Functional Neuroimaging as an Assessment Tool in Critically Ill Patients.

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.

Detection of Atrial Fibrillation in Routine EEG Recordings.

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.

Seizures in anti-Hu-associated extra-limbic encephalitis: Characterization of a unique disease manifestation.

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.

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.

Isoflurane Use in the Treatment of Super-Refractory Status Epilepticus is Associated with Hippocampal Changes on MRI.

BACKGROUND: Refractory status epilepticus (RSE) is associated with high morbidity and mortality. Experts recommend aggressive management with continuous intravenous infusions or inhaled anesthetics such as isoflurane. However, there is concern that MRI changes in RSE reflect isoflurane neurotoxicity. We performed a case-control study to determine whether isoflurane is neurotoxic, based on MRI signal changes. METHODS: We performed a retrospective case-control study of the incidence of MRI changes in RSE treated with and without isoflurane. Charts were reviewed for demographic and treatment information. T1, T2, and FLAIR sequences of MRIs were reviewed independently by two neuroradiologists blinded to treatment group for presence or absence of signal change or atrophy in the meninges, cortex, white matter, basal ganglia, thalamus, hippocampus, brainstem, and cerebellum. RESULTS: Eight cases of RSE receiving treatment with isoflurane were identified and double-matched with 15 controls who received only intravenous anesthetics. Baseline characteristics were similar. Hippocampal signal change was observed more frequently in cases receiving isoflurane (p = 0.026). CONCLUSIONS: Hippocampal signal changes were associated with isoflurane use in patients with RSE. They were also associated with number of seizure days prior to MRI and the use of multiple anesthetic agents. Similar changes have been seen as a result of RSE itself, and one cannot rule out the possibility these changes represent seizure-related effects. If isoflurane-related, these hippocampal signal changes may be the result of a direct neurotoxic effect of prolonged isoflurane use or failure of isoflurane to protect the hippocampus from seizure-induced injury despite achieving electrographic burst-suppression.

Added Value of MRI over CT of the Brain in Intensive Care Unit Patients.

BACKGROUND: Intensive care unit (ICU) patients with neurological impairments often require neuroimaging. However, the relative sensitivity of various imaging modalities of the brain has not yet been explored in this population. METHODS: In this study, we compare the findings of CT and MRI scans in ICU patients to (1) identify the number and rate of clinically relevant lesion detected by MRI while missed by CT and vice versa and (2) determine specific lesion types for which CT versus MRI discrepancies exist. A review of medical records included CT and MRI reports of patients who underwent these procedures while they were patients in our ICUs between July 2004 and July 2009. MRI and CT were compared regarding their ability to detect clinically relevant abnormalities. Odds ratios with 95% confidence limits were calculated to compare diagnostic categories regarding the rate of discrepant MRI versus CT findings, followed by power analyses to estimate sample sizes necessary to allow for further testing in a larger trial. RESULTS: MRI revealed clinically relevant additional abnormalities over CT in 129 of 136 patients (95%) that included the detection of additional finding for 15/27 hemorrhagic lesions (55.6%), 33/36 (92%) ischemic strokes, 19/27 (70%) traumatic lesions, 8/14 (57%) infections, 15/24 (62.5%) metabolic abnormalities, and all seven neoplasms. Odds ratio analysis revealed the added sensitivity of MRI to be greater for ischemic and neoplastic lesions than for trauma, metabolic-related abnormalities, infection, or hemorrhage. CONCLUSIONS: MRI is more sensitive than CT in identifying clinically meaningful lesions in at least a subset of ICU patients, regardless of pathology.

Giant Somatosensory Evoked Potentials Coincident With Epileptiform Discharges in Acutely Comatose Patients.

BACKGROUND: The amplitude of the cortically generated somatosensory evoked potential (SSEP) is used to predict outcome in comatose patients. The relationship between epileptiform discharges and SSEP amplitude has not been elucidated in those patients. METHODS: Bilateral median nerve SSEP and electroencephalograph (EEG) studies were performed in a comatose patient (patient 1) 1 day after cardiac surgery and repeated 4 days later. He had tranexamic acid administered before and during surgery. Another comatose patient (patient 2) had the same studies performed 1 day after sustaining 10 minutes of pulseless electrical cardiac activity. RESULTS: Both comatose patients had epileptiform discharges (on EEG) that were coincident with giant cortically generated SSEPs. In patient 1, the EEG and SSEP studies repeated 5 days postoperatively showed no epileptiform discharges, and the cortically generated SSEP amplitude was decreased (normalized) compared with that obtained one day postoperatively. He emerged from coma and had a good recovery. Patient 2 died shortly after EEG and SSEP testing. CONCLUSIONS: Epileptiform discharges were associated with giant cortically generated median nerve SSEP amplitude (tranexamic acid was implicated in patient 1 and anoxic brain injury in patient 2). Accordingly, those who use the amplitude of cortically generated SSEPs for predicting outcome in comatose patients should consider the presence of epileptiform discharges (detected by EEG) as a potential confounding factor.

Positive prognostication from median-nerve somatosensory evoked cortical potentials.

BACKGROUND: The 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. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: While 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.

A prospective observational study of seizures after cardiac surgery using continuous EEG monitoring.

INTRODUCTION: Recently, there have been several retrospective reports suggesting an increased frequency in seizures after cardiopulmonary bypass, associated with increased patient morbidity. We sought to prospectively investigate the incidence of electrographic seizures without clear convulsive clinical correlates and subsequent neurologic injury following cardiac surgery. METHODS: This single-center, prospective, observational study used continuous subhairline electroencephalographic (cEEG) monitoring in the intensive care unit following routine cardiac surgery, ranging from coronary bypass surgery to complex aortic arch reconstruction. The primary outcome was the proportion of patients developing postoperative seizures, as confirmed on cEEG monitoring. Secondary outcomes included neurologic injury, post-operative complications, mortality, and ICU and hospital lengths of stay. RESULTS: 101 consenting patients were included and 3 patients had seizures (2 focal and convulsive, 1 generalized and electrographic). All three patients with seizures were ≥65 years old, had "open-chamber" procedures, and had cardiopulmonary bypass times >120 min. One of the 3 patients with seizures was exposed to higher doses of tranexamic acid. None of the patients with seizures had permanent neurologic sequelae and all were doing well at 1-year follow-up. There was no increased morbidity or mortality in patients with seizures. CONCLUSIONS: Electrographic seizures occur infrequently after cardiac surgery and are generally associated with a good prognosis. Prophylactic cEEG monitoring is unlikely to be cost-effective in this population. (ClinicalTrials.gov Identifier: NCT01291992).

Crossed cerebro-cerebellar atrophy with Dyke Davidoff Masson syndrome.

Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult. It has characteristics of clinical and radiological changes. These changes include hemiparesis, seizures, facial-asymmetry, and mental retardation. We present a 25-year-old man with crossed cerebrocerebellar atrophy and DDMS. His seizures were well controlled using a combination of antiepileptic drugs.

New guidelines for the initial management of head injury.

The majority of patients presenting with mild head trauma will have no intracranial pathology and can be safely discharged home. It is estimated that 10% to 15% of these patients will have clinically significant findings on computed tomography imaging and up to 1% may require neurosurgical intervention. The revised Scandinavian Head Trauma Guidelines provide an evidence- and consensus-based algorithm to assist physicians in determining which patients presenting with minimal, mild or moderate blunt head injury are at higher risk for intracranial pathology and thus require neuroimaging and hospital admission. Striking a balance between health care costs and risk of morbidity remains an ongoing challenge and we will present our concerns with this useful, but conservative management algorithm.

Sleeping well.

In a study by Cruse et al. published in BMC Medicine, patients with severe brain damage who were in the Vegetative or Minimally Conscious States (VS or MCS, respectively) from traumatic and nontraumatic etiologies had assessments of circadian rhythms using an actigraph, a device worn on a limb to evaluate circadian rhythmicity, in this population. This is a novel approach and is being used as a surrogate for polysomnography and other reference standards. Cruse et al. showed more disruption in circadian rhythms in the VS when compared to the MCS. This suggests that more brain injury occurs in the areas that control circadian rhythmicity in VS than in MCS patients. The study provides opportunities for improved prognostication and rehabilitation strategies in this patient population.

The evidence-based medicine paradigm: where are we 20 years later? Part 1.

The evidence-based medicine (EBM) paradigm, introduced in 1992, has had a major and positive impact on all aspects of health care. However, widespread use has also uncovered some limitations; these are discussed from the perspectives of two clinicians in this, the first of a two part narrative review. For example, there are credible reservations about the validity of hierarchical levels of evidence, a core element of the EBM paradigm. In addition, potential and actual methodological and statistical deficiencies have been identified, not only in many published randomized controlled trials but also in systematic reviews, both rated highly for evidence in EBM classifications. Ethical violations compromise reliability of some data. Clinicians need to be conscious of potential limitations in some of the cornerstones of the EBM paradigm, and to deficiencies in the literature.

The evidence-based medicine paradigm: where are we 20 years later? Part 2.

In Part 2, we discuss the challenges of keeping up with the 'literature,' evidence-based medicine (EBM) in emerging economies and the Neurosciences, and two recent approaches to classifying evidence. We conclude by summarizing information from Parts 1 and 2 which suggest the need to critically re-appraise core elements of the EBM paradigm: (1) the hierarchical ranking of evidence, (2) randomized controlled trials or systematic reviews as the gold standard for all clinical questions or situations, (3) the statistical tests that have become integral to the 'measurements' for analyzing evidence, and (4) re-incorporating a role for evidence from basic sciences and pathophysiology. An understanding of how cognitive processes influence clinical decisions is also necessary to improve evidence-based practice. Emerging economies may have to modify the design and conduct of clinical research to their settings. Like all paradigms, EBM must keep improving with input from the grassroots to remain beneficial.

Acute fulminant hepatic failure, encephalopathy and early CT changes.

BACKGROUND: Acute fulminant hepatic failure (AFHF) is common in tertiary care centres with transplant facilities. Cerebral edema frequently threatens the lives of such patients. We reviewed our cases of AFHF, noting the incidence of cerebral edema with serial CT scans and factors associated with mortality. METHODS: Patients were captured through HmRI classification of acute liver/hepatic failure. Chart review included tabulation of: demographics, INR; serum bilirubin, creatinine, albumin; in-hospital mortality. Computed tomogram (Ct) scans were re-read with blinding to clinical information and catalogued for changes in sulcal markings, ventricular size and grey-white differentiation (GWD). INCLUSION CRITERIA: age equal to or greater than 16 years, encephalopathy, hepatic failure within eight weeks of onset of liver disease, CT scans of head performed. RESULTS: Of our 25 cases with AFHF, acetaminophen toxicity was the most common etiology (nine cases). Twelve of the 25 patients (48%) had cerebral edema on CT, including eight of the nine (89%) with acetaminophen toxicity. Decrease in sulcal markings and ventricular size preceded conspicuous alterations in GWD. Fourteen died, including all 12 with cerebral edema, although death was due to herniation in only one patient. None of the hematological or biochemical variables correlated significantly with mortality. CONCLUSIONS: Acetaminophen toxicity is a common cause of AFHF; this combination has a strong association with cerebral edema. Cerebral edema can be detected in its early stages and followed by baseline and serial CT scans. This facilitates management to prevent fatal brain herniation.

Status epilepticus: a review, with emphasis on refractory cases.

Status epilepticus is among the most dramatic of clinical presentations encountered by emergency room physicians, neurologists, neurosurgeons and intensivists. While progress in its management has been aided significantly with an increasing number of effective treatment options, improved diagnostic methods and more effective monitoring, poor outcomes and diagnostic failures are still frequently encountered. Refractory cases still carry significant morbidity and mortality rates, including poor cognitive outcomes. This review discusses basic pathophysiology and management of status epilepticus, neuroimaging findings, the role of continuous electroencephalogram monitoring and nonconvulsive status epilepticusas well as recent developments in treatment options for refractory cases.

Bickerstaff's brainstem encephalitis presenting to the ICU.

BACKGROUND: Bickerstaff's brainstem encephalitis continues to pose a diagnostic and treatment challenge since the original descriptions by Bickerstaff and Miller-Fisher. The clinical syndrome overlaps with AIDP and MFS, but is accompanied by decreased level of consciousness not attributable to other causes, and the variable presence of long-tract signs. METHODS: The methods in this study include the case presentation with autopsy findings of an elderly male presented with progressive weakness and impairment of consciousness and the literature review. RESULTS: Examination revealed areflexia and loss of most brainstem reflexes. Some improvement occurred after several weeks in the ICU, prior to death from pulmonary embolism. Pathologic specimens were similar to others in the literature, with inflammatory changes in nerve roots and brainstem. CONCLUSIONS: The above findings led us to conclude that Bickerstaff's brainstem encephalitis remains a clinical diagnosis despite advances in electrophysiologic testing and neuroimaging. BBE likely represents part of a spectrum, overlapping with AIDP and MFS. Immunomodulation may be helpful in shortening the clinical course.