Faculty Bibliography

PURPOSE OF REVIEW: This article summarizes the most common etiologies and approaches to management of metabolic encephalopathy. RECENT FINDINGS: Metabolic encephalopathy is a frequent occurrence in the intensive care unit setting. Common etiologies include hepatic failure, renal failure, sepsis, electrolyte disarray, and Wernicke encephalopathy. Current treatment paradigms typically focus on supportive care and management of the underlying etiology. Directed therapies that target neurochemical and neurotransmitter pathways that mediate encephalopathy are not currently available and represent an important area for future research. Although commonly thought of as reversible neurologic insults, delirium and encephalopathy have been associated with increased mortality, prolonged length of stay and hospital complications, and worse long-term cognitive and functional outcomes. SUMMARY: Recognition and treatment of encephalopathy is critical to improving outcomes in critically ill patients.

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension. Twenty week old C57BL/6 mice were placed on one of three diets: continuous feeding (control), alternate day chow (Intermittent fed, IF), or IF supplemented with polyphenol antioxidants (PAO) from blueberry, pomegranate, and green tea extracts (IF+PAO). Both IF and IF+PAO groups outlived the control group and the IF+PAO group outlived the IF group (all p<0.001). In the brain, IF induced the expression of inflammatory genes and p38 MAPK phosphorylation, while the addition of PAO reduced brain inflammatory gene expression and p38 MAPK phosphorylation. Our data indicate that while IF overall promotes longevity, some aspects of IF-induced stress may paradoxically lessen this effect. Polyphenol compounds, in turn, may potentiate IF-induced longevity by minimizing specific components of IF-induced cell stress.

Onyx embolization of cerebral arteriovenous malformations (AVM) has become increasingly common. We explored the risk of seizures after Onyx use.A retrospective review was conducted of 20 patients with supratentorial brain arteriovenous malformation (AVM) who received Onyx embolization between 2006 and 2009. Baseline demographics, clinical history, seizure history, AVM characteristics and treatment were compared between those who developed post-onyx seizure and those who did not. MRIs were reviewed for edema following Onyx treatment.Of 20 patients who underwent Onyx embolization, the initial AVM presentation was hemorrhage in 40% (N=8). The median number of embolizations was two (range 1-4) and the median final obliteration amount was 90% (range 50-100%). A history of seizure was present in 50% (N=10) of patients pre-embolization and 12 (60%) patients received seizure medications (treatment or prophylaxis) prior to embolization. Seizur post-Onyx embolization occurred in 45% (N=9). The median time to seizur post-Onyx was seven days (range 0.3-210). Four patients (20%) with seizures post-Onyx had no seizure history. Two of these patients (10%) had no other identifiable cause for seizure other than recent Onyx embolization. Seizures in these two patients occurred within 24 hours of Onyx administration. Among patients with post-Onyx seizures, there was a trend toward larger AVM size (P=0.091) and lower percent obliteration (P=0.062). Peri-AVM edema was present in 75% of MRIs performed within one month of Onyx treatment and may represent a possible etiology for seizures.New onset seizures post-Onyx embolization are not uncommon. Further study of seizure prevention is warranted.

OBJECTIVES: Subdural hematoma is a common type of intracranial hemorrhage, particularly among the elderly, yet, despite the aging U.S. population, little has been published in the last 10 yrs. This study aimed to determine national trends in prevalence, discharge disposition, length of stay, and cost of subdural hematoma over time. DESIGN: Retrospective cohort study. SETTING: Adult patients hospitalized in the United States between 1998 and 2007 identified in the Nationwide Inpatient Sample. PARTICIPANTS: Seven hundred twenty thousand, two hundred ninety-seven adult patients hospitalized in subdural hematoma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Discharge disposition, hospital length of stay, and national cost (adjusted to 2007 dollars) were examined. Hospitalizations for subdural hematoma increased from 59,373 (30 per 100,000 hospitalizations) in 1998 to 91,935 (42 per 100,000) in 2007, constituting a 39% per-capita increase. The prevalence of subdural hematoma increased with age (p < .001), particularly among those >80 yrs of age (36% of subdural hematoma cohort), in lower income patients, in patients with acquired abnormalities of the coagulation cascade, and in patients with trauma. Inhospital mortality decreased from 15% to 12% (p = .001), but unsatisfactory discharge disposition increased from 17% to 20% (p < .001). National cost increased from $1.0 to $1.6 billion (p < .001). Unsatisfactory discharge disposition and cost were both independently predicted by higher comorbidity index, alcohol abuse, history of trauma, and acquired abnormal coagulation or platelet factors (p < .05). Neurosurgical intervention for subdural hematoma decreased from 41% in 1998 to 31% in 2007 (p < .001). Subdural hematoma evacuation was associated with decreased mortality but did not significantly protect against poor discharge disposition and was associated with significantly higher cost. CONCLUSIONS: The prevalence and total cost for subdural hematoma has increased significantly in the last decade nationwide. Health resource consumption for subdural hematoma is increasing without clear evidence that management practices are leading to improved outcomes.

BACKGROUND: Poor clinical condition is the most important predictor of neurological outcome and mortality after subarachnoid hemorrhage (SAH). Rupture of an intracranial aneurysm was shown to be associated with acute ischemic brain injury in poor grade patients in autopsy studies and small magnetic resonance imaging series. METHODS: We performed diffusion-weighted magnetic resonance imaging (DWI) within 96 h of onset in 21 SAH patients with Hunt-Hess grade 4 or 5 enrolled in the Columbia University SAH Outcomes Project between July 2004 and February 2007. We analyzed demographic, radiological, clinical data, and 3 months outcome. RESULTS: Of the 21 patients 13 were Hunt-Hess grade 5, and eight were grade 4. Eighteen patients (86%) displayed bilateral and symmetric abnormalities on DWI, but not on computed tomography (CT). Involved regions included both anterior cerebral artery territories (16 patients), and less often the thalamus and basal ganglia (4 patients), middle (6 patients) or posterior cerebral artery territories (2 patients), or cerebellum (2 patients). At 1-year, 15 patients were dead (life support had been withdrawn in 6), 2 were moderately to severely disabled (modified Rankin Scale [mRS] = 4-5), and 4 had moderate-to-no disability (mRS = 1-3). CONCLUSIONS: Admission DWI demonstrates multifocal areas of acute ischemic injury in poor grade SAH patients. These ischemic lesions may be related to transient intracranial circulatory arrest, acute vasoconstriction, microcirculatory disturbances, or decreased cerebral perfusion from neurogenic cardiac dysfunction. Ischemic brain injury in poor grade SAH may be a feasible target for acute resuscitation strategies.

Delirium is defined by a fluctuating level of attentiveness and has been associated with increased ICU mortality and poor cognitive outcomes in both general ICU and neurocritical care populations. Sedation use in the ICU can contribute to delirium. Limiting ICU sedation allows for the diagnosis of underlying acute neurological insults associated with delirium and leads to shorter mechanical ventilation time, shorter length of stay, and improved 1 year mortality rates. Identifying the underlying etiology of delirium is critical to developing treatment paradigms.

BACKGROUND: Little current data exists regarding outcome, cost, and length of stay (LOS) after subdural hemorrhage (SDH). We sought to examine predictors of discharge disposition, ICU and hospital LOS and direct, indirect, ICU, surgical, and diagnostic costs for SDH. METHODS: A retrospective review was conducted of 216 SDH patients, aged >18 years admitted to our hospital between 1/2001 and 12/2008. Discharge disposition was characterized as dead, poor or good. Multivariable logistic regression analysis was performed to identify predictors of disposition, LOS, and cost. RESULTS: Of 216 SDH patients, the median age was 74 (19-95), and the median admission Glasgow Coma Scale (GCS) was 14 (3-15). The SDH was characterized as acute in 14%, subacute in 44%, chronic in 12%, and mixed in 30%. Surgical evacuation was performed in 139 (64%) patients. Death occurred in 29 (13%) patients and poor disposition in 43 (20%). Significant predictors of death included age, admission GCS, and hospital LOS (P < 0.05). Longer hospital LOS was associated with poor disposition, while shorter ICU LOS was associated with good disposition (P < 0.01). Median hospital LOS was 8 (1-99) days. Median total direct costs for hospitalization were $10,670 ($907-238,856). ICU and hospital LOS were significant predictors of all measures of cost (P < 0.05). SDH size, chronicity, and surgical intervention were not predictors of any outcome. There was no significant change in any outcome variable between 2001 and 2008. CONCLUSIONS: Despite good admission neurological status, death or poor discharge disposition is common after SDH. LOS and costs remain high and have not improved in the last decade.

Acute liver failure (ALF) is uncommon in the United States, but presents acutely and catastrophically, often with deadly consequences. Hepatic encephalopathy, cerebral edema, elevated intracranial pressure, and intracranial hemorrhage due to coagulopathy are common occurrences in patients with ALF. Appropriate management of multi-system organ failure and neurological complications are essential in bridging patients to transplant and ensuring satisfactory outcomes.