Background

Therapeutic hypothermia (TH) improves outcomes in comatose patients resuscitated from cardiac arrest. However, nonconvulsive status epilepticus (NCSE) may cause persistent coma. The frequency and timing of NCSE after cardiac arrest is unknown.

Methods

Review of consecutive subjects treated with TH and receiving continuous EEG (cEEG) monitoring between 8/1/2009 and 11/16/2010. Demographic data, survival, and functional outcome were prospectively recorded. Each cEEG file was analyzed using standard definitions to define NCSE. Data were analyzed using descriptive and non-parametric statistics.

Results

Mean age of the 101 subjects was 57 years (SD 15) with most subjects being male (N = 55, 54%) and experiencing out-of-hospital cardiac arrest (N = 78; 77%). Ventricular fibrillation was the initial cardiac rhythm in 39 (38%). All subjects received TH. Thirty subjects (30%) awoke at a median of 41 h (IQR 30, 61) after cardiac arrest. A total of 29/30 (97%) subjects surviving to hospital discharge were awake. Median interval from arrest to placement of cEEG was 9 h (IQR 6, 12), at which time the mean temperature was 33.9°C. NCSE occurred in 12 (12%) subjects. In 3/12 (25%) subjects, NCSE was present when the cEEG recording began. In 4 subjects, NCSE occurred within 8 h of cEEG recording. One (8%) subject with NCSE survived in a vegetative state.

Conclusions

NCSE is common in comatose post-cardiac arrest subjects receiving TH. Most seizures occur within the first 8 h of cEEG recording and within the first 12 h after resuscitation from cardiac arrest. Outcomes are poor in those who experience NCSE.

The December 2003 report from the National Institute of Neurological Disorders and Stroke (NINDS) Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) recommended clinical trials for evaluation of blood pressure management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertensive response in ICH. To address important gaps in knowledge, we conducted a pilot study funded by the NINDS, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) I Trial, during 2004–2008 to determine the appropriate level of systolic blood pressure (SBP) reduction. We now have initiated a multicenter, randomized Phase III trial, the ATACH II Trial, to definitively determine the efficacy of early, intensive, anti-hypertensive treatment using intravenous (IV) nicardipine initiated within 3 h of onset of ICH and continued for the next 24 h in subjects with spontaneous supratentorial ICH. The primary hypothesis of this large (N = 1,280), streamlined, and focused trial is that SBP reduction to ≤140 mm Hg reduces the likelihood of death or disability at 3 months after ICH, defined by modified Rankin scale score of 4–6, by at least 10% absolute compared to standard SBP reduction to ≤180 mm Hg. The ATACH II trial is a natural extension of numerous case series, the subsequent ATACH I pilot trial, and a preliminary, randomized, and controlled trial in this patient population funded by the Australian National Health and Medical Research Council. Both trials recently confirmed the safety and tolerability of both the regimen and goals of antihypertensive treatment in acutely hypertensive patients with ICH, as proposed in the present trial. The underlying mechanism for this expected beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 73% of the patients with acute ICH. The Australian trial provided preliminary evidence of attenuation of hematoma expansion with intensive SBP reduction. The ATACH II trial will have important public health implications by providing evidence of, or lack thereof, regarding the efficacy and safety of acute antihypertensive treatment in subjects with ICH. This treatment represents a strategy that can be made widely available without the need for specialized equipment and personnel, and therefore, can make a major impact upon clinical practice for treating patients with ICH.

Background

Intracranial pressure (ICP) remains a pivotal physiological signal for managing brain injury and subarachnoid hemorrhage (SAH) patients in neurocritical care units. Given the vascular origin of the ICP, changes in ICP waveform morphology could be used to infer cerebrovascular changes. Clinical validation of this association in the setting of brain trauma, and SAH is challenging due to the multi-factorial influences on, and uncertainty of, the state of the cerebral vasculature.

Methods

To gain a more controlled setting, in this articel, we study ICP signals recorded in four uninjured patients undergoing a CO2 inhalation challenge in which hypercapnia induced acute cerebral vasodilatation. We apply our morphological clustering and analysis of intracranial pressure (MOCAIP) algorithm to identify six landmarks on individual ICP pulses (based on the three established ICP sub-peaks; P1, P2, and P3) and extract 128 ICP morphological metrics. Then by comparing baseline, test, and post-test data, we assess the consistency and rate of change for each individual metric.

Results

Acute vasodilatation causes consistent changes in a total of 72 ICP pulse morphological metrics and the P2 sub-region responds to cerebral vascular changes in the most consistent way with the greatest change as compared to P1 and P3 sub-regions.

Conclusions

Since the dilation/constriction of the cerebral vasculature resulted in detectable consistent changes in ICP MOCIAP metrics, by an extended monitoring practice of ICP that includes characterizing ICP pulse morphology, one can potentially detect cerebrovascular changes, continuously, for patients under neurocritical care.

Background

Elevated levels of B-type natriuretic peptide (BNP) have been associated with cardiac dysfunction and adverse neurological outcomes after subarachnoid hemorrhage (SAH). We sought to determine whether elevated levels of BNP are independently associated with radiographic cerebral infarction after SAH.

Methods

Plasma BNP levels were measured after admission, a mean of 5.5 ± 3.0 days after SAH onset. Cerebral infarction was determined by retrospective review of computerized tomography (CT) scans. Cerebral vasospasm was confirmed by the presence of vascular narrowing on cerebral angiogram. The association between BNP and cerebral infarction was quantified using multivariable logistic regression and reverse stepwise elimination of clinical covariates. A stratified analysis was performed to quantify the association between BNP levels and infarction in patients with and without angiographic vasospasm.

Results

BNP levels were measured from 119 subjects. The median BNP level was 105 pg/ml (interquartile range 37–275 pg/ml). In our multivariable model, the top quartile of BNP levels (≥276 pg/ml) were associated with an increased odds of cerebral infarction (OR 4.2, P = 0.009). The stratified analysis showed that the association between BNP and infarction was strongest in patients without angiographic vasospasm (OR 7.8, P = 0.006).

Conclusions

Elevated levels of BNP are strongly and independently associated with cerebral infarction, and the association is most pronounced in patients without angiographic vasospasm. These results provide further evidence that other mechanisms can contribute to infarction, and BNP may be a useful biomarker in detecting patients at risk for adverse outcomes without large vessel vasospasm.

Background

We describe institutional vasopressor usage, and examine the effect of vasopressors on hemodynamics: heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PbtO2), and jugular venous oximetry (SjVO2) in adults with severe traumatic brain injury (TBI).

Methods

We performed a retrospective analysis of 114 severely head injured patients who were admitted to the neurocritical care unit of Level 1 trauma center and who received vasopressors (phenylephrine, norepinephrine, dopamine, vasopressin or epinephrine) to increase blood pressure

Results

Phenylephrine was the most commonly used vasopressor (43%), followed by norepinephrine (30%), dopamine (22%), and vasopressin (5%). Adjusted for age, gender, injury severity score, vasopressor dose, baseline blood pressure, fluid administration, propofol sedation, and hypertonic saline infusion, phenylephrine use was associated with 8 mmHg higher mean arterial pressure (MAP) than dopamine (P = 0.03), and 12 mmHg higher cerebral perfusion pressure (CPP) than norepinephrine (P = 0.02) during the 3 h after vasopressor start. There was no difference in ICP between the drug groups, either at baseline or after vasopressor treatment.

Conclusions

Most severe TBI patients received phenylephrine. Patients who received phenylephrine had higher MAP and CPP than patients who received dopamine and norepinephrine, respectively.

Background

Continuous EEG (cEEG) monitoring is being used with increasing frequency in critically ill patients, most often to detect non-convulsive seizures. While cEEG is non-invasive and feasible in the critical care setting, it is also expensive and labor intensive, and there has been little study of its impact on clinical care. We aimed to determine prospectively the impact of cEEG on clinical management in critically ill children.

Methods

Critically ill children (non-neonates) with acute encephalopathy underwent cEEG. Study enrollment and data collection were prospective.

Results

100 children were studied. EEG monitoring led to specific clinical management changes in 59 children. These included initiating or escalating anti-seizure medications in 43 due to seizure detection, demonstrating that a specific event (subtle movement or vital sign change) was not a seizure in 21, or obtaining urgent neuroimaging that led to a clinical change in 3. In the remaining 41 children, cEEG ruled out the presence of non-convulsive seizures but did not lead to a specific change in clinical management.

Conclusions

EEG monitoring led to changes in clinical management in the majority of patients, suggesting it may have an important role in management of critically ill children. Further study is needed to determine whether the management changes elicited by cEEG improve outcome.

Background

Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathogenesis of vasospasm and delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. The aim of this study was to investigate the relationship between cerebrospinal fluid (CSF) ET-1 levels and angiographic vasospasm and DCI.

Methods

Patients with aSAH were consented (n = 106). Cerebral vasospasm was determined by angiography. DCI was determined by transcranial Doppler (TCD) results and/or angiogram results with corresponding clinical deterioration. CSF ET-1 levels over 14 days after the initial insult was quantified by ELISA. ET-1 analysis included a group-based trajectory analysis and ET-1 exposure rate during 24, 48, and 72 h prior to, as well as 72 h post angiography, or clinical deterioration.

Results

Trajectory analysis revealed two distinct groups of subjects with 56% of patients in the low ET-1 trajectory group (mean at day 1 = 0.31 pg/ml; SE = 0.04; mean at day 14 = 0.41 pg/ml; SE = 0.15) and 44% of patients in the high ET-1 trajectory group (mean at day 1 = 0.65 pg/ml; SE = 0.08; mean at day 14 = 0.61 pg/ml; SE = 0.06). Furthermore, we observed that ET-1 exposure rate 72 h before angiography and clinical spasm was a significant predictor of both angiographic vasospasm and DCI, whereas, ET-1 exposure after angiography and clinical spasm was not associated with either angiographic vasospasm or DCI.

Conclusion

Based on these results we conclude that ET-1 concentrations are elevated in a sub-group of patients and that the acute (72 h prior to angiography and clinical neurological deterioration), but not chronic, elevations in CSF ET-1 concentrations are indicative of the pathogenic alterations of vasospasm and DCI in aSAH patients.

Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action. We demonstrated the feasibility of thrombolysis combined with endovascular hypothermia, but not all patients achieved effective cooling. We sought to identify the factors that determined effective cooling.

Methods

In 26 patients who underwent endovascular hypothermia we computed 4 measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC) 34 ratio; AUC-34; and AUC-35. Using multivariate regression, we examined the effects of age, weight, starting temperature, body mass index, body surface area (BSA) , gender, shivering, and total meperidine dose on the 4 outcome measures.

Results

In univariate analyses, all 4 outcome measures were significantly influenced by BSA (p<0.01 in all univariate analyses). Time to reach target temperature was quicker in older patients (p<0.01). Shivering and meperidine dose were highly intercorrelated (r=0.6, p<0.01) and both marginally influenced all 4 outcome measures. In multivariate analysis, AUC ratio and time to reach target temperature were significantly influenced by BSA (p<0.01) and meperidine (p<0.05); AUC-34 was influenced only by BSA (p<0.01). The AUC- 35 was influenced by BSA (p<0.01), shivering, and total meperidine dose (p<0.05).

Conclusions

The most important determinant of effective cooling during endovascular hypothermia is BSA; larger patients are more difficult to cool and maintain in therapeutic range. Older patients cool more quickly. Shivering was well controlled by the combination of meperidine, buspirone, and surface counter-warming and only minimally influenced cooling effectiveness. Future trials of therapeutic hypothermia may include added measures to cool larger patients more effectively.

Background

The prototypical intracranial pressure (ICP) pulse morphology has been well known to be triphasic. Several studies suggest that the morphology of ICP pulse reflects the physiological and pathophysiological conditions of the intracranial dynamics. Recently, there has been a renaissance of studying ICP pulse using new ICP signal processing technologies in various clinical contexts. Cerebral blood flow velocity (CBFV) pulse is another important pulsatile signal originated from the complex circulatory systems of cerebral blood flow. However, CBFV pulse morphology has not been well studied mainly due to the noise level and lack of signal processing techniques.

Methods

Our group recently developed a technique called the Morphological Clustering and Analysis of Intracranial Pressure (MOCAIP) that can extract a comprehensive set of pulse morphological metrics. We extend this algorithm to extract various morphological metrics from ICP and CBFV pulses that were simultaneously recorded from 47 brain injury patients and investigate the mutual correlation between those metrics utilizing the robust percentage bend correlation analysis.

Results

Our results show that CBFV pulses are also triphasic as ICP pulses and 15.2% of 128 pulse morphological metrics extracted from ICP and CBFV pulses are highly correlated (p<0.01) in an inter-subject fashion. In addition, mean ICP does not correlate (p=0.45) with the pulsatility index of CBFV pulses but correlates (p<0.05) with several novel CBFV pulse morphological metrics such as the time interval between the onset of CBFV pulses and ECG QRS peak.

Conclusions

Our results suggest that characterizing CBFV pulse morphology is clinically important because it may offer a potential noninvasive alternative to assess various aspects of ICP such as mean ICP.

Introduction

Current guidelines for management of critically ill stroke patients suggest that treatment in a neurocritical care unit (NCCU) and/or by a neurointensivist (NI) may be beneficial, but the contribution of each to outcome is unknown. The relative impact of a NCCU vs. NI on short- and long-term outcomes in patients with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (SAH) was assessed.

Methods

2,096 stroke patients admitted to a NCCU or non-neuro ICU at a tertiary stroke center were analyzed before the appointment of a NI, during the NI’s tenure, and after the NI departed and was not replaced. Data included admission ICU type, availability of a NI, age, NIHSS, ICH score and 3 and 12 month outcome.

Results

For AIS, compared to the time interval with a NI, departure of the NI predicted a worse rate of return to pre-stroke function at 3 months. For ICH, NCCU treatment predicted shorter ICU and hospital LOS but had no effect on short or long term outcomes. No effect of a NI was seen. For SAH, availability of an NI (but not an NCCU) predicted improved outcomes but longer ICU LOS. Disposition and in-hospital mortality improved when a NI was present, but continued improvement did not occur after the NI’s departure.

Conclusion

Presence of an NI was associated with improved clinical outcomes. This effect was more evident in patients with SAH. Patients with ICH tend to have poor outcomes regardless of the presence of a NCCU or a NI.

Background

Electroencephalographic (EEG) features may provide objective data regarding prognosis in children resuscitated from cardiac arrest (CA), but therapeutic hypothermia (TH) may impact its predictive value. We aimed to determine whether specific EEG features were predictive of short-term outcome in children treated with TH after CA, both during hypothermia and after return to normothermia.

Methods

Thirty-five children managed with a standard clinical TH algorithm after CA were prospectively enrolled. EEG recordings were scored in a standardized manner and categorized. EEG category 1 consisted of continuous and reactive tracings. EEG category 2 consisted of continuous but unreactive tracings. EEG category 3 included those with any degree of discontinuity, burst suppression, or lack of cerebral activity. The primary outcome was unfavorable short-term outcome defined as Pediatric Cerebral Performance Category score of 4–6 (severe disability, vegetative, death) at hospital discharge. Univariate analyses of the association between EEG category and outcome was performed using logistic regression.

Results

For tracings obtained during hypothermia, patients with EEGs in categories 2 or 3 were far more likely to have poor outcome than those in category 1 (OR 10.7, P = 0.023 and OR 35, P = 0.004, respectively). Similarly, for tracings obtained during normothermia, patients with EEGs in categories 2 or 3 were far more likely to have poor outcomes than those in category 1 (OR 27, P = 0.006 and OR 18, P = 0.02, respectively).

Conclusions

A simple EEG classification scheme has predictive value for short-term outcome in children undergoing TH after CA.

Brain injury is the leading cause of death in our pediatric ICU 1. Clinical care for brain injury remains largely supportive. Therapeutic hypothermia has been shown to be effective in improving neurological outcome after adult ventricular-arrhythmia induced cardiac arrest and neonatal asphyxia, and is under investigation as a neuroprotectant after cardiac arrest and traumatic brain injury in children in our ICU and other centers. We routinely induce hypothermia in children comatose after cardiac arrest targeting 32–34°C using cooling blankets and intravenous iced saline as primary methods for induction, for 24–72 hours duration and vigilant re-warming. The objective of this article is to share our hypothermia protocol for cooling children with acute brain injury.

Background

Therapeutic hypothermia is commonly used in comatose survivors’ post-cardiopulmonary resuscitation (CPR). It is unknown whether outcome predictors perform accurately after hypothermia treatment.

Methods

Post-CPR comatose survivors were prospectively enrolled. Six outcome predictors [pupillary and corneal reflexes, motor response to pain, and somatosensory-evoked potentials (SSEP) >72 h; status myoclonus, and serum neuron-specific enolase (NSE) levels <72 h] were systematically recorded. Poor outcome was defined as death or vegetative state at 3 months. Patients were considered “sedated” if they received any sedative drugs ≤12 h prior the 72 h neurological assessment.

Results

Of 85 prospectively enrolled patients, 53 (62%) underwent hypothermia. Furthermore, 53 of the 85 patients (62%) had a poor outcome. Baseline characteristics did not differ between the hypothermia and normothermia groups. Sedative drugs at 72 h were used in 62 (73%) patients overall, and more frequently in hypothermia than in normothermia patients: 83 versus 60% (P = 0.02). Status myoclonus <72 h, absent cortical responses by SSEPs >72 h, and absent pupillary reflexes >72 h predicted poor outcome with a 100% specificity both in hypothermia and normothermia patients. In contrast, absent corneal reflexes >72 h, motor response extensor or absent >72 h, and peak NSE >33 ng/ml <72 h predicted poor outcome with 100% specificity only in non-sedated patients, irrespective of prior treatment with hypothermia.

Conclusions

Sedative medications are commonly used in proximity of the 72-h neurological examination in comatose CPR survivors and are an important prognostication confounder. Patients treated with hypothermia are more likely to receive sedation than those who are not treated with hypothermia.

Background

Recent reports suggest that when thrombolytic agents are administered within the clot, lysis rate accelerates at the expense of increased risk of worsening edema. To test this hypothesis, we report on the volumetric analysis of (1) the intraparenchymal hematoma and, (2) perihematomal edema in a cohort of ICH patients treated with intraclot rtPA.

Methods

A convenience sample of highly selected ICH patients underwent frameless stereotactic aspiration and thrombolysis (FAST) of the clot. Two milligrams of rtPA were administered every 12 h until ICH volume ≤10 cc, or catheter fenestrations were no longer in continuity with the clot. ICH and perihematomal edema volumes were calculated from CT scans. Using random effects linear regression we estimated the rate of hematoma and edema volume resolution as well as their relationship during the first 8 days of lytic therapy.

Results

Fifteen patients were treated, mean age: 60.7 years, median time from ictus to FAST: 1 (range 0–3) day. Using a random effects model that considered volume resolution over the first 8 days following lytic therapy we found that the both percentage hematoma and percentage perihematoma edema resolution per day were quadratic with respect to time. Percentage residual hematoma volume on day K = 97.7% − [24.36%*K] + [1.89%*K2]; P < 0.001 for both terms. Percentage residual edema on day K = 97.4% − [13.94%*K] + [1.30%*K2]; P < 0.001 for K and P = 0.01 for K2. Examination of each patient’s volume data suggests that there exists a strong direct relationship between perihematoma edema volume and same day hematoma volume.

Conclusions

In this cohort of ICH patients treated using FAST, volumetric analysis of ICH and perihematomal edema seems to suggest that local use of rtPA does not exacerbate brain edema formation. Furthermore, there seems to be a strong association between reduction in ICH volume and reduction in edema volume, as would be expected following the concept of “hemotoxicity” postulated by some investigators.

Background

Myocardial injury after aneurysmal subarachnoid hemorrhage (aSAH) is associated with poor outcomes. Delayed cerebral ischemia (DCI) is also a complication of aSAH. We sought to determine whether (1) DCI could be predicted by demographics, aSAH severity/aneurysm location, or aSAH-associated myocardial injury (SAHMI), and (2) DCI is associated with increased mortality after aSAH.

Methods

Prospective longitudinal study of 149 aSAH subjects with definitive DCI evaluation, age 18–75 years, Hunt and Hess (HH) ≥ 3, and/or Fisher ≥ 2, and admitted to the Neurovascular ICU. DCI was defined by the presence of neurological deterioration accompanied by evidence of abnormal cerebral blood flow.

Results

Subjects were 48% DCI(+) and 52% DCI(−). DCI(+) subjects had more severe aSAH [HH (P = 0.002), Fisher (P = 0.004), admission Glasgow Coma Scale (P = 0.018)]. More DCI(+) subjects had pulmonary congestion than DCI(−) subjects (63 vs. 39%, P = 0.003). On echocardiogram, cardiac output (CO, liters per minute [LPM]) was significantly higher in DCI(+) than in DCI(−) subjects (6 ± 2 vs. 5 ± 1 LPM; P = 0.015). Multivariate analysis identified CO and Fisher grade as independent predictors of DCI (P = 0.02, 0.019). For each 1 LPM increase in CO, the odds of DCI increased by 1.5 (95% CI: 1.1–2.1). Fisher grade 4 increased the odds of DCI by 6.5 compared to Fisher grade 2 (95% CI: 1.6–25.8). After controlling for Fisher grade, CO remained an independent predictor of DCI (P = 0.02). Three-month mortality rate was not significantly different between DCI groups, P = 0.786.

Conclusion

Elevated CO and Fisher grade are predictors of DCI after aSAH. However, prevention of DCI may not decrease mortality.

Background

To describe the concept, implementation, patient characteristics, and preliminary outcomes of a Neonatal Neurocritical Care Service (NNCS) recently established at the University of California, San Francisco.

Methods

The NNCS was developed to better address the special needs of neonates at risk for neurological injury. The service combines dedicated neurological care, specialized neonatal medical and nursing expertise, neuromonitoring, neuroimaging, neurodevelopmental care, and long-term follow up. Newborns evaluated by the NNCS between July 2008 and June 2009 were included in the analysis. Demographic data (gestational age at birth, sex, admission diagnosis, and reason for consult), outcome (mortality, length of stay), and neurophysiology and imaging resources were extracted from patient charts.

Results

Over the 12-month period, 155 newborns were evaluated (approximately 25% of all admissions); of these, 51 were preterm (<36 weeks gestation) and 104 were term. Approximately half were admitted for primary medical diagnoses, such as preterm birth, congenital malformations or apnea/apparent life-threatening event (ALTE), with the remainder admitted for primary neurological problems, including perinatal asphyxia, seizures/possible seizures, or congenital cerebral malformation. The most common neurological diagnoses were hypoxic-ischemic encephalopathy (38%) and seizure (35%). Among preterm newborns, intra ventricular hemorrhage grade III and periventricular hemorrhagic infarction were most common. Mortality was approximately 20% in both preterm and term populations.

Conclusions

While specialized neurocritical care has improved outcomes in adult populations, longitudinal studies are needed to determine whether specialized neurocritical care services will also result in improved neurodevelopmental outcomes for newborns.

Background

This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.

Methods

Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.

Results

rCBFDCS and rCBFXeCT showed good correlation (rs = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.

Conclusions

DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.

Background

Cerebral vasospasm is a significant cause of morbidity in patients after aneurysmal subarachnoid hemorrhage (aSAH). There are few effective treatments. The search for new treatments has focused predominantly on dilating cerebral blood vessels. Growing evidence supports a role for inflammation in its pathogenesis but no potential target for intervention has emerged.

Methods

CSF and clinical information from patients with aSAH were collected. Additionally, tyrosine modifications by stable isotope dilution HPLC with online tandem mass spectrometry were quantified in CSF samples.

Results

We report an association between neutrophil accumulation in the cerebrospinal fluid of patients with aSAH and the development of vasospasm. In particular, CSF neutrophil content of >62% on the third day after aSAH is an independent predictor of the later development of vasospasm (OR 6.8, 95% CI 2.0–23.3, P = 0.002). Further, activity of myeloperoxidase and NADPH oxidase is elevated in aSAH suggesting a role for modification of CSF proteins by reactive oxidant species.

Conclusions

Neutrophil percentage is an independent predictor of vasospasm in aSAH patients, days prior to its onset suggesting a role of neutrophils in vasospasm. The activity of neutrophil enzymes is also increased suggesting a mechanism for blood vessel damage. Inflammation mediated by neutrophils is a potential target for therapies in vasospasm. More study is necessary to determine the mechanism by which neutrophils damage cerebral blood vessels.

Introduction

Outcome prediction of patients who are in a locked-in state is challenging. Extensive pontine infarction on diffusion weighted imaging MRI (DWI) has been proposed as a poor prognosticator. We report on three patients with a locked-in state with unexpected favorable recoveries despite DWI evidence of widespread pontine ischemia.

Methods

Report of three cases.

Results

Three young patients (32, 30 and 16 years old) presented with a locked-in state caused by pontine infarction. The first patient did not receive any acute stroke therapies, the second patient underwent endovascular therapy 20 hours after symptom onset resulting in partial recanalization of the basilar artery, and the third patient progressed to a locked-in state despite having received intravenous tissue plasminogen activator. The DWI of all three patients demonstrated acute and widespread pontine infarction involving more than two-thirds of the pons. Two patients regained full independence in their activities of daily living. The third patient remained wheelchair bound, but lives with her family, eats independently, uses a typewriter and wrote a book.

Conclusion

Patients who are in a locked-in state may have substantial functional recovery despite DWI evidence of extensive pontine infarction.

Aneurysmal subarachnoid hemorrhage (SAH) is associated with numerous “delayed neurological deficits” (DNDs) that have been attributed to multiple pathophysiological mechanisms, including ischemia, microthrombosis, free radical damage, inflammation, and vascular remodeling. To date, effective prophylactic therapy for SAH-induced DNDs has been elusive, due perhaps to the multiplicity of mechanisms involved that render typical, single-agent therapy seemingly futile. We hypothesized that heparin, which has multiple underappreciated salutary effects, might be useful as a multitargeted prophylactic agent against SAH-induced DNDs. We performed a comprehensive review of the literature to evaluate the potential utility of heparin in targeting the multiple pathophysiological mechanisms that have been identified as contributing to SAH-induced DNDs. Our literature review revealed that unfractionated heparin can potentially antagonize essentially all of the pathophysiological mechanisms known to be activated following SAH. Heparin binds >100 proteins, including plasma proteins, proteins released from platelets, cytokines, and chemokines. Also, heparin complexes with oxyhemoglobin, blocks the activity of free radicals including reactive oxygen species, antagonizes endothelin-mediated vasoconstriction, smooth muscle depolarization, and inflammatory, growth and fibrogenic responses. Our review suggests that the use of prophylactic heparin following SAH may warrant formal study.

Background

Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability.

Methods

Based on a clinical vignette describing a comatose patient suffering from post-anoxic brain injury intensivists were asked in a semi-structured interview about the patient’s specific neurological prognosis and about prognostication in general. Qualitative research methods were used to identify areas of variability in prognostication and to classify physicians according to specific prognostication profiles. Quantitative statistics were used to assess for associations between prognostication profiles and physicians’ demographic and practice characteristics.

Results

Eighteen intensivists participated. Functional outcome predictions varied along an evaluative dimension (fair/good–poor) and a confidence dimension (certain–uncertain). More experienced physicians tended to be more pessimistic about the patient’s functional outcome and more certain of their prognosis. Attitudes toward quality of life varied along an evaluative dimension (good–poor) and a “style” dimension (objective–subjective). Older and more experienced physicians were more likely to express objective judgments of quality of life and to predict a worse quality of life for the patient than their younger and less experienced counterparts.

Conclusions

Various prognostication profiles exist among intensivists. These may be dictated by factors such as physicians’ age and clinical experience. Awareness of these associations may be a first step to more uniform prognostication.

Background and purpose

Animals subjected to an inflammatory insult with lipopolysaccharide (LPS) at the time of stroke are predisposed to develop a detrimental autoimmune response to myelin basic protein (MBP). In this study, we sought to determine whether other inflammatory stimuli could similarly invoke central nervous system (CNS) autoimmunity and whether these detrimental autoimmune responses occurred to antigens other than MBP.

Methods

Male Lewis rats underwent 3 h middle cerebral artery occlusion (MCAO) and received intraperitoneal injections of LPS, staphylococcal enterotoxin B (SEB), lipoteichoic acid (LTA) or saline at the time of reperfusion. Behavioral tests were performed at set time intervals after MCAO and animals were sacrificed at 1 month to analyze the immune response to MBP, neuron specific enolase (NSE) and proteolipid protein (PLP).

Results

Lymphocytes from SEB treated animals were highly reactive to all tested CNS antigens, but treatment with LPS was most likely to lead to a Th1(+) response. A Th1(+) response to MBP, NSE or PLP in spleen was associated with worse outcome, although the response to NSE was most predictive of poor outcome. Animals with a cell mediated autoimmune response to either MBP or NSE in spleen had a concomitant humoral response to these antigens.

Conclusions

These data show that LPS, but not other inflammatory stimuli, increase the likelihood of developing a detrimental autoimmune response to an array of brain antigens.

Background

Continuous EEG monitoring (cEEG) of critically ill patients is frequently utilized to detect non-convulsive seizures (NCS) and status epilepticus (NCSE). The indications for cEEG, as well as when and how to treat NCS, remain unclear. We aimed to describe the current practice of cEEG in critically ill patients to define areas of uncertainty that could aid in designing future research.

Methods

We conducted an international survey of neurologists focused on cEEG utilization and NCS management.

Results

Three-hundred and thirty physicians completed the survey. 83% use cEEG at least once per month and 86% manage NCS at least five times per year. The use of cEEG in patients with altered mental status was common (69%), with higher use if the patient had a prior convulsion (89%) or abnormal eye movements (85%). Most respondents would continue cEEG for 24 h. If NCS or NCSE is identified, the most common anticonvulsants administered were phenytoin/fosphenytoin, lorazepam, or levetiracetam, with slightly more use of levetiracetam for NCS than NCSE.

Conclusions

Continuous EEG monitoring (cEEG) is commonly employed in critically ill patients to detect NCS and NCSE. However, there is substantial variability in current practice related to cEEG indications and duration and to management of NCS and NCSE. The fact that such variability exists in the management of this common clinical problem suggests that further prospective study is needed. Multiple points of uncertainty are identified that require investigation.

Background

Hematoma volume is a major determinant of outcome in patients with intracerebral hemorrhage (ICH). Accurate volume measurements are critical for predicting outcome and are thought to be more difficult in patients with oral anticoagulation-related ICH (OAT-ICH) due to a higher frequency of irregular shape. We examined hematoma shape and methods of volume assessment in patients with OAT-ICH.

Methods

We performed a case–control analysis of a prospectively identified cohort of consecutive patients with ICH. We retrospectively reviewed 50 consecutive patients with OAT-ICH and 50 location-matched non-OAT-ICH controls. Two independent readers analyzed CT scans for hematoma shape and volume using both ABC/2 and ABC/3 methods. Readers were blinded to all clinical variables including warfarin status. Gold-standard ICH volumes were determined using validated computer-assisted planimetry.

Results

Within this cohort, median INR in patients with OAT-ICH was 3.2. Initial ICH volume was not significantly different between non-OAT-ICH and OAT-ICH (35 ± 38 cc vs. 53 ± 56 cc, P = 0.4). ICH shape did not differ by anticoagulation status (round shape in 10% of OAT-ICH vs. 16% of non-OAT-ICH, P = 0.5). The ABC/3 calculation underestimated median volume by 9 (3–28) cc, while the ABC/2 calculation did so by 4 (0.8–12) cc.

Conclusions

Hematoma shape was not statistically significantly different in patients with OAT-ICH. Among bedside approaches, the standard ABC/2 method offers reasonable approximation of hematoma volume in OAT-ICH and non-OAT-ICH.

Background

The assumption is often made that aggressive care in the form of early decompressive hemicraniectomy is appropriate for young patients who suffer a massive stroke. However, neither their attitude toward aggressive treatment, nor their perception of acceptable quality of life after a stroke, has been adequately studied.

Methods

We conducted a cross-sectional questionnaire-based survey that consisted of demographic information and attitude toward neurological disability based on the highest acceptable modified Rankin Scale (mRS) that they would be “willing to live with.” Young adults in the Los Angeles County were surveyed and grouped by whether or not they would want early decompressive hemicraniectomy after a massive stroke. Logistic regression analysis was used to determine the factors associated with willingness to accept decompressive hemicraniectomy.

Results

Sixty-eight community-dwelling young adults (mean age: 24 ± 6 years) were surveyed. The highest acceptable mRS (0–5) participants felt “willing to live with” were: 10.3% (0), 29.4% (1), 27.9% (2), 20.6% (3), 8.8% (4), 2.9% (5). Despite being presented with a hypothetical high likelihood of long-term disability, 46 of 68 (68%) reported they would undergo hemicraniectomy. Neither the demographic factors nor the highest acceptable mRS was associated with the willingness to seek decompressive hemicraniectomy.

Conclusion

Our study supports the commonly held assumption that the majority of young adults would favor early decompressive hemicraniectomy after a massive ischemic stroke. We also show that a substantial minority in this age group is reluctant to accept this aggressive measure, emphasizing the importance of discussing the individual’s previously stated wishes, even in the young population.