Search

This is a retrospective study to investigate the results of using zolpidem and lorazepam in persons with disorders of consciousness (DoC) and to provide practical information for clinical application and further studies. The cohort included 146 patients (11 hemorrhagic stroke, 87 traumatic brain injury (TBI), 48 anoxic brain injury (ABI)) admitted to a specialized DoC rehabilitation program. A positive trial indicated a patient responded to either zolpidem or lorazepam with prominent functional improvements necessitating routine use of the medication. Non-responders had equivocal or negative (i.e., went to sleep) responses. Eleven patients with a stroke who had either medication were all non-responders. Of the remaining 135 patients, 95 received at least one medication trial. The overall positive rate was 11.6% (11/95), with 6.3% (5/79) for zolpidem and 14.0% (6/43) for lorazepam. Among TBI patients, the positive rate of the zolpidem trial (10.2%, 5/49) was slightly higher than that of the lorazepam trial (6.9%, 2/29, p &gt, 0.05). Among ABI patients, the positive rate of the lorazepam trial (28.6%, 4/14) was significantly higher than that of the zolpidem trial (0%, 0/30, p = 0.007). Following a positive trial, most patients were continued on the medications on a regular basis before eventual discontinuation. Our results suggested the etiology of DoC, considering traumatic vs. anoxic injuries, may serve in guiding the clinical application of these medications in the treatment of DoC and in future prospective studies. We advocate for screening all patients with DoC using zolpidem and/or lorazepam.

Cardiac arrest is common and deadly. Most patients who are treated in the hospital after achieving return of spontaneous circulation still go on to die from the sequelae of anoxic brain injury. In this review, the authors provide an overview of the mechanisms and consequences of postarrest brain injury. Special attention is paid to potentially modifiable mechanisms of secondary brain injury including seizures, hyperpyrexia, cerebral hypoxia and hypoperfusion, oxidative injury, and the development of cerebral edema. Finally, the authors discuss the outcomes of cardiac arrest survivors with a focus on commonly observed patterns of injury as well as the scales used to measure patient outcome and their limitations.

Objective Recognition of potential for neurological recovery in patients who remain comatose after cardiac arrest is challenging and strains clinical decision making. Here, we utilize an approach that is based on physiological principles underlying recovery of consciousness and show correlation with clinical recovery after acute anoxic brain injury. Methods A cohort study of 54 patients admitted to an Intensive Care Unit after cardiac arrest who underwent standardized bedside behavioral testing (Coma Recovery Scale – Revised [CRS-R]) during EEG monitoring. Blinded to all clinical variables, artifact-free EEG segments were selected around maximally aroused states and analyzed using a multi-taper method to assess frequency spectral content. EEG spectral features were assessed based on pre-defined categories that are linked to anterior forebrain corticothalamic integrity. Clinical outcomes were determined at the time of hospital discharge, using Cerebral Performance Categories (CPC). Results Ten patients with ongoing seizures, myogenic artifacts or technical limitations obscuring recognition of underlying cortical dynamic activity were excluded from primary analysis. Of the 44 remaining patients with distinct EEG spectral features, 39 (88%) fit into our predefined categories. In these patients, spectral features corresponding to higher levels of anterior forebrain corticothalamic integrity correlated with higher levels of consciousness and favorable clinical outcome at the time of hospital discharge (P = 0.014). Interpretation Predicted transitions of neocortical dynamics that indicate functional integrity of anterior forebrain corticothalamic circuitry correlate with clinical outcomes in postcardiac-arrest patients. Our results support a new biologically driven approach toward better understanding of neurological recovery after cardiac arrest.

EEG testing is frequently ordered when there is a clinical suspicion of seizures or when a patient is placed on a hypothermia protocol following anoxic brain injury. Hypoxic ischemic encephalopathy...

Introduction Paroxysmal sympathetic hypersensitivity (PSH) has become more frequently recognized in patients with severe neurological brain injury. Left untreated, PSH has been associated with poor neurological outcomes. Currently, most therapeutic options are circumstantial with evidence stemming from subjective case reports. Case series Two young females were admitted after cardiac arrest and found to have anoxic brain injury with subsequent PSH. Initial treatment was targeted at relief of the hyperadrenergic symptoms, which included bromocriptine, propranolol, opioids and benzodiazepines. These therapies were minimally effective, and the patients remained comatose. After initiation of enteral baclofen treatment, they exhibited drastic reduction of PSH symptoms and became alert and interactive. After a 6-week hospital stay, they were both discharged to long-term rehabilitation centers. Conclusion This case series reviews the current therapies used for PSH and discusses 2 patients with uncontrolled PSH secondary to anoxic brain injury. Both patients arose from coma and had significant symptomatic improvement with enteral baclofen treatment. Thus, enteral baclofen should be considered as a primary treatment for PSH to prevent sustained symptoms and prolonged hospitalizations.

A critical appraisal and clinical application of Giacino JT, Whyte J, Bagiella E, et al. Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury. New England Journal of Medicine. 2012;366(9):819-826. doi: 10.1056/nejmoa1102609.

Background We evaluated computed tomography head (CTH) imaging obtained prior to targeted temperature management (TTM) in patients after cardiac arrest, and its role in prognostication. Methods In this retrospective cohort study in a tertiary-care hospital, 341 adults presenting with out-of-hospital cardiac arrest received a CTH prior to TTM. Associations between outcomes and neuroimaging variables were evaluated with Chi-square analysis for significant associations that yielded a composite neuroimaging score—Tennessee Early Neuroimaging Score (TENS). Univariable and multivariable logistic regression analysis including TENS as an independent variable and the four outcome dependent variables were analyzed. Results Four of the neuroimaging variables—sulcal effacement, partial gray-white matter effacement, total gray-white matter effacement, deep nuclei effacement—had significant associations with each of the four outcome variables and yielded TENS. In multivariable logistic regression models adjusted for potential confounders, TENS was associated with poor discharge CPC (OR 2.15, 95%CI 1.16–3.98, p = .015), poor disposition (OR 2.62, 95%CI 1.37–5.02, p = .004), in-hospital mortality (OR 1.99, 95%CI 1.09–3.62, p = .024), and ICU mortality (OR 1.89, 95%CI 1.12–3.20, p = .018). Conclusion Imaging prior to TTM may help identify post-cardiac arrest patients with severe anoxic brain injury and poor outcomes.

The severity of neuronal damages in comatose patients following anoxic brain injury can be probed by evoked auditory responses. However, it remains challenging to predict the return to full consciousness of post-anoxic coma of hospitalized patients. We presented here a method to predict the return to consciousness based on the analysis of periodic responses to auditory stimulations, recorded from surface cranial electrodes. The input data are event-related potentials (ERPs), recorded non-invasively with electro-encephalography (EEG). We extracted several novel features from the time series responses in a window of few hundreds of milliseconds from deviant and non-deviant auditory stimulations. We use these features to construct two-dimensional statistical maps, that show two separated clusters for recovered (conscience) and deceased patients, leading to a high classification success as tested by a cross-validation procedure. Finally, using Gaussian, K-neighborhood and SVM classifiers, we construct probabilistic maps to predict the outcome of post-anoxic coma. To conclude, statistics of deviant and non-deviant responses considered separately provide complementary and confirmatory predictions for the outcome of anoxic coma.

Therapeutic hypothermia (TH) is clinically used to improve neurologic outcomes in patients with anoxic brain injury after cardiopulmonary resuscitation (CPR). For patients that regress and become organ donors after neurologic determination of death (DNDDs), the impact of TH received before determination of death on organ donation outcomes remains unknown. A prospective observational study of all adult DNDDs that received CPR and had anoxia as a cause of death from March 2013 to December 2014 was conducted across 20 organ procurement organizations (OPOs) in the United States. Main outcome measures included organs transplanted per donor (OTPD), specific organ transplantation rates, and recipient graft outcomes. One thousand ninety eight DNDDs met inclusion criteria, with 46% having received TH before determination of death. DNDDs with hypothermia before death had a similar number of OTPD (2.74 vs. 2.69

Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome. Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33 °C or TTM at 36 °C for 24 h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72 h after OHCA. The primary endpoint was neurological outcome. Results: Median (quartile 1 - quartile 3) tau-A (ng/ml) values were 58 (43-71) versus 51 (43-67), 72 (57-84) versus 71 (59-82) and 76 (61-92) versus 75 (64-89) for good versus unfavourable outcome at 24, 48 and 72 h, respectively (pgroup = 0.95). Median tau C (ng/ml) values were 38 (29-50) versus 36 (29-49), 49 (38-58) versus 48 (33-59) and 48 (39-59) versus 48 (36-62) (pgroup = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48 h; tau-A: 0.51 and tau-C: 0.51). Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA.

Cardiac arrest (CA) is a sudden loss of heart function due to either a primary cardiac event such as myocardial event or secondary effect on the heart from neurological, respiratory, or metabolic causes. At the epicenter of the high mortality and morbidity from CA, is the post-cardiac arrest syndrome, which includes anoxic brain injury, myocardial dysfunction, and a systemic ischemia and reperfusion syndrome. Of these, perception of injury to the brain is the most common cause of death in two-thirds of patients with OHCA and a quarter of patients with IHCA. This chapter will review the clinical manifestation of brain injury after a cardiac arrest, the pathophysiology of brain injury in this setting, the management post-CA, and neuroprognostication of patients post-CA.

Although lithium-induced dystonia has been well documented in the literature, conflicting evidence discusses whether a patient may be susceptible to adverse effects from the drug after an anoxic brain injury. More recent literature discusses that lithium may, in fact, be neuroprotective. This case report presents a 35-year-old male who, after an anoxic brain injury after a suicide attempt, developed lithium-induced dystonia with characteristic symptoms of sustained muscle contractions, repetitive movements, and postures, which was not markedly improved with benztropine or benzodiazepines. It is postulated that because this patient received a depot neuroleptic with a subsequent anoxic brain injury, he may have become more sensitive to lithium and its rare complications.

Anoxic brain injury results after reduced or absent oxygenation of the brain tissue. Clinically it presents in a heterogeneous nature depending on the underlying etiology and severity of the anoxic event. Rehabilitation specialists typically provide support in the functional management of the brain injury. However, in some settings, acute management may also be directed by a brain rehabilitation specialist. This chapter reviews the etiology, pathophysiology, acute care, and rehabilitation management of persons with anoxic brain injury.

Introduction: Post-cardiac arrest syndrome (PCAS) is characterized by systemic ischemia/reperfusion injury, anoxic brain injury, and post-arrest myocardial dysfunction superimposed on a precipitating pathology. The role of inflammatory cytokines in cardiac arrest remains unclear. Aims: We aimed to describe, with an emphasis on clinical applications, what is known about the role of inflammatory cytokines in cardiac arrest. Data Sources: A PubMed literature review was performed for relevant articles. Only articles in English that studied cytokines in patients with cardiac arrest were included. Results: Cytokines play a crucial role in the pathogenesis of PCAS. Following cardiac arrest, the large release of circulating cytokines mediates the ischemia/reperfusion injury, brain dysfunction, and myocardial dysfunction seen. Interleukins, tumor necrosis factor, and matrix metalloproteinases all play a unique prognostic role in PCAS. High levels of inflammatory cytokines have been associated with mortality and/or poor neurologic outcomes. Interventions to modify the systemic inflammation seen in PCAS continue to be heavily studied. Currently, the only approved medical intervention for comatose patients following cardiac arrest is targeted temperature management. Medical agents, including minocycline and sodium sulfide, have demonstrated promise in animal models. Conclusions: The role of inflammatory cytokines for both short- and long-term outcomes is an important area for future investigation.

We have seen a patient with a profound, isolated, and quite selective deficit in proverb interpretation-aproverbia. The patient presented to us after an anoxic brain injury with aproverbia. Interestingly, the aproverbia appeared to be premorbid to the presenting event. Furthermore, the patient had no brain lesion that has been associated or even proposed as a cause of deficit in proverb or metaphor interpretation. The patient did have acute bilateral hippocampi lesions and associated severe anterograde amnesia, but he retained good retrograde memory with which he is able to give good, logical but concrete explanations for proverbs. This case highlights the need, importance, and interest in further neuropsychologic, imaging and functional studies of proverb and interpretation in patients and normal subjects populations.

BACKGROUND: Targeted Temperature Management (TTM) is a class I recommendation for the management of sudden cardiac arrest (SCA) patients with presumed brain injury. We aimed to study trends, predictors and outcomes in SCA patients from a nationally represented US population sample. METHODS: We utilized the National Inpatient Sample from years 2005 to 2014 for the purpose of our study. Patients with SCA and anoxic brain injury were selected using relevant ICD-9 codes. Data were analyzed for trends over the years and key outcomes were assessed. Logistic regression analysis was done to determine predictors of TTM utilization in our study population. RESULTS: A total of 78,465 patients with SCA and anoxic brain injury were identified from January 2005 to December 2014. Out of these, approximately 4,481 (5.7%) patients underwent TTM. Patients that underwent TTM were younger compared to patients without TTM utilization (60.67 vs. 63.27 years, P < 0.01). African Americans, Hispanics and women were less likely to undergo TTM. Myocardial infarction, electrolyte disorders and cardiogenic shock were associated with higher odds of TTM utilization. Sepsis, renal failure and diabetes were associated with underutilization of TTM. Inpatient mortality was higher in patients who did not undergo TTM when compared to patients who underwent TTM (67.30% vs. 65.10%, P < 0.01). CONCLUSIONS: Although TTM utilization increased over our study period, the overall application of TTM was still dismal. Factors that circumvent TTM utilization need to be addressed in future studies so more eligible patients could benefit from this life saving therapy.

While much is known about long-term survival after traumatic brain injury, less is known about survival after anoxic/hypoxic brain injury. We previously compared the two and found no significant difference (hazard ratio [HR] 0.97, p=0.92) after controlling for age, sex, and severity of disability. The present study updates this, based on 1,802 patients with TBI and 380 with anoxic, aged 15 to 25, evaluated in 1986 or later, and who survived one year post injury. The anoxic group had higher mortality (HR = 1.13), though again the difference was not statistically significant (p=0.58).

Cardiac arrest is common and deadly. Fortunately, with advances in care, short- and long-term outcomes of those resuscitated after cardiac arrest are steadily improving. Initial management focuses on general critical care support of multisystem organ dysfunction and diagnostic workup to identify the etiology of cardiac arrest. Thereafter, provision of a comprehensive bundle of care including active temperature management, coronary revascularization, delayed multimodal neurological prognostication, and best practice neurocritical care can result in a substantial proportion of patients experiencing favorable recovery despite patterns of injury once thought to be incompatible with survival.

Out-of-hospital cardiac arrest (CA) remains a leading cause of sudden morbidity and mortality; however, outcomes have continued to improve in the era of targeted temperature management (TTM). In this review, we highlight the clinical use of TTM, and provide an updated summary of multimodality monitoring possible in a modern ICU. TTM is neuroprotective for survivors of CA by inhibiting multiple pathophysiologic processes caused by anoxic brain injury, with a final common pathway of neuronal death. Current guidelines recommend the use of TTM for out-of-hospital CA survivors who present with a shockable rhythm. Further studies are being completed to determine the optimal timing, depth and duration of hypothermia to optimize patient outcomes. Although a multidisciplinary approach is necessary in the CA population, neurologists and neurointensivists are central in selecting TTM candidates and guiding patient care and prognostic evaluation. Established prognostic tools include clinal exam, SSEP, EEG and MR imaging, while functional MRI and invasive monitoring is not validated to improve outcomes in CA or aid in prognosis. We recommend that an evidence-based TTM and prognostication algorithm be locally implemented, based on each institution's resources and limitations. Given the high incidence of CA and difficulty in predicting outcomes, further study is urgently needed to determine the utility of more recent multimodality devices and studies.

BackgroundIt is unknown whether postanoxic cortical and subcortical myoclonus are distinct entities with different prognoses.MethodsIn this retrospective cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we identified 111 (18%) patients with myoclonus. Basic demographics and clinical characteristics of myoclonus were collected. EEG reports, and, when available, raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded to outcomes. Myoclonus was classified as cortical if there was a preceding, time-locked electrographic correlate and otherwise as subcortical. Outcome at discharge was determined using Cerebral Performance Category.ResultsPatients with myoclonus had longer arrests with less favorable characteristics compared to patients without myoclonus. Cortical myoclonus occurred twice as often as subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during hospitalization did not distinguish the two. Rates of electrographic seizures were higher in patients with cortical myoclonus (43%, vs 8% with subcortical). Survival to discharge was worse for patients with myoclonus compared to those without (26% vs 39%, respectively), but did not differ between subcortical and cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus were more likely to be discharged in a comatose state than those with subcortical myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at discharge was equally possible between those with cortical and subcortical myoclonus (12% and 16%, respectively).ConclusionsCortical and subcortical myoclonus are seen in every sixth patient with cardiac arrest and cannot be distinguished using clinical criteria. Either condition may have good functional outcomes.

Laryngeal fracture is a rare but potentially lethal injury. A high degree of suspicion along with an expeditious investigation is warranted to prevent airway complications. The initial assessment of the airway is vital as the patient can suffer a severe anoxic brain injury. If the patient is stable, a computed tomography (CT) scan of the neck should be obtained; this was done urgently for our patient and was managed without any extraneous intervention. We report a case of a 38-year-old man that presented to the emergency room with anterior neck pain after falling onto the back of a paintball gun. The patient was managed conservatively and favorable outcomes were obtained.

Introduction Serum neuron-specific enolase (NSE) levels have been shown to correlate with neurologic outcome in comatose survivors of cardiac arrest but use of absolute NSE thresholds is limited. This study describes and evaluates a novel approach to analyzing NSE, the NSE ratio, and evaluates the prognostic utility of NSE absolute value thresholds and trends over time. Methods 100 consecutive adult comatose cardiac arrest survivors were prospectively enrolled. NSE levels were assessed at 24, 48, and 72 h post-arrest. Primary outcome was the Glasgow Outcome Score (GOS) at 6 months post-arrest; good outcome was defined as GOS 3–5. Absolute and relative NSE values (i.e. the NSE ratio), peak values, and the trend in NSE over 72 h were analyzed. Results 98 patients were included. 42 (43%) had a good outcome. Five good outcome patients had peak NSE >33 µg/L (34.9–46.4 µg/L). NSE trends between 24 and 48 h differed between outcome groups (decrease by 3.0 µg/L (0.9–7.0 µg/L) vs. increase by 13.4 µg/L (−3.7 to 69.4 µg/L), good vs. poor, p = 0.004). The 48:24 h NSE ratio differed between the good and poor outcome groups (0.8 (0.6–0.9) vs. 1.4 (0.8–2.5), p = 0.001), and a 48:24 h ratio of ≥1.7 was 100% specific for poor outcome. Conclusions The NSE ratio is a unique method to quantify NSE changes over time. Values greater than 1.0 indicate increasing NSE and may be reflective of ongoing neuronal injury. The NSE ratio obviates the need for an absolute value cut-off.

Pseudohypoxic brain swelling (or the more recent term, postoperative intracranial hypotension-associated venous congestion) is a rare and potentially deadly complication that can occur after routine spine or brain surgery. The mechanism of this injury has been described as a rapid cerebral spinal fluid drainage leading to venous cerebral congestion. The clinical and radiographic findings mimic those found in a patient who has suffered an anoxic brain injury. We present the third reported case of postoperative intracranial hypotension-associated venous congestion following spinal surgery.

Stroke is a major cause of neurological disability and death in industrialized nations. Therapeutic hypothermia has been shown to protect the brain from ischemia, stroke, and other acute neurological insults at the laboratory level. It has been shown to improve neurological outcome in certain clinical settings including anoxic brain injury due to cardiac arrest and hypoxic-ischemic neonatal encephalopathy. Hypothermia seems to affect multiple aspects of brain physiology and it is likely that multiple mechanisms underlie its protective effect. Understanding the events that occur in the ischemic brain during hypothermia might help lead to an understanding of how to protect the brain against acute injuries.

Anoxic encephalopathy is frequently encountered in the medical intensive care unit (ICU). Cerebral edema as a result of anoxic brain injury can result in increased attenuation in the basal cisterns and subarachnoid spaces on computerized tomography (CT) scans of the head. These findings can mimic those seen in acute subarachnoid hemorrhage (SAH) and are referred to as pseudosubarachnoid hemorrhage (pseudo-SAH). Pseudo-SAH is a diagnosis critical care physicians should be aware of as they treat and evaluate their patients with presumed SAH, which is a medical emergency. This lack of awareness could have important clinical implications on outcomes and impact management decisions if patients with anoxic brain injury are inappropriately treated for SAH. We describe three patients who presented to the hospital with anoxic brain injury. Subsequent CT head suggested SAH, which was subsequently proven to be pseudo-SAH.