium or coma, 143 (35%) with delirium, and 129 (32%) with coma. VE-CAM-S scores correlated strongly with CAM-S scores (Spearman correlation 0.67 [0.62-0.73]; p < 0.001) and showed excellent discrimination between levels of delirium (CAM-S LF = 0 vs ≥ 4, AUC 0.85 [0.78-0.92], calibration slope of 1.04 [0.87-1.19] for CAM-S LF ≤ 4 vs ≥ 5). VE-CAM-S scores were strongly associated with important clinical outcomes including inhospital mortality (AUC 0.79 [0.72-0.84]), 3-month mortality (AUC 0.78 [0.71-0.83]), and GOS at discharge (0.76 [0.69-0.82]).ConclusionsVE-CAM-S is a physiologic grading scale for the severity of symptoms in the setting of delirium and coma, based on visually assessed electroencephalography features. VE-CAM-S scores are strongly associated with clinical outcomes.
Project description:PurposeDelirium is an underdiagnosed complication on intensive care units (ICU). We hypothesized that a score-based delirium detection using the Nudesc score identifies more patients compared to a traditional diagnosis of delirium by ICU physicians.MethodsIn this retrospective study, all patients treated on a general medical ICU with 30 beds in a university hospital in 2019 were analyzed. Primary outcome was a documented physician diagnosis of delirium, or a delirium score ≥2 using the Nudesc.ResultsIn 205/943 included patients (21.7%), delirium was diagnosed by ICU physicians compared to 438/943 (46.4%; ratio 2.1) by Nudesc≥2. Both assessments were independent predictors of ICU stay (p<0.01). The physician diagnosis however was no independent predictor of mortality (OR 0.98 (0.57-1.72); p = 0.989), in contrast to the score-based diagnosis (OR 2.31 (1.30-4.10); p = 0.004). Subgroup analysis showed that physicians underdiagnosed delirium in case of hypoactive delirium and delirium in patients with female gender and in patients with an age below 60 years.ConclusionDelirium in patients with hypoactive delirium, female patients and those below 60 years was underdiagnosed by physicians. The score-based delirium diagnosis detected delirium more frequently and correlated with ICU mortality and stay.
Project description:Delirium is a neurocognitive syndrome arising from acute global brain dysfunction, and is prevalent in up to 42% of patients admitted to palliative care inpatient units. The symptoms of delirium and its associated communicative impediment invariably generate high levels of patient and family distress. Furthermore, delirium is associated with significant patient morbidity and increased mortality in many patient populations, especially palliative care where refractory delirium is common in the dying phase. As the clinical diagnosis of delirium is frequently missed by the healthcare team, the case for regular screening is arguably very compelling. Depending on its precipitating factors, a delirium episode is often reversible, especially in the earlier stages of a life-threatening illness. Until recently, antipsychotics have played a pivotal role in delirium management, but this role now requires critical re-evaluation in light of recent research that failed to demonstrate their efficacy in mild- to moderate-severity delirium occurring in palliative care patients. Non-pharmacological strategies for the management of delirium play a fundamental role and should be optimized through the collective efforts of the whole interprofessional team. Refractory agitated delirium in the last days or weeks of life may require the use of pharmacological sedation to ameliorate the distress of patients, which is invariably juxtaposed with increasing distress of family members. Further evaluation of multicomponent strategies for delirium prevention and treatment in the palliative care patient population is urgently required.
Project description:Acute necrotizing encephalopathy after an acute febrile illness, although initially described exclusively in the pediatric age group, has been recently shown to have an adult onset as well. In this study, we describe 10 patients (16 years of age or older) with acute necrotizing encephalopathy. In our study, bilateral thalamic involvement with the trilaminar pattern of diffusion restriction on MR imaging was the predominant finding seen in all of the patients reviewed. Ancillary findings of cerebral white matter, brain stem, and cerebellum involvement with sparing of the basal ganglia were also noted. A poorer outcome was observed in patients with a higher degree of thalamic involvement. The cause of an underlying infection was identified in 4 patients (dengue in 3 and influenza in 1). Overall, a sizeable portion of young adults with acute necrotizing encephalopathy have shown a poorer outcome, with dengue being an important underlying trigger in an endemic region.
Project description:Delirium is associated with increased mortality, morbidity, and length of hospital stay. In the acute stroke setting, delirium identification is challenging due to the complexity of cognitive screening in this patient group. The aim of this study was to explore how members of interprofessional stroke-unit teams identified and responded to a potential delirium in a patient. Online focus groups and interviews utilizing case vignettes were conducted with 15 participants: nurses, occupational therapists, speech and language therapists, and physiotherapists working in acute stroke services. Participants' understandings of delirium varied, most participants did not identify the symptoms of a possible hypoactive delirium, and nearly all participants discussed delirium symptoms in tentative terms. Aspects of interprofessional working were discussed through the expression of distinct roles around delirium identification. Although participants demonstrated an ethos of person-focused care, there are ongoing challenges involved in early identification and management of delirium in stroke survivors.
Project description:Genetic (also known as familial) acute necrotizing encephalopathy (ANE1) is a rare disease presenting with encephalopathy often following preceding viral febrile illness in patients with a genetic predisposition resulting from a missense mutation in the gene encoding RAN Binding Protein 2 (RANBP2). The acute episode is characterized by deterioration in consciousness, often with focal neurologic deficits and seizures. Additionally, symmetric multifocal brain lesions are seen in the bilateral thalami as well as other characteristic regions, involving both gray and white matter. Prognosis is variable, with a high mortality rate and most surviving patients having persistent neurologic deficits. Early treatment with high dose steroids is associated with a more favorable outcome, however the diagnosis is often overlooked resulting in delayed treatment. The RANBP2 mutation associated with ANE1 causes an incompletely penetrant predisposition to encephalopathy in the setting of febrile illness through a mechanism that remains elusive. There are several non-mutually exclusive hypotheses suggesting possible etiologies for this phenotype based on the many functions of RANBP2 within the cell. These include dysfunctions in nucleocytoplasmic trafficking and intracellular metabolic regulation, as well as cytokine storm, and abnormal distribution of mitochondria. This narrative review explores these key concepts of the RANBP2 mutation and its clinical and therapeutic implications in pediatric populations.
Project description:BackgroundNeurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients.MethodsWe conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms.ResultsThe 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2.Conclusions and relevanceDelirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources.Trial registrationNA.
Project description:ObjectiveEncephalopathy is a major neurological complication of severe Coronavirus Disease 2019 (COVID-19), but has not been fully defined yet. Further, it remains unclear whether neurological manifestations are primarily due to neurotropism of the virus, or indirect effects, like cerebral hypoxia.MethodsWe analysed the electroencephalograms (EEGs) of 19 consecutive patients with laboratory-confirmed COVID-19, performed at peak disease severity as part of their clinical management. Disease severity, respiratory failure, immune and metabolic dysfunction, sedation status, and neurological examination on the day of the EEG were noted.ResultsSevere encephalopathy was confirmed in 13 patients, all with severe COVID-19; 10 remained comatose off sedation, and five of them had alpha coma (AC). Disease severity, sedation, immune and metabolic dysfunction were not different between those with AC and those without.ConclusionsSevere COVID-19 encephalopathy is a principal cause of persisting coma after sedation withdrawal. The relatively high incidence of the rare AC pattern may reflect direct SARS-CoV-2 neurotropism with a predilection for the brainstem ascending reticular system.SignificanceSystematic early EEG detection of encephalopathy related to severe COVID-19 is important for the acute care and the management of long-term neurological and cognitive sequelae, and may help our better understanding of its pathophysiology.