Coronavirus Disease (COVID-19)-Related Disseminated Leukoencephalopathy: A Retrospective Study of Findings on Brain MRI.

Among 2820 inpatients with coronavirus disease (COVID-19), 59 (2.1%) underwent brain MRI. Of them, six (10.2%) had MRI findings suspicious for COVID-19-related disseminated leukoencephalopathy (CRDL), which is characterized by extensive confluent or multifocal white matter lesions (with characteristics and locations atypical for other causes), microhemorrhages, diffusion restriction, and enhancement. CRDL is an uncommon but important differential consideration in patients with neurologic manifestations of COVID-19.

Serial Neurologic Assessment in Pediatrics (SNAP): A New Tool for Bedside Neurologic Assessment of Critically Ill Children.

OBJECTIVES: We developed a tool, Serial Neurologic Assessment in Pediatrics, to screen for neurologic changes in patients, including those who are intubated, are sedated, and/or have developmental disabilities. Our aims were to: 1) determine protocol adherence when performing Serial Neurologic Assessment in Pediatrics, 2) determine the interrater reliability between nurses, and 3) assess the feasibility and acceptability of using Serial Neurologic Assessment in Pediatrics compared with the Glasgow Coma Scale. DESIGN: Mixed-methods, observational cohort. SETTING: Pediatric and neonatal ICUs. SUBJECTS: Critical care nurses and patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial Neurologic Assessment in Pediatrics assesses Mental Status, Cranial Nerves, Communication, and Motor Function, with scales for children less than 6 months, greater than or equal to 6 months to less than 2 years, and greater than or equal to 2 years old. We assessed protocol adherence with standardized observations. We assessed the interrater reliability of independent Serial Neurologic Assessment in Pediatrics assessments between pairs of trained nurses by percent- and bias- adjusted kappa and percent agreement. Semistructured interviews with nurses evaluated acceptability and feasibility after nurses used Serial Neurologic Assessment in Pediatrics concurrently with Glasgow Coma Scale during routine care. Ninety-eight percent of nurses (43/44) had 100% protocol adherence on the standardized checklist. Forty-three nurses performed 387 paired Serial Neurologic Assessment in Pediatrics assessments (149 < 6 mo; 91 ≥ 6 mo to < 2 yr, and 147 ≥ 2 yr) on 299 patients. Interrater reliability was substantial to near-perfect across all components for each age-based Serial Neurologic Assessment in Pediatrics scale. Percent agreement was independent of developmental disabilities for all Serial Neurologic Assessment in Pediatrics components except Mental Status and lower extremity Motor Function for patients deemed "Able to Participate" with the assessment. Nurses reported that they felt Serial Neurologic Assessment in Pediatrics, compared with Glasgow Coma Scale, was easier to use and clearer in describing the neurologic status of patients who were intubated, were sedated, and/or had developmental disabilities. About 92% of nurses preferred to use Serial Neurologic Assessment in Pediatrics over Glasgow Coma Scale. CONCLUSIONS: When used by critical care nurses, Serial Neurologic Assessment in Pediatrics has excellent protocol adherence, substantial to near-perfect interrater reliability, and is feasible to implement. Further work will determine the sensitivity and specificity for detecting clinically meaningful neurologic decline.

Elevated Red Cell Distribution Width is Associated with Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this retrospective single-center cohort of aSAH patients (October 2009-September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death. RESULTS: Of 179 patients, 27 % had a high Hunt-Hess grade (IV-V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07-6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30-7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt-Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04-629], p = 0.040). CONCLUSIONS: RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

Concussion and football: a review and editorial.

The issue of concussion in football is of substantial interest to players, coaches, fans, and physicians. In this article, we review specific cultural hindrances to diagnosis and treatment of concussion in football. We review current trends in management and identify areas for improvement. We also discuss the obligations that physicians, particularly neurosurgeons and neurologists, have toward brain-injured football players and the larger societal role they may play in helping to minimize football-associated brain injury.

Fever and therapeutic normothermia in severe brain injury: an update.

PURPOSE OF REVIEW: Fever is common in the ICU among patients with severe brain injury. Fever has been consistently shown to exacerbate brain injuries in animal models and has been consistently associated with poor outcome in human studies. However, whether fever control improves outcome and the ideal means of fever control remain unknown. This review will address recent literature on the impact of fever on severe brain injury and on interventions to maintain normothermia. RECENT FINDINGS: Current guidelines generally recommend maintenance of normothermia after brain injury but have scant recommendations on methods to do this. Observational trials have continued to demonstrate the association between fever and poor outcome after severe brain injury. Recent trials have shown the efficacy of more aggressive approaches to fever reduction, whereas a large randomized trial showed the relative ineffectiveness of acetaminophen alone for fever control. Several studies have also described the impact of fever and of fever control on brain physiology. SUMMARY: The value of therapeutic normothermia in the neurocritical care unit (NCCU) is increasingly accepted, yet prospective trials that demonstrate a functional benefit to patients are lacking.

Continuous optical monitoring of cerebral hemodynamics during head-of-bed manipulation in brain-injured adults.

INTRODUCTION: Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering. METHODS: Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30° and then at 0°. Relative CBF (rCBF) and concurrent changes in oxy- (ΔHbO2), deoxy- (ΔHb), and total-hemoglobin concentrations (ΔTHC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed. RESULTS: rCBF, ΔHbO2, and ΔTHC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 ± 28.2 %, P = 0.938). rCBF increased in controls (18.6 ± 9.4 %, P < 0.001). ΔHbO2, ΔHb, and ΔTHC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure. CONCLUSION: DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts.

Response of brain oxygen to therapy correlates with long-term outcome after subarachnoid hemorrhage.

BACKGROUND: Brain oxygen (PbtO2) monitoring can help guide care of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients. The relationship between PbtO2-directed therapy and long-term outcome is unclear. We hypothesized that responsiveness to PbtO2-directed interventions is associated with outcome. METHODS: Seventy-six aSAH patients who underwent PbtO2 monitoring were included. Long-term outcome [Glasgow Outcome Score-Extended (GOS-E) and modified Rankin Scale (mRS)] was ascertained using the social security death database and structured telephone interviews. Univariate and multivariate regression were used to identify variables that correlated with outcome. RESULTS: Data from 64 patients were analyzed (12 were lost to follow-up). There were 530 episodes of compromised PbtO2 (<20 mmHg) during a total of 7,174 h of monitor time treated with 1,052 interventions. Forty-two patients (66 %) survived to discharge. Median follow-up was 8.5 months (range 0.1-87). At most recent follow-up 35 (55 %) patients were alive, and 28 (44 %) had a favorable outcome (mRS ≤3). In multivariate ordinal regression analysis, only age and response to PbtO2-directed intervention correlated significantly with outcome. Increased age was associated with worse outcome (coeff. 0.8, 95 % CI 0.3-1.3, p = 0.003), and response to PbtO2-directed intervention was associated with improved outcome (coeff. -2.12, 95 % CI -4.0 to -0.26, p = 0.03). Patients with favorable outcomes had a 70 % mean rate of response to PbtO2-directed interventions whereas patients with poor outcomes had a 45 % response rate (p = 0.005). CONCLUSIONS: Response to PbtO2-directed intervention is associated with improved long-term functional outcome in aSAH patients.

Stroke and Disseminated Intravascular Coagulation in a Patient With Metastatic Prostate Cancer.

Cancer and stroke comprise two of the most common causes of death worldwide. Despite a significantly increased risk of stroke among patients with cancer, most stroke trials have excluded patients with malignancy. There is thus limited evidence to help guide management decisions in this complex population. We present the case of a 78-year-old man with recurrent strokes - both ischemic and hemorrhagic - in the setting of newly-identified metastatic prostate cancer. An atypical cause of cancer-associated stroke is reviewed and the management is discussed.

Brain lactate metabolism in humans with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. METHODS: Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) <20 mm Hg) versus nonhypoxic and hyperglycolytic (CMD pyruvate >119 µmol/L) versus nonhyperglycolytic. RESULTS: Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). CONCLUSIONS: Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia*.

OBJECTIVE: Early assessment of neurologic recovery is often challenging in survivors of cardiac arrest. Further, little is known about when to assess neurologic status in comatose, postarrest patients receiving therapeutic hypothermia. We sought to evaluate timing of prognostication in cardiac arrest survivors who received therapeutic hypothermia. DESIGN: A retrospective chart review of consecutive postarrest patients receiving therapeutic hypothermia (protocol: 24-hr maintenance at target temperature followed by rewarming over 8 hrs). Data were abstracted from the medical chart, including documentation during the first 96 hrs post arrest of "poor" prognosis, diagnostic tests for neuroprognostication, consultations used for determination of prognosis, and outcome at discharge. SETTING: Two academic urban emergency departments. PATIENTS: A total of 55 consecutive patients who underwent therapeutic hypothermia were reviewed between September 2005 and April 2009. INTERVENTION: None. RESULTS: Of our cohort of comatose postarrest patients, 59% (29 of 49) were male, and the mean age was 56 ± 16 yrs. Chart documentation of "poor" or "grave" prognosis occurred "early": during induction, maintenance of cooling, rewarming, or within 15 hrs after normothermia in 57% (28 of 49) of cases. Of patients with early documentation of poor prognosis, 25% (seven of 28) had care withdrawn within 72 hrs post arrest, and 21% (six of 28) survived to discharge with favorable neurologic recovery. In the first 96 hrs post arrest: 88% (43 of 49) of patients received a head computed tomography, 90% (44 of 49) received electroencephalography, 2% (one of 49) received somatosensory evoked potential testing, and 71% (35 of 49) received neurology consultation. CONCLUSIONS: Documentation of "poor prognosis" occurred during therapeutic hypothermia in more than half of patients in our cohort. Premature documentation of poor prognosis may contribute to early decisions to withdraw care. Future guidelines should address when to best prognosticate in postarrest patients receiving therapeutic hypothermia.

The oculocardiac reflex may mimic signs of intracranial hypertension in patients with combined cerebral and ocular trauma.

BACKGROUND: In the setting of head trauma, progressive bradycardia may raise suspicion for intracranial hypertension, especially when accompanied by pupillary abnormalities or systemic hypertension. METHODS: We describe the case of a patient with concomitant cerebral and ocular trauma who presented with a fixed and dilated pupil and progressive bradycardia due to an oculocardiac reflex. RESULTS: The oculocardiac reflex is an unusual cause of bradycardia due to stimulation of the ophthalmic division of the trigeminal nerve and has been described in a variety of clinical settings. CONCLUSIONS: Clinicians should be aware that the oculocardiac reflex might mimic signs of intracranial hypertension in patients with combined facial and cerebral trauma.

Brain tissue oxygen-based therapy and outcome after severe traumatic brain injury: a systematic literature review.

Observational clinical studies demonstrate that brain hypoxia is associated with poor outcome after severe traumatic brain injury (TBI). In this study, available medical literature was reviewed to examine whether brain tissue oxygen (PbtO2)-based therapy is associated with improved patient outcome after severe TBI. Clinical studies published between 1993 and 2010 that compared PbtO2-based therapy combined with intracranial and cerebral perfusion pressure (ICP/CPP)-based therapy to ICP/CPP-based therapy alone were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. For analysis, each selected paper had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs) of outcome described by the Glasgow outcome score (GOS). Seven studies that compared ICP/CPP and PbtO2- to ICP/CPP-based therapy were identified. There were no randomized studies and no comparison studies in children. Four studies, published in 2003, 2009, and 2010 that included 491 evaluable patients were used in the final analysis. Among patients who received PbtO2-based therapy, 121(38.8%) had unfavorable and 191 (61.2%) had a favorable outcome. Among the patients who received ICP/CPP-based therapy 104 (58.1%) had unfavorable and 75 (41.9%) had a favorable outcome. Overall PbtO2-based therapy was associated with favorable outcome (OR 2.1; 95% CI 1.4-3.1). Summary results suggest that combined ICP/CPP- and PbtO2-based therapy is associated with better outcome after severe TBI than ICP/CPP-based therapy alone. Cross-organizational practice variances cannot be controlled for in this type of review and so we cannot answer whether PbtO2-based therapy improves outcome. However, the potentially large incremental value of PbtO2-based therapy provides justification for a randomized clinical trial.

Obesity is associated with reduced brain tissue oxygen tension after severe brain injury.

BACKGROUND: Obesity has been associated with compromised tissue oxygenation and reduced organ perfusion. The brain is critically dependent on oxygen delivery, and reduced brain tissue oxygen tension (P(bt)O(2)) may result in poor outcome after brain injury. We tested the hypothesis that obesity is associated with compromised P(bt)O(2) after severe brain injury. METHODS: Patients with severe brain injury (GCS score ≤ 8) who underwent continuous P(bt)O(2) monitoring were retrospectively identified from a prospective single-center database. Patients, were classified by body mass index (BMI = weight (kg)/m(2)) and were included if they were obese (BMI ≥ 30) or non-obese (BMI = < 30). RESULTS: Sixty-nine patients (mean age 46.4 ± 17.0 years) were included. Mean daily P(bt)O(2) was 25.8 (9.6) mmHg for the 28 obese and 31.8 (12.3) mmHg for the 41 non-obese patients (P = 0.03). Initial P(bt)O(2) and mean daily maximum P(bt)O(2) measurements also were significantly lower in obese patients than in non-obese patients. Univariate predictors of compromised P(bt)O(2) (defined as minutes P(bt)O(2) < 20 mmHg) included elevated BMI (P = 0.02), presence of ARDS (P < 0.01), mean PaO(2) (P < 0.01), maximum FiO(2) (P < 0.01), mean PaO(2):FiO(2) (P < 0.01), and mean CVP (P < 0.01). In multivariable analysis, BMI was significantly associated with compromised P(bt)O(2) (P = 0.02). Sex, age, and mean CVP were also identified as significant predictors of compromised P(bt)O(2); ARDS and PF ratio were not. CONCLUSIONS: In patients with severe brain injury, obesity was found to be an independent predictor of compromised P(bt)O(2). This effect may be mediated through obesity-related pulmonary dysfunction and inadequate compensatory mechanisms.

Lactate-to-pyruvate ratio as a marker of propofol infusion syndrome after subarachnoid hemorrhage.

BACKGROUND: Propofol infusion syndrome (PRIS) is a rare but frequently fatal condition. It is characterized by cardiovascular collapse and metabolic derangement due to propofol exposure. The pathophysiology of PRIS is poorly understood, and its study has previously been limited to animal models and clinical observations. We present the first in vivo brain biochemical data in a patient with PRIS. METHODS: We report the case of a 37-year-old woman with PRIS following aneurysmal subarachnoid hemorrhage who was monitored by cerebral microdialysis (CMD). A CMD catheter was inserted into the brain and provided near real-time monitoring of brain energy-related metabolites, including lactate and pyruvate, during the time period surrounding the diagnosis of PRIS. We recorded propofol exposure, clinical manifestations, and relevant laboratory measurements. RESULTS: CMD revealed a temporal association between propofol exposure and the cerebral lactate-to-pyruvate ratio (LPR). The LPR increased linearly after propofol was restarted following an off period, and the LPR decreased linearly after propofol was discontinued. Serum lactate correlated with clinical worsening after the onset of PRIS, whereas cerebral LPR correlated with propofol exposure. CONCLUSIONS: Cerebral LPR may be a sensitive marker of PRIS. Increases in LPR following propofol exposure should alert clinicians to the possibility of PRIS and might prompt early discontinuation of propofol thereby avoiding fatal complications.

Medical management of compromised brain oxygen in patients with severe traumatic brain injury.

BACKGROUND: Brain tissue oxygen (PbtO(2)) monitoring is used in severe traumatic brain injury (TBI) patients. How brain reduced PbtO(2) should be treated and its response to treatment is not clearly defined. We examined which medical therapies restore normal PbtO(2) in TBI patients. METHODS: Forty-nine (mean age 40 ± 19 years) patients with severe TBI (Glasgow Coma Scale [GCS] ≤ 8) admitted to a University-affiliated, Level I trauma center who had at least one episode of compromised brain oxygen (PbtO(2) <25 mmHg for >10 min), were retrospectively identified from a prospective observational cohort study. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO(2) were monitored continuously. Episodes of compromised PbtO(2) and brain hypoxia (PbtO(2) <15 mmHg for >10 min) and the medical interventions that improved PbtO(2) were identified. RESULTS: Five hundred and sixty-four episodes of compromised PbtO2 were identified from 260 days of PbtO2 monitoring. Medical management used in a "cause-directed" manner successfully reversed 72% of the episodes of compromised PbtO(2), defined as restoration of a "normal" PbtO(2) (i.e. ≥ 25 mmHg). Ventilator manipulation, CPP augmentation, and sedation were the most frequent interventions. Increasing FiO(2) restored PbtO(2) 80% of the time. CPP augmentation and sedation were effective in 73 and 66% of episodes of compromised brain oxygen, respectively. ICP reduction using mannitol was effective in 73% of treated episodes, though was used only when PbtO(2) was compromised in the setting of elevated ICP. Successful medical treatment of brain hypoxia was associated with decreased mortality. Survivors (n = 38) had a 71% rate of response to treatment and non-survivors (n = 11) had a 44% rate of response (P = 0.01). CONCLUSION: Reduced PbtO(2) may occur in TBI patients despite efforts to maintain CPP. Medical interventions other than those to treat ICP and CPP can improve PbtO(2). This may increase the number of therapies for severe TBI in the ICU.

EEG monitoring during therapeutic hypothermia in neonates, children, and adults.

Therapeutic hypothermia is being utilized as a neuroprotective strategy in neonates, children, and adults. The most common indications are hypoxic ischemic encephalopathy in neonates and post cardiac arrest in adults. Electroencephalographic monitoring use is increasing in critical care units, and is sometimes a component of therapeutic hypothermia clinical pathways. Monitoring may detect non-convulsive seizures or non-convulsive status epilepticus, and it may provide prognostic information. We review data regarding indications for therapeutic hypothermia and electroencephalographic monitoring in neonatal, pediatric, and adult critical care units, and discuss technical aspects related to such monitoring.

A Full-Stack Application for Detecting Seizures and Reducing Data During Continuous Electroencephalogram Monitoring.

Continuous electroencephalogram monitoring is associated with lower mortality in critically ill patients; however, it is underused due to the resource-intensive nature of manually interpreting prolonged streams of continuous electroencephalogram data. Here, we present a novel real-time, machine learning-based alerting and monitoring system for epilepsy and seizures that dramatically reduces the amount of manual electroencephalogram review. METHODS: We developed a custom data reduction algorithm using a random forest and deployed it within an online cloud-based platform, which streams data and communicates interactively with caregivers via a web interface to display algorithm results. We developed real-time, machine learning-based alerting and monitoring system for epilepsy and seizures on continuous electroencephalogram recordings from 77 patients undergoing routine scalp ICU electroencephalogram monitoring and tested it on an additional 20 patients. RESULTS: We achieved a mean seizure sensitivity of 84% in cross-validation and 85% in testing, as well as a mean specificity of 83% in cross-validation and 86% in testing, corresponding to a high level of data reduction. This study validates a platform for machine learning-assisted continuous electroencephalogram analysis and represents a meaningful step toward improving utility and decreasing cost of continuous electroencephalogram monitoring. We also make our high-quality annotated dataset of 97 ICU continuous electroencephalogram recordings public for others to validate and improve upon our methods.

Emergency management of acute ischemic stroke.

With the advent of new therapeutic options for acute ischemic stroke, expeditious evaluation of patients with suspected stroke has become imperative. Goals of the initial evaluation are to determine the time of symptom onset, severity of the neurologic deficit, and to exclude intracranial hemorrhage and other mimics of acute ischemic stroke. CT and MRI perfusion studies may demonstrate the presence of an ischemic penumbra and aid in identification of patients who may benefit from thrombolysis. Intravenous recombinant tissue plasminogen activator (IV rtPA) remains the gold standard for acute ischemic stroke treatment, and the therapeutic time window recently has been extended to 4.5 h in certain patients. Catheter-based intra-arterial thrombolysis is being used increasingly as "rescue therapy" after IV rtPA and as primary therapy in select patients who are ineligible for intravenous therapy. Trials investigating the efficacy and safety of intra-arterial therapy are ongoing.

Effect of shivering on brain tissue oxygenation during induced normothermia in patients with severe brain injury.

BACKGROUND: We analyzed the impact of shivering on brain tissue oxygenation (PbtO(2)) during induced normothermia in patients with severe brain injury. METHODS: We studied patients with severe brain injury who developed shivering during induced normothermia. Induced normothermia was applied to treat refractory fever (body temperature [BT] > or =38.3 degrees C, refractory to conventional treatment) using a surface cooling device with computerized adjustment of patient BT target to 37 +/- 0.5 degrees C. PbtO(2), intracranial pressure, mean arterial pressure, cerebral perfusion pressure, and BT were monitored continuously. Circulating water temperature of the device system was measured to assess the intensity of cooling. RESULTS: Fifteen patients (10 with severe traumatic brain injury, 5 with aneurysmal subarachnoid hemorrhage) were treated with induced normothermia for an average of 5 +/- 2 days. Shivering caused a significant decrease in PbtO(2) levels both in SAH and TBI patients. Compared to baseline, shivering was associated with an overall reduction of PbtO(2) from 34.1 +/- 7.3 to 24.4 +/- 5.5 mmHg (P < 0.001). A significant correlation was found between the magnitude of shivering-associated decrease of PbtO(2) (DeltaPbtO(2)) and circulating water temperature (R = 0.82, P < 0.001). CONCLUSION: In patients with severe brain injury treated with induced normothermia, shivering was associated with a significant decrease of PbtO(2), which correlated with the intensity of cooling. Monitoring of therapeutic cooling with computerized thermoregulatory systems may help prevent shivering and optimize the management of induced normothermia. The clinical significance of shivering-induced decrease in brain tissue oxygenation remains to be determined.

Successful management of refractory intracranial hypertension from acute hyperammonemic encephalopathy in a woman with ornithine transcarbamylase deficiency.

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is the most common of the urea cycle disorders and results in an accumulation of ammonia and its metabolites. Excess ammonia in the brain is metabolized to glutamine, which increases intracellular osmolarity and contributes to cytotoxic edema. METHODS: We report a case of a woman heterozygous for OTCD who developed acute hyperammonemic encephalopathy and increased intracranial pressure (ICP). RESULTS: Despite hemodialysis, protein restriction, and administration of pharmacologic nitrogen scavengers, she developed progressive cerebral edema and increased ICP that was refractory to maximal medical management. She underwent a bifrontal decompressive craniectomy resulting in resolution of her intracranial hypertension. CONCLUSION: Aggressive multimodality management of the patient coupled with bifrontal decompressive hemicraniectomy was a life-saving measure, offering the patient a reasonable outcome. At 6 month follow-up she had moderate disability on the Glasgow Outcome Score associated with cognitive difficulties.