Faculty Bibliography

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.

BACKGROUND: Interhospital transfer of patients with intracranial hemorrhage can offer improved care, but may be associated with complications. METHODS: A prospective single-center study was conducted between 2/2008 and 6/2010 of patients with subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) and subdural hemorrhage (SDH), admitted to the neuro-ICU at a tertiary-care academic hospital. Admission demographics, complications and 3-month functional outcomes were compared between directly admitted and transferred patients. The effect of transfer time on complications and outcomes was assessed. RESULTS: Of 257 total patients, 120 (47%) were transferred and 137 (53%) were directly admitted. About 86 (34%) had SAH, 80 (31%) had ICH and 91 (35%) had SDH. The median transfer time was 190 min (46-1,446). Transferred patients were significantly less educated, less likely to be insured and more frequently had SAH as a diagnosis than directly admitted patients (all P < 0.05), though admission neurological and cognitive status was similar. Complications did not differ between transferred and directly admitted patients; however, among transferred patients, longer transfer time was associated with aneurysm rebleed (7.3 vs. 1.8%, P = 0.007) and tracheostomy (20 vs. 17.5%, P = 0.013). In multivariate analysis, after adjusting for other predictors, transferred patients had worse cognitive outcome at 3-months (adjusted OR 12.4, 95% CI 1.2-125.2, P = 0.033) compared to direct admits, though there were no differences in death, disability or length of stay (LOS). CONCLUSIONS: Transferred patients had similar rates of death, disability and LOS as directly admitted patients, though worse 3-month cognitive outcomes. Prolonged time to interhospital transfer was associated with an increased risk of aneurysm rerupture and tracheostomy.

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.

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.

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.

OBJECTIVES: the frequency and predictors of recurrent symptomatic and angiographic vasospasm after angioplasty or intra-arterial chemical vasodilatation (IACV) in patients with subarachnoid hemorrhage (SAH) are not well characterized. METHODS: a retrospective review of serial clinical and angiographic data was conducted between 7/2001-6/2008 on spontaneous SAH patients who underwent endovascular therapy for symptomatic vasospasm. RESULTS: of 318 SAH patients, symptomatic vasospasm occurred in 80 (25%) and endovascular intervention was performed on 69 (22%) patients. Of these 69 patients, all received IACV in 274 vessels and 33 also underwent angioplasty in a total of 76 vessels. Recurrent angiographic vasospasm occurred in the same vessel segment in 9/23 (39%) patients who received both angioplasty + IACV compared to 40/49 (82%) of patients who received IACV alone (P < 0.001). Recurrent symptomatic vasospasm occurred in 10/26 (38%) angioplasty + IACV patients compared to 28/37 (76%) patients who received IACV alone (P = 0.003). The modified-Fisher Score, A1 spasm, distal and multi-vessel vasospasm predicted recurrent angiographic spasm after IACV alone (P < 0.05). Procedural complications occurred in 4% of IACV alone patients and 6% of angioplasty + IACV patients (P = 0.599). CONCLUSIONS: recurrent angiographic or symptomatic vasospasm is not uncommon after angioplasty + IACV, but appears to occur significantly less than after IACV alone, without any increase in procedural complications.