Aneurysmal Bone Cyst of the Sphenoid Body Mimicking Craniopharyngioma: A Case Report.

An aneurysmal bone cyst is a locally destructive benign lesion that predominately affects the long bones. Sphenoid body involvement is rare. To date, only 19 primary aneurysmal bone cysts of the sphenoid body have been reported. We describe the case of an 18-year-old male with a one-week history of severe right eye pain and lacrimation, right-sided diplopia, right-sided headache, photophobia, nausea, and vomiting. Magnetic resonance imaging (MRI) demonstrated a lobulated lesion centered in the sphenoid body with expansion into the cavernous sinus, sellar region, and clivus. The lesion had a homogenous hyperintense T2 signal with enhancing sidewalls and minimal septations. Computed tomography (CT) angiography revealed a hypoattenuating lesion containing a substance of nine Hounsfield units, compatible with water density. The clinicoradiologic findings were consistent with a craniopharyngioma. Intraoperatively, the lesion was confirmed to contain clear fluid and have prominent arterial feeding vessels. The extradural tumor was then excised with intralesional curettage. The histopathologic analysis resulted in a diagnosis of an aneurysmal bone cyst. This case highlights the potentially non-specific and variable appearance of aneurysmal bone cysts and the need to consider it in the differential diagnosis of sphenoid bone lesions.

High glucose variability increases cerebral infarction in patients with spontaneous subarachnoid hemorrhage.

PURPOSE: High glucose variability is a significant marker for poor outcome in critically ill patients. We evaluated the impact of high glucose variability on cerebral infarction following spontaneous subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Consecutive adult patients with spontaneous SAH and Hunt Hess score of at least 3 were retrospectively identified. Patients were excluded if their intensive care unit length of stay was less than 24 hours or if there were less than 5 glucose assessments. Glucose values from the first 7 days of intensive care unit admission were assessed. Variability was calculated as the average change in glucose over time for each patient. Classification and regression tree analysis was used to determine high vs low glucose variability, and the incidence of cerebral infarction was compared. Multivariate analysis was used to control for confounding variables. RESULTS: There were 42 patients. Classification and regression tree analysis revealed a change in glucose greater than 9.52 mg/dL/h as the determinant for high variability. The incidence of cerebral infarction was 64% when glucose variability was high vs 20% when it was low (P=.006). Multivariate analysis identified high glucose variability (odds ratio [95% confidence interval]=11.4 [1.9-70.2], P=.008) and female sex (odds ratio [95% confidence interval]=5.2 [1-26.8], P=.047) as independent predictors for cerebral infarction. CONCLUSION: Glucose variability is a significant predictor of cerebral infarction in patients with severe spontaneous SAH.

Goal directed brain tissue oxygen monitoring versus conventional management in traumatic brain injury: an analysis of in hospital recovery.

BACKGROUND: Brain tissue oxygen monitoring (pBtO2) has been advocated in the treatment of patients with severe traumatic brain injuries (TBI); however, controversy exists regarding the improvements that pBtO2 monitoring provides. The objective of our study was to evaluate our experience and effect on mortality with goal directed pBtO2 monitoring for severe TBI compared to traditional ICP/CPP monitoring. METHODS: All patients admitted with severe TBI (GCS < 8) to our Level 1 trauma center from June 2007 through June 2009 were retrospectively analyzed. All patients had ICP monitoring and pBtO2 monitors were placed based on the current practices of the attending neurosurgeon producing two temporally matched cohorts of patients with and without pBtO2 monitors. Exclusion criteria were age <18 years and survival <24 h. Goal-directed therapy was utilized in all patients to maintain ICP <20 mmHg and CPP >60 mmHg. Patients with pBtO2 monitors were managed to maintain a level >20 mmHg. RESULTS: 74 patients were treated for severe TBI over the 2-year study period with 37 patients in each group. Both groups were similar in age, sex, and admission Glascow Coma Score(GCS).The pBtO2-monitored group did, however, have significantly lower injury severity score [26 (25-30) vs. 30 (26-36), p = 0.03] and AIS Chest [0 (0-0) vs. 2 (0-3), p = 0.02]. There was no survival difference found (64.9 vs. 54.1 %, p = 0.34). No difference with respect to discharge GCS or discharge Functional Independence Measure score was identified. CONCLUSIONS: Compared with ICP/CPP-directed therapy alone, the addition of pBtO2 monitoring did not provide a survival or functional status improvement at discharge. The true clinical benefit of pBtO2 monitoring will require further study.

The first 72 hours of brain tissue oxygenation predicts patient survival with traumatic brain injury.

BACKGROUND: Utilization of brain tissue oxygenation (pBtO(2)) is an important but controversial variable in the treatment of traumatic brain injury. We hypothesize that pBtO(2) values over the first 72 hours of monitoring are predictive of mortality. METHODS: Consecutive, adult patients with severe traumatic brain injury and pBtO(2) monitors were retrospectively identified. Time-indexed measurements of pBtO(2), cerebral perfusion pressure (CPP), and intracranial pressure (ICP) were collected, and average values over 4-hour blocks were determined. Patients were stratified according to survival, and repeated measures analysis of variance was used to compare pBtO(2), CPP, and ICP. The pBtO(2) threshold most predictive for survival was determined. RESULTS: There were 8,759 time-indexed data points in 32 patients. The mean age was 39 years ± 16.5 years, injury severity score was 27.7 ± 10.7, and Glasgow Coma Scale score was 6.6 ± 3.4. Survival was 68%. Survivors consistently demonstrated higher pBtO(2) values compared with nonsurvivors including age as a covariate (F = 12.898, p < 0.001). Individual pBtO(2) was higher at the time points 8 hours, 12 hours, 20 hours to 44 hours, 52 hours to 60 hours, and 72 hours of monitoring (p < 0.05). There was no difference in ICP (F = 1.690, p = 0.204) and CPP (F = 0.764, p = 0.389) values between survivors and nonsurvivors including age as a covariate. Classification and regression tree analysis identified 29 mm Hg as the threshold at which pBtO(2) was most predictive for mortality. CONCLUSION: The first 72 hours of pBtO(2) neurologic monitoring predicts mortality. When the pBtO(2) monitor remains below 29 mm Hg in the first 72 hours of monitoring, mortality is increased. This study challenges the brain oxygenation threshold of 20 mm Hg that has been used conventionally and delineates a time for monitoring pBtO(2) that is predictive of outcome. LEVEL OF EVIDENCE: III, prognostic study.

Retrospective evaluation of nicardipine versus labetalol for blood pressure control in aneurysmal subarachnoid hemorrhage.

BACKGROUND: American Heart Association/American Stroke Association guidelines for management of aneurysmal subarachnoid hemorrhage (aSAH) recommend blood pressure (BP) control, utilizing labetalol or nicardipine, but do not differentiate efficacy between the two agents. The purpose of this retrospective study was to compare BP control between labetalol and nicardipine in patients following aSAH. METHODS: Consecutive adult patients admitted to the ICU with a diagnosis of SAH treated with labetalol or nicardipine were retrospectively identified. Patients were included if they received more than one bolus dose of labetalol or a nicardipine infusion for greater than 3 h. Patients were excluded if they were <18 years of age, experiencing an ICH, acute ischemic stroke or a TIA. Patients were stratified into two groups (labetalol vs. nicardipine) and data was collected for 72 h. The outcomes compared were time within goal mean arterial pressure (MAP), average MAP/patient, MAP variability, initial response to therapy, and treatment failure. Goal MAP was defined as 70-110 mmHg. RESULTS: There were 103 patients evaluated (labetalol n = 43; nicardipine n = 60). Demographics and baseline MAP were similar between the two groups. Nicardipine was associated with a longer time within goal MAP (78 ± 24 vs. 58 ± 36 %, p = 0.001) and lower average MAP/patient (93 ± 11 vs. 106 ± 12 mmHg, p < 0.001). There was no difference in MAP variability between the nicardipine and labetalol groups (13 ± 5 mmHg vs. 11 ± 4 mmHg; p = 0.137). Nicardipine led to a more rapid response to therapy (F = 8.1; p = 0.005) and fewer treatment failures (0 vs. 28 %, p < 0.001). CONCLUSIONS: Our study showed nicardipine to be associated with superior BP control versus labetalol in aSAH.

Cerebral perfusion pressure and intracranial pressure are not surrogates for brain tissue oxygenation in traumatic brain injury.

OBJECTIVE: Utilization of brain tissue oxygenation (pBtO(2)) is an important but controversial variable in the treatment of traumatic brain injury (TBI). We evaluated the correlation between pBtO(2)/CPP and pBtO(2)/ICP and determined the parameter most closely related to survival. METHODS: Consecutive, adult patients with severe TBI and pBtO(2) monitors were retrospectively identified. Time-indexed measurements of pBtO(2), CPP and ICP were collected and correlation coefficients were determined. Patients were then stratified according to survival and pBtO(2), CPP and ICP values were compared between groups. RESULTS: There were 4169 time-indexed data points (i.e., pBtO(2) with respective CPP and ICP values) in 15 patients. The cohort consisted of a mean age of 37±17 years, ISS of 27±7 and GCS of 4.5±1.5. Survival was 53% (8/15). In a normal regression models, neither the ICP (p=0.58) nor the CPP (p=0.71) predict pBtO(2) significantly. There was a significant difference in pBtO(2) in survivors (31.5±3.1 vs. 25.2±4.8, p=0.010) but not in CPP or ICP. Survivors had a lower proportion of time with pBtO(2)<25 mmHg [20% (3.4-44.6) vs. 40% (16.2-89), p=0.049]. In contrast, survivors had a greater proportion of time with CPP<70 and no difference in the proportion of time with and ICP>20. CONCLUSIONS: CPP and ICP should not be used as surrogates for pBtO(2) since cerebral oxygenation varies independently of cerebral hemodynamics and pressures. Brain tissue oxygen monitoring in patients with TBI provides unique information regarding cerebral oxygenation the utility of which remains to be fully described. SIGNIFICANCE: CPP and ICP are not surrogates for pBtO(2). Brain tissue oxygenation monitoring provides unique information for the treatment of traumatically injured patients.

Methazolamide and melatonin inhibit mitochondrial cytochrome C release and are neuroprotective in experimental models of ischemic injury.

BACKGROUND AND PURPOSE: The identification of a neuroprotective drug for stroke remains elusive. Given that mitochondria play a key role both in maintaining cellular energetic homeostasis and in triggering the activation of cell death pathways, we evaluated the efficacy of newly identified inhibitors of cytochrome c release in hypoxia/ischemia induced cell death. We demonstrate that methazolamide and melatonin are protective in cellular and in vivo models of neuronal hypoxia. METHODS: The effects of methazolamide and melatonin were tested in oxygen/glucose deprivation-induced death of primary cerebrocortical neurons. Mitochondrial membrane potential, release of apoptogenic mitochondrial factors, pro-IL-1beta processing, and activation of caspase -1 and -3 were evaluated. Methazolamide and melatonin were also studied in a middle cerebral artery occlusion mouse model. Infarct volume, neurological function, and biochemical events were examined in the absence or presence of the 2 drugs. RESULTS: Methazolamide and melatonin inhibit oxygen/glucose deprivation-induced cell death, loss of mitochondrial membrane potential, release of mitochondrial factors, pro-IL-1beta processing, and activation of caspase-1 and -3 in primary cerebrocortical neurons. Furthermore, they decrease infarct size and improve neurological scores after middle cerebral artery occlusion in mice. CONCLUSIONS: We demonstrate that methazolamide and melatonin are neuroprotective against cerebral ischemia and provide evidence of the effectiveness of a mitochondrial-based drug screen in identifying neuroprotective drugs. Given the proven human safety of melatonin and methazolamide, and their ability to cross the blood-brain-barrier, these drugs are attractive as potential novel therapies for ischemic injury.

Differential susceptibility to excitotoxic stress in YAC128 mouse models of Huntington disease between initiation and progression of disease.

Huntington disease (HD) is a neurodegenerative disorder caused by an expanded CAG tract in the HD gene. Polyglutamine expansion of huntingtin (htt) results in early, progressive loss of medium spiny striatal neurons, as well as cortical neurons that project to the striatum. Excitotoxicity has been postulated to play a key role in the selective vulnerability of striatal neurons in HD. Early excitotoxic neuropathological changes observed in human HD brain include increased quinolinate (QUIN) concurrent with proliferative changes such as increased spine density and dendritic length. In later stages of the disease, degenerative-type changes are apparent, such as loss of dendritic arborization, a reduction in spine density and reduced levels of 3-hydroxykynurenine and QUIN. It is currently unknown whether sensitivity to excitotoxic stress varies between initiation and progression of disease. Here, we have assessed the excitotoxic phenotype in the YAC128 mouse model of HD by examining the response to excitotoxic stress at different stages of disease. Our results demonstrate that YAC128 mice display enhanced sensitivity to NMDA ex vivo and QUIN in vivo before obvious phenotypic changes. In contrast, 10-month-old symptomatic YAC128 mice are resistant to QUIN-induced neurotoxicity. These findings are paralleled by a significant increase in NMDAR-mediated membrane currents in presymptomatic YAC128 dissociated medium spiny neurons progressing to reduced NMDAR-mediated membrane currents with disease progression. These data highlight the dynamic nature of the mutant htt-mediated excitotoxic phenotype and suggests that therapeutic approaches to HD may need to be altered, depending on the stage and development of the disease.

Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 activation in Huntington's disease.

Caspase-1 plays a role in the pathogenesis of a variety of neurological diseases. Caspase-1 activation is an early event in models of Huntington's disease (HD). However, mechanisms regulating the activation of this apical caspase in cell death are not known. Receptor interacting protein-2 (Rip2) and caspase recruitment domain (CARD) only protein (Cop) are two CARD proteins with significant homology to the caspase-1 CARD and modulate caspase-1 activation in inflammation. Rip2 is a caspase-1 activator, and Cop is a caspase-1 inhibitor. We demonstrate in models of HD that caspase-1 activation results from dysregulation of caspase-1 activation pathways. Associated with disease progression, we detect elevation of the caspase-1 activator Rip2 and reduction of the caspase-1 inhibitor Cop. Knocking down endogenous Rip2/Cop respectively results in reduced/increased sensitivity to neurotoxic stimuli. Our data provide evidence that caspase-1-mediated cell death is regulated, at least in part, by the balance of Rip2 and Cop, and alterations of this balance may contribute to aberrant caspase-1-mediated pathogenesis in Huntington's disease.

Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice.

Creatine mediates remarkable neuroprotection in experimental models of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and traumatic brain injury. Because caspase-mediated pathways are shared functional mechanistic components in these diseases, as well as in ischemia, we evaluated the effect of creatine supplementation on an experimental stroke model. Oral creatine administration resulted in a remarkable reduction in ischemic brain infarction and neuroprotection after cerebral ischemia in mice. Postischemic caspase-3 activation and cytochrome c release were significantly reduced in creatine-treated mice. Creatine administration buffered ischemia-mediated cerebral ATP depletion. These data provide the first direct correlation between the preservation of bioenergetic cellular status and the inhibition of activation of caspase cell-death pathways in vivo. An alternative explanation to our findings is that creatine is neuroprotective through other mechanisms that are independent of mitochondrial cell-death pathways, and therefore postischemic ATP preservation is the result of tissue sparing. Given its safety record, creatine might be considered as a novel therapeutic agent for inhibition of ischemic brain injury in humans. Prophylactic creatine supplementation, similar to what is recommended for an agent such as aspirin, may be considered for patients in high stroke-risk categories.