Bryan Young

An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring An investigation of variables associated with mortality

Of 49 patients with nonconvulsive seizures studied with continuous EEG monitoring, the overall mortality was 33% (16/49).Of the 23 patients with nonconvulsive status epilepticus (NCSE), 13 died (mortality 57%). Individual variables significantly associated with mortality were age, presence of NCSE, seizure duration, hospital and NICU length of stay, and delay to diagnosis and etiology (acute illness versus remote symptomatic). With multivariate logistic regression, only seizure duration (p = 0.0057, OR = 1.131/hour) and delay to diagnosis (p = 0.0351, OR = 1.039/hour) were associated with increased mortality. Acute symptomatic cases could not be adequately classified as either absence, simple, or complex partial status epilepticus when the impairment of consciousness arose from the initial illness. Current classifications of status epilepticus are inadequate for such cases. NEUROLOGY 1996;47: 83-89

The ACNS subcommittee on research terminology for continuous EEG monitoring: proposed standardized terminology for rhythmic and periodic EEG patterns encountered in critically ill patients.

Continuous EEG monitoring is becoming a commonly usedtool in the assessment of brain function in critically illpatients. However, there is no uniformly accepted nomencla-ture for the EEG patterns frequently encountered in thesepatients, such as periodic discharges, fluctuating rhythmicpatterns, and combinations thereof. Similarly, there is noconsensus regarding which patterns are associated with on-going neuronal injury, which needs to be treated, or howaggressively to treat them. The first step in addressing theseissues is to standardize terminology to allow multicenterresearch projects and to facilitate communication. To thisend, we gathered a group of electroencephalographers withparticular expertise or interest in this area to develop stan-dardized terminology to be used primarily in the researchsetting. One of the main goals was to eliminate terms withclinical connotations, intended or not, such as “triphasicwaves,” a term that implies a metabolic encephalopathy withno relationship to seizures. We also decided to avoid the useof “ictal,” “interictal,” and “epileptiform” for the equivocalpatterns that are the primary focus of this report.A standardized method of quantifying interictal dis-charges is also included for the same reasons, with no attemptto alter the existing definition of epileptiform discharges(sharpwavesandspikes Noachtaretal.,1999 .Similarly,weare not necessarily suggesting abandonment of prior termssuch as periodic lateralized epileptiform discharges (PLEDs)and triphasic waves for clinical use.This is a proposal subject to future modifications basedon use and feedback from others.

Electroencephalogram for prognosis after cardiac arrest

BACKGROUND In assessing neurologic prognosis after cardiac arrest (CA), electroencephalogram (EEG) reactivity has not been specifically included with EEG classifications. Most studies have divided recordings into benign and malignant; however, some patterns within these groups may have greater prognostic significance than such broad classifications. We sought to explore reactivity, with broad classifications and subclassifications for their prognostic significance. METHODS All consecutive adults in coma who had an EEG recording performed at least 1 day after CA or during normothermia after a 24-hour mild hypothermia protocol. Outcomes were dichotomous: recovery of awareness or no recovery of awareness during hospitalization. RESULTS Twenty-nine patients met the inclusion criteria. Of the 18 patients with no reactivity, only 1 recovered awareness; of the 11 patients who demonstrated reactivity, 10 recovered awareness (sensitivity of 90% [95% confidence interval, or CI, 0.57-1] and specificity of 94% [95% CI, 0.7-1]). Of those with benign patterns, 7 recovered awareness and 1 did not; however, those patients demonstrating malignant patterns, 4 recovered and 17 did not (sensitivity of 94% [95% CI, 0.7-1] and a specificity of 63% [95% CI, 0.32-0.88]). None of the 15 patients with suppression or generalized spikes recovered consciousness, and none of these patients demonstrated reactivity. CONCLUSIONS Electroencephalogram reactivity after CA is a relatively favorable EEG feature; generalized suppression or generalized epileptiform activity, without reactivity, is associated with lack of recovery of awareness.

Seizure detection: correlation of human experts

OBJECTIVE The description and application of a new, overlap-integral comparison method and the quantification of human vs. human accuracies that can be used as goals for algorithms. METHODS Four human experts marked ten 8 h electroencephalography (EEG) records from seizure patients. The seizures varied in origin and type, including complex partial, generalized absence, secondarily generalized and primary generalized tonic-clonic. The traditional any-overlap comparison method is used in addition to the overlap-integral method, which is sensitive to the correct placement of the seizure endpoints. RESULTS The number of events marked by each reader ranged from 57 to 77. The average any-overlap sensitivity and false positives per hour rate are 0.92 and 0.117. The average overlap-integral correlation, sensitivity and specificity are 0.80, 0.82 and 0.9926. As expected, the correspondence between readers is high, but confounding issues resulted in overlap-integral sensitivities less than 0.5 for 10% of the records. Seven percent of the any-overlap sensitivities are less than 0.5. A comparison of the methods by record shows that the overlap-integral specificity and the any-overlap false positive rate measure different features. CONCLUSIONS There was little variation between readers and they were essentially interchangeable. High seizure rate (many per hour), short seizure durations (<10 s) and long seizure durations (approximately 10 min) with ambiguous offsets can complicate the analysis and result in poor correlation. There may be any number of unmarked events in rigorously marked records and it may be preferable to use records from non-epilepsy patients to compute the false positive rate. The any-overlap and overlap-integral comparison methods are complementary. SIGNIFICANCE Correlation between expert human readers can be low on some records, which will complicate testing of seizure detection algorithms.

Coma mimicking brain death following baclofen overdose.

Abstract Baclofen toxicity can be a cause of profound coma with brainstem dysfunction mimicking brain death, and is mainly a clinical diagnosis. Measuring plasma levels is not always possible and may be misleading. Imaging results are usually normal. Electroencephalography may show a pattern of burst suppression. At present no effective specific therapy is available. However, as demonstrated in our case, the prognosis can be good even in severe cases, provided it is recognized early enough, and appropriate supportive measures are instituted.

Brain blood flow in the neurological determination of death: Canadian expert report.

The neurological determination of death (NDD, brain death) is principally a clinical evaluation. However, ancillary testing is required when there are factors confounding the clinical determination or when it is impossible to complete the minimum clinical criteria. At the time of the 2003 Canadian Forum clarifying the criteria for brain death, 4-vessel cerebral angiography or radionuclide angiography were the recommended tests and the electroencephalogram was no longer supported. At the request of practitioners in the field, the Canadian Council for Donation and Transplantation sponsored the assembly of neuroradiology and neurocritical care experts to make further recommendations regarding the use of ancillary testing. At minimum, patients referred for ancillary testing should be in a deep unresponsive coma with an established etiology, in the absence of reversible conditions accounting for the unresponsiveness and the clinical examination should be performed to the fullest extent possible. For newborns, children and adults, demonstration of the absence of brain blood flow by following recommended imaging techniques fulfill the criteria for ancillary testing: 1. radionuclide angiography or CT angiography 2. traditional 4-vessel angiography 3. Magnetic resonance angiography or Xenon CT. In the absence of neuroimaging, an established cardiac arrest, as defined by the permanent loss of circulation, fulfills the ancillary criteria for the absence of brain blood flow. Acknowledging the existing limitations in this field, further research validating current or evolving techniques of brain blood flow imaging are recommended.

An Ethics of Welfare for Patients Diagnosed as Vegetative With Covert Awareness

Recent research suggests that a minority of patients diagnosed as vegetative using traditional behavioral assessments may be covertly aware. One of the most pressing concerns with respect to these patients is their welfare. This article examines foundational issues concerning the application of a theory of welfare to these patients, and develops a research agenda with patient welfare as a central focus. We argue that patients diagnosed as vegetative with covert awareness likely have sentient interests, and because sentient interests are sufficient for moral status, others have an obligation to take the welfare interests of these patients seriously. However, we do not view sentient interests as necessary for moral status, and thus it is possible that vegetative patients who lack such interests have moral status for other reasons. We propose four areas in which future research is needed to guide the ethical treatment of these patients: the assessment and management of pain; the development of quality of life assessments; end-of-life decision making; and enriching the day-to-day lives of these patients.

Ethics of neuroimaging after serious brain injury.

BackgroundPatient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to “yes” or “no” answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients.Methods/DesignOur research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients’ interests, and we explore conceptual issues in the development of a quality of life instrument adapted for neuroimaging. Project 3 will use grounded theory interviews to document families’ understanding of the patient’s condition, expectations of neuroimaging, and the impact of the results of neuroimaging. Project 4 will provide an ethical analysis of neuroimaging to investigate residual cognitive function in comatose patients within days of serious brain injury.

Human severe sepsis cytokine mixture increases β2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro

IntroductionSepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood-brain barrier dysfunction. Thus, our objectives were to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro.MethodsThe concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and 20 age- and sex-matched healthy controls employing an antibody microarray. Two CMs were prepared to mimic severe sepsis (SSCM) and control (CCM), and these CMs were then used for PMN and hCMEC/D3 stimulation in vitro. PMN adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7 dyn/cm2).ResultsEight inflammatory analytes elevated in plasma obtained from severe sepsis patients were used to prepare SSCM and CCM. Stimulation of PMN with SSCM led to a marked increase in PMN adhesion to hCMEC/D3, as compared to CCM. PMN adhesion was abolished with neutralizing antibodies to either β2 (CD18), αL/β2 (CD11α/CD18; LFA-1) or αM/β2 (CD11β/CD18; Mac-1) integrins. In addition, immune-neutralization of the endothelial (hCMEC/D3) cell adhesion molecule, ICAM-1 (CD54) also suppressed PMN adhesion.ConclusionsHuman SSCM up-regulates PMN pro-adhesive phenotype and promotes PMN adhesion to cerebrovascular endothelial cells through a β2-integrin-ICAM-1-dependent mechanism. PMN adhesion to the brain microvasculature may contribute to SAE.

The cardiac R-R variation and sympathetic skin response in the intensive care unit.

BACKGROUND AND PURPOSE The central and peripheral nervous systems are often affected in intensive care unit (ICU) patients, especially those with prolonged assisted ventilation and sepsis or systemic inflammatory response syndrome (SIRS). The autonomic nervous system, however, has been under-investigated in such patients. We evaluated autonomic nervous system (ANS) function in 29 ICU patients with various neurological disorders. METHODS Testing involved cardiac R-R variation (CRRV) as an index of parasympathetic function and the sympathetic skin response (SSR) for sympathetic assessment. RESULTS Only those 8 patients with sepsis-related neuropathy or encephalopathy had abnormal CRRV, while the SSR was absent in all but 2 patients. CONCLUSIONS Our preliminary study revealed a high incidence of autonomic dysfunction in ICU patients with various neurological disorders.