Teneille Gofton

New-onset refractory status epilepticus Etiology, clinical features, and outcome

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation.

Functional MRI study of the primary somatosensory cortex in comatose survivors of cardiac arrest

It is difficult to assess cerebral function in comatose patients. Because earlier functional neuroimaging studies demonstrate associations between cerebral metabolism and levels of consciousness, fMRI in comatose survivors of cardiac arrest could provide further insight into cerebral function during coma. Using fMRI, cerebral activation to somatosensory stimulation to the palm of the hand was measured in 19 comatose survivors of cardiac arrest and in 10 healthy control subjects and was compared to somatosensory-evoked potential (SSEP) testing of the median nerve. Changes in the blood oxygenation-level dependent signal (BOLD) in the primary somatosensory cortex (S1) contralateral to the stimulated hand were quantified. Clinical outcome was assessed using the Glasgow Outcome Scale (GOS) and the modified Rankin Scale at 3 months post-cardiac arrest. Five out of 19 patients were alive at 3 months. Patients who survived cardiac arrest showed greater BOLD in S1 contralateral to somatosensory stimulation of the hand compared to patients who eventually did not. Greater BOLD was also seen in S1 of patients who retained their SSEP N20 waveforms. There were also positive correlations between BOLD in S1 with both levels of consciousness and measures of outcome at 3 months. In summary, this study demonstrates that BOLD in the S1 contralateral to somatosensory stimulation of the hand varies with clinical measures of the level of consciousness during coma.

Misdiagnosis of epileptic seizures as manifestations of psychiatric illnesses.

BACKGROUND Epileptic seizures may be misdiagnosed if they manifest as psychiatric symptoms or seizures occur in patients with known psychiatric illness. METHODS We present clinical profiles of six patients with epilepsy (three male, mean age 39 ± 12 years) that presented with prominent psychiatric symptoms. RESULTS Two patients had pre-existing psychiatric illnesses. Three patients were initially diagnosed with panic attacks, two with psychosis, and one with schizophrenia. Five patients had temporal lobe epilepsy (TLE) while the sixth patient was subsequently found to have absence status epilepticus (SE). Cranial computed tomogram (CT) including contrast study was unremarkable in five patients and showed post-traumatic changes in one patient. Cranial magnetic resonance imaging (MRI) revealed dysembryoplastic neuroepithelial tumour (DNET) in one patient, cavernous hemangioma in one, and post-traumatic changes plus bilateral mesial temporal sclerosis in another patient but it was normal in two TLE patients. Routine electroencephalography (EEG) revealed absence SE in one patient but it was non-diagnostic in the TLE patients. Video-EEG telemetry in the epilepsy monitoring unit (EMU) was necessary to establish the diagnosis in four TLE patients. None of the patients responded to medications aimed at treating psychiatric symptoms alone. Two patients required surgery while the other four required treatment with anti-epileptic drugs. All the patients had favorable response to the treatment of their epilepsy. CONCLUSIONS This case series illustrates that epileptic patients may experience non-convulsive seizures that might be mistaken as primary psychiatric illnesses. In this subset of patients, evaluation by an epileptologist, MRI of the brain, and/or video-EEG telemetry in an EMU was necessary to confirm the diagnosis of epilepsy if routine EEGs and cranial CT are normal.

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.

Positive Prognostication from Median-Nerve Somatosensory Evoked Cortical Potentials

BackgroundThe bilateral absence of the cortical N20 median-nerve somatosensory evoked potential (SSEP) is a strong predictor of poor outcome from coma. However, when N20s are present, accurate prognostication is challenging. Here, we investigated the potential for later SSEP components to help disambiguate outcome in these cases.MethodsIn a retrospective review of data from two intensive care units, the amplitudes and latencies of the N20, P25, and N35 components of 28 patients in coma were quantified and related to outcome at discharge from primary care (average 1-month post-injury). Only patients who had survived primary care were included in order to avoid self-fulfilling prophecies, and to focus outcome prediction on those patients with relatively present SSEPs.ResultsThe amplitudes of the N20 and N35 components (averaged across hemispheres) significantly predicted the range of outcomes beyond death. Abnormal amplitudes of the N20 and N35—as derived from a healthy control group—were significantly associated with poor outcome. The relative latencies of the cortical components were not related to outcome.ConclusionsWhile it is well documented that absent SSEPs are highly predictive of poor outcome, the current data indicate that the relative preservation (absolute amplitude) of “present” N20 and N35 SSEP components can also provide predictive value and thereby inform clinicians and families with decision-making in coma. Further prospective study will elucidate the relative contributions of etiology to the predictive power of these SSEP measures.

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.

A palliative approach to neurological care: a literature review.

This review assesses the current opinion towards early palliative care in neurology and discusses the existing evidence base. A comprehensive literature search resulted in 714 publications with 53 being directly relevant to the scope of this review. The current literature reflects primarily expert opinion and describes a growing interest in the early introduction of palliative principles into neurological care. Early initiation of palliative interventions has the potential to improve quality of life, enhance symptom management and assist in advance care planning. Further data is required to determine whether this shift in philosophy has a positive impact on patient care.

Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.

We convened an international group of experts to standardize definitions of New‐Onset Refractory Status Epilepticus (NORSE), Febrile Infection‐Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in‐person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion‐Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super‐refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.

Electroencephalographic Recordings During Withdrawal of Life-Sustaining Therapy Until 30 Minutes After Declaration of Death

BACKGROUND The timing of the circulatory determination of death for organ donation presents a medical and ethical challenge. Concerns have been raised about the timing of electrocerebral inactivity in relation to the cessation of circulatory function in organ donation after cardio-circulatory death. Nonprocessed electroencephalographic (EEG) measures have not been characterized and may provide insight into neurological function during this process. METHODS We assessed electrocortical data in relation to cardiac function after withdrawal of life-sustaining therapy and in the postmortem period after cardiac arrest for four patients in a Canadian intensive care unit. Subhairline EEG and cardio-circulatory monitoring including electrocardiogram, arterial blood pressure (ABP), and oxygen saturation were captured. RESULTS Electrocerebral inactivity preceded the cessation of the cardiac rhythm and ABP in three patients. In one patient, single delta wave bursts persisted following the cessation of both the cardiac rhythm and ABP. There was a significant difference in EEG amplitude between the 30-minute period before and the 5-minute period following ABP cessation for the group, but we did not observe any well-defined EEG states following the early cardiac arrest period. CONCLUSIONS In a case series of four patients, EEG inactivity preceded electrocardiogram and ABP inactivity during the dying process in three patients. Further study of the electroencephalogram during the withdrawal of life sustaining therapies will add clarity to medical, ethical, and legal concerns for donation after circulatory determined death.

Bowel Ischemia in Refractory Status Epilepticus: Report of Two Cases and Review of the Literature

BackgroundBowel ischemia is a rare life threatening complication seen in patients with refractory status epilepticus (RSE). The few reported cases of bowel ischemia in this setting have been associated with the use continuous barbiturate infusions. We report two patients with RSE in the absence of barbiturate infusion and without clear structural, infectious, anatomic, vascular, or autoimmune etiology. We review the clinical details of the cases and potential factors involved in the development of non-occlusive bowel ischemia in patients with RSE.MethodsThe following is a retrospective review of two cases of non-occlusive mesenteric ischemia that occurred during the management of RSE. The clinical data and the details of pathological examination of the infarcted segments of bowel are presented in both cases.ResultsIn both cases, the bowel ischemia occurred in the absence of barbiturate infusion or evidence of clear thrombosis, infection, or autoimmune etiology. Case 1 had extensive ischemic necrosis of the small bowel with secondary pseudomembrane formation, and case 2 had full thickness infarction of both the large and small bowel.ConclusionsThe mechanism of bowel infarction in these cases is likely multifactorial and was not associated with barbiturate use. Likely contributors to ischemia include RSE itself, systemic hypotension, vasopressor use, general anesthesia, and abnormal cardiac function. During the management of RSE, every effort must be made to avoid the secondary complications such as bowel ischemia.