Safety, Efficacy, and Clinical Outcomes of Dexmedetomidine for Sedation in Traumatic Brain Injury: A Scoping Review.

Dexmedetomidine is a promising alternative sedative agent for moderate-severe Traumatic brain injury (TBI) patients. Although the data are limited, the posited benefits of dexmedetomidine in this population are a reduction in secondary brain injury compared with current standard sedative regimens. In this scoping review, we critically appraised the literature to examine the effects of dexmedetomidine in patients with moderate-severe TBI to examine the safety, efficacy, and cerebral and systemic physiological outcomes within this population. We sought to identify gaps in the literature and generate directions for future research. Two researchers and a librarian queried PubMed, Embase, Scopus, and APA PsycINFO databases. Of 920 studies imported for screening, 11 were identified for inclusion in the review. The primary outcomes in the included studied were cerebral physiology, systemic hemodynamics, sedation levels and delirium, and the presence of paroxysmal sympathetic hyperactivity. Dexmedetomidine dosing ranged from 0.2 to 1 ug/kg/h, with 3 studies using initial boluses of 0.8 to 1.0 ug/kg over 10 minutes. Dexmedetomidine used independently or as an adjunct seems to exhibit a similar hemodynamic safety profile compared with standard sedation regimens, albeit with transient episodes of bradycardia and hypotension, decrease episodes of agitation and may serve to alleviate symptoms of sympathetic hyperactivity. This scoping review suggests that dexmedetomidine is a safe and efficacious sedation strategy in patients with TBI. Given its rapid onset of action and anxiolytic properties, dexmedetomidine may serve as a feasible sedative for TBI patients.

The joint impacts of sex and race/ethnicity on incidence of grade 1 versus grades 2-3 meningioma across the lifespan.

Background: Previous research has identified older age, African-American race, and female sex as meningioma risk factors, but there is limited information on their joint effects, or on how these demographic factors vary across strata of tumor grade. Methods: The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry combining data from the CDC's National Program of Cancer Registries and NCI's Surveillance, Epidemiology and End Results Program which covers ~100% of the U.S. population and aggregates incidence data on all primary malignant and nonmalignant brain tumors. These data were used to explore the joint impacts of sex and race/ethnicity on average annual age-adjusted incidence rates of meningioma. We calculated meningioma incidence rate ratios (IRRs) by sex and race/ethnicity, across strata of age and tumor grade. Results: Compared to individuals who are non-Hispanic White, individuals who are non-Hispanic Black had significantly higher risk of grade 1 (IRR = 1.23; 95% CI: 1.21-1.24) and grade 2-3 meningioma (IRR = 1.42; 95% CI: 1.37-1.47). The female-to-male IRR peaked in the fifth decade of life across all racial/ethnic groups and tumor grades, but was 3.59 (95% CI: 3.51-3.67) for WHO grade 1 meningioma and 1.74 (95% CI: 1.63-1.87) for WHO grade 2-3 meningioma. Conclusions: This study reveals the joint effects of sex and race/ethnicity on meningioma incidence throughout the lifespan and across strata of tumor grade, highlighting incidence disparities among females and African-Americans that may inform future strategies for tumor interception.

Association of Brain Injury Biomarkers and Circulatory Shock Following Moderate-Severe Traumatic Brain Injury: A TRACK-TBI Study.

INTRODUCTION: Early circulatory shock following traumatic brain injury (TBI) is a multifactorial process; however, the impact of brain injury biomarkers on the risk of shock has not been evaluated. We examined the association between neuronal injury biomarker levels and the development of circulatory shock following moderate-severe TBI. METHODS: In this retrospective cohort study, we examined adults with moderate-severe TBI (Glasgow Coma Scale score <13) enrolled in the TRACK-TBI study, an 18-center prospective TBI cohort study. The exposures were day-1 levels of neuronal injury biomarkers (glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1 [UCH-L1], S100 calcium-binding protein B [S100B], neuron-specific enolase), and of an inflammatory biomarker (high-sensitivity C-reactive protein). The primary outcome was the development of circulatory shock, defined as cardiovascular Sequential Organ Failure Assessment Score ≥2 within 72 hours of admission. Association between day-1 biomarker levels and the development of circulatory shock was assessed with regression analysis. RESULTS: The study included 392 subjects, with a mean age of 40 years; 314 (80%) were male and 165 (42%) developed circulatory shock. Median (interquartile range) day-1 levels of UCH-L1 (994.8 [518.7 to 1988.2] pg/mL vs. 548.1 [280.2 to 1151.9] pg/mL; P <0.0001) and S100B (0.47 µg/mL [0.25 to 0.88] vs. 0.27 [0.16 to 0.46] µg/mL; P <0.0001) were elevated in those who developed early circulatory shock compared with those who did not. In multivariable regression, there were associations between levels of both UCH-L1 (odds ratio, 1.63 [95% confidence interval, 1.25-2.12]; P <0.0005) and S100B (odds ratio, 1.73 [95% confidence interval 1.27-2.36]; P <0.0005) with the development of circulatory shock. CONCLUSION: Neuronal injury biomarkers may provide the improved mechanistic understanding and possibly early identification of patients at risk for early circulatory shock following moderate-severe TBI.

Utilization and Outcomes of Extracorporeal Membrane Oxygenation Following Traumatic Brain Injury in the United States.

Objectives: Describe contemporary ECMO utilization patterns among patients with traumatic brain injury (TBI) and examine clinical outcomes among TBI patients requiring ECMO. Design: Retrospective cohort study. Setting: Premier Healthcare Database (PHD) between January 2016 to June 2020. Subjects: Adult patients with TBI who were mechanically ventilated and stratified by exposure to ECMO. Results: Among patients exposed to ECMO, we examined the following clinical outcomes: hospital LOS, ICU LOS, duration of mechanical ventilation, and hospital mortality. Of our initial cohort (n = 59,612), 118 patients (0.2%) were placed on ECMO during hospitalization. Most patients were placed on ECMO within the first 2 days of admission (54.3%). Factors associated with ECMO utilization included younger age (OR 0.96, 95% CI (0.95-0.97)), higher injury severity score (ISS) (OR 1.03, 95% CI (1.01-1.04)), vasopressor utilization (2.92, 95% CI (1.90-4.48)), tranexamic acid utilization (OR 1.84, 95% CI (1.12-3.04)), baseline comorbidities (OR 1.06, 95% CI (1.03-1.09)), and care in a teaching hospital (OR 3.04, 95% CI 1.31-7.05). A moderate degree (ICC = 19.5%) of variation in ECMO use was explained at the individual hospital level. Patients exposed to ECMO had longer median (IQR) hospital and ICU length of stay (LOS) [26 days (11-36) versus 9 days (4-8) and 19.5 days (8-32) versus 5 days (2-11), respectively] and a longer median (IQR) duration of mechanical ventilation [18 days (8-31) versus 3 days (2-8)]. Patients exposed to ECMO experienced a hospital mortality rate of 33.9%, compared to 21.2% of TBI patients unexposed to ECMO. Conclusions: ECMO utilization in mechanically ventilated patients with TBI is rare, with significant variation across hospitals. The impact of ECMO on healthcare utilization and hospital mortality following TBI is comparable to non-TBI conditions requiring ECMO. Further research is necessary to better understand the role of ECMO following TBI and identify patients who may benefit from this therapy.

Palliative Care Consultations in Patients with Severe Traumatic Brain Injury: Who Receives Palliative Care Consultations and What Does that Mean for Utilization?

BACKGROUND: Palliative care has the potential to improve goal-concordant care in severe traumatic brain injury (sTBI). Our primary objective was to illuminate the demographic profiles of patients with sTBI who receive palliative care encounters (PCEs), with an emphasis on the role of race. Secondary objectives were to analyze PCE usage over time and compare health care resource utilization between patients with or without PCEs. METHODS: The National Inpatient Sample database was queried for patients age ≥ 18 who had a diagnosis of sTBI, defined by using International Classification of Diseases, 9th Revision codes. PCEs were defined by using International Classification of Diseases, 9th Revision code V66.7 and trended from 2001 to 2015. To assess factors associated with PCE in patients with sTBI, we performed unweighted generalized estimating equations regression. PCE association with decision making was modeled via its effect on rate of percutaneous endoscopic gastrostomy (PEG) tube placement. To quantify differences in PCE-related decisions by race, race was modeled as an effect modifier. RESULTS: From 2001 to 2015, the proportion of palliative care usage in patients with sTBI increased from 1.5 to 36.3%, with 41.6% White, 22.3% Black, and 25% Hispanic patients with sTBI having a palliative care consultation in 2015, respectively. From 2008 to 2015, we identified 17,673 sTBI admissions. White and affluent patients were more likely to have a PCE than Black, Hispanic, and low socioeconomic status patients. Across all races, patients receiving a PCE resulted in a lower rate of PEG tube placement; however, White patients exhibited a larger reduction of PEG tube placement than Black patients. Patients using palliative care had lower total hospital costs (median $16,368 vs. $26,442, respectively). CONCLUSIONS: Palliative care usage for sTBI has increased dramatically this century and it reduces resource utilization. This is true across races, however, its usage rate and associated effect on decision making are race-dependent, with White patients receiving more PCE and being more likely to decline the use of a PEG tube if they have had a PCE.

Utilization of Brain Tissue Oxygenation Monitoring and Association with Mortality Following Severe Traumatic Brain Injury.

BACKGROUND: The aim of this study was to describe the utilization patterns of brain tissue oxygen (PbtO2) monitoring following severe traumatic brain injury (TBI) and determine associations with mortality, health care use, and pulmonary toxicity. METHODS: We conducted a retrospective cohort study of patients from United States trauma centers participating in the American College of Surgeons National Trauma Databank between 2008 and 2016. We examined patients with severe TBI (defined by admission Glasgow Coma Scale score ≤ 8) over the age of 18 years who survived more than 24 h from admission and required intracranial pressure (ICP) monitoring. The primary exposure was PbtO2 monitor placement. The primary outcome was hospital mortality, defined as death during the hospitalization or discharge to hospice. Secondary outcomes were examined to determine the association of PbtO2 monitoring with health care use and pulmonary toxicity and included the following: (1) intensive care unit length of stay, (2) hospital length of stay, and (3) development of acute respiratory distress syndrome (ARDS). Regression analysis was used to assess differences in outcomes between patients exposed to PbtO2 monitor placement and those without exposure by using propensity weighting to address selection bias due to the nonrandom allocation of treatment groups and patient dropout. RESULTS: A total of 35,501 patients underwent placement of an ICP monitor. There were 1,346 (3.8%) patients who also underwent PbtO2 monitor placement, with significant variation regarding calendar year and hospital. Patients who underwent placement of a PbtO2 monitor had a crude in-hospital mortality of 31.1%, compared with 33.5% in patients who only underwent placement of an ICP monitor (adjusted risk ratio 0.84, 95% confidence interval 0.76-0.93). The development of the ARDS was comparable between patients who underwent placement of a PbtO2 monitor and patients who only underwent placement of an ICP monitor (9.2% vs. 9.8%, adjusted risk ratio 0.89, 95% confidence interval 0.73-1.09). CONCLUSIONS: PbtO2 monitor utilization varied widely throughout the study period by calendar year and hospital. PbtO2 monitoring in addition to ICP monitoring, compared with ICP monitoring alone, was associated with a decreased in-hospital mortality, a longer length of stay, and a similar risk of ARDS. These findings provide further guidance for clinicians caring for patients with severe TBI while awaiting completion of further randomized controlled trials.

Epidemiology and Outcomes of Acute Respiratory Distress Syndrome Following Isolated Severe Traumatic Brain Injury.

Patients with traumatic brain injury (TBI) are at risk for extra-cranial complications, such as the acute respiratory distress syndrome (ARDS). We conducted an analysis of risk factors, mortality, and healthcare utilization associated with ARDS following isolated severe TBI. The National Trauma Data Bank (NTDB) dataset files from 2007-2014 were used to identify adult patients who suffered isolated [other body region-specific Abbreviated Injury Scale (AIS) < 3] severe TBI [admission total Glasgow Coma Scale (GCS) from 3 to 8 and head region-specific AIS >3]. In-hospital mortality was compared between patients who developed ARDS and those who did not. Utilization of healthcare resources (ICU length of stay, hospital length of stay, duration of mechanical ventilation, and frequency of tracheostomy and gastrostomy tube placement) was also examined. This retrospective cohort study included 38,213 patients with an overall ARDS occurrence of 7.5%. Younger age, admission tachycardia, pre-existing vascular and respiratory diseases, and pneumonia were associated with the development of ARDS. Compared to patients without ARDS, patients that developed ARDS experienced increased in-hospital mortality (OR 1.13, 95% CI 1.01-1.26), length of stay (p = <0.001), duration of mechanical ventilation (p = < 0.001), and placement of tracheostomy (OR 2.70, 95% CI 2.34-3.13) and gastrostomy (OR 2.42, 95% CI 2.06-2.84). After isolated severe TBI, ARDS is associated with increased mortality and healthcare utilization. Future studies should focus on both prevention and management strategies specific to TBI-associated ARDS.

Multiorgan Dysfunction After Severe Traumatic Brain Injury: Epidemiology, Mechanisms, and Clinical Management.

Traumatic brain injury (TBI) is a major global health problem and a major contributor to morbidity and mortality following multisystem trauma. Extracranial organ dysfunction is common after severe TBI and significantly impacts clinical care and outcomes following injury. Despite this, extracranial organ dysfunction remains an understudied topic compared with organ dysfunction in other critical care paradigms. In this review, we will: 1) summarize the epidemiology of extracranial multiorgan dysfunction following severe TBI; 2) examine relevant mechanisms that may be involved in the development of multi-organ dysfunction following severe TBI; and 3) discuss clinical management strategies to care for these complex patients.

Echocardiogram Utilization Patterns and Association With Mortality Following Severe Traumatic Brain Injury.

BACKGROUND: Severe traumatic brain injury (TBI) can result in left ventricular dysfunction, which can lead to hypotension and secondary brain injuries. Although echocardiography is often used to examine cardiovascular function in multiple clinical settings, its use and association with outcomes following severe TBI are not known. To address this gap, we used the National Trauma Data Bank (NTDB) to describe utilization patterns of echocardiography and examine its association with mortality following severe TBI. METHODS: A retrospective cohort study was conducted using a large administrative trauma registry maintained by the NTDB from 2007 to 2014. Patients >18 years with isolated severe TBI, and without concurrent severe polytrauma, were included in the study. We examined echocardiogram utilization patterns (including overall utilization, factors associated with utilization, and variation in utilization) and the association of echocardiography utilization with hospital mortality, using multivariable logistic regression models. RESULTS: Among 47,808 patients, echocardiogram was utilized as part of clinical care in 2548 patients (5.3%). Clinical factors including vascular comorbidities and hemodynamic instability were associated with increased use of echocardiograms. Nearly half (46.0%, 95% confidence interval [CI], 40.3%-51.7%) of the variation in echocardiogram utilization was explained at the individual hospital level, above and beyond patient and injury factors. Exposure to an echocardiogram was associated with decreased odds of in-hospital mortality following severe TBI (adjusted odds ratio [OR] = 0.77; 95% CI, 0.69-0.87; P < .001). CONCLUSIONS: Echocardiogram utilization following severe TBI is relatively low, with wide variation in use at the hospital level. The association with decreased in-hospital mortality suggests that the information derived from echocardiography may be relevant to improving patient outcomes but will require confirmation in further prospective studies.

Therapeutic Development of Apolipoprotein E Mimetics for Acute Brain Injury: Augmenting Endogenous Responses to Reduce Secondary Injury.

Over the last few decades, increasing evidence demonstrates that the neuroinflammatory response is a double-edged sword. Although overly robust inflammatory responses may exacerbate secondary tissue injury, inflammatory processes are ultimately necessary for recovery. Traditional drug discovery often relies on reductionist approaches to isolate and modulate specific intracellular pathways believed to be involved in disease pathology. However, endogenous brain proteins are often pleiotropic in order to regulate neuroinflammation and recovery mechanisms. Thus, a process of "backward translation" aims to harness the adaptive properties of endogenous proteins to promote earlier and greater recovery after acute brain injury. One such endogenous protein is apolipoprotein E (apoE), the primary apolipoprotein produced in the brain. Robust preclinical and clinical evidence demonstrates that endogenous apoE produced within the brain modulates the neuroinflammatory response of the acutely injured brain. Thus, one innovative approach to improve outcomes following acute brain injury is administration of exogenous apoE-mimetic drugs optimized to cross the blood-brain barrier. In particular, one promising apoE mimetic peptide, CN-105, has demonstrated efficacy across a wide variety of preclinical models of brain injury and safety and feasibility in early-phase clinical trials. Preclinical and clinical evidence for apoE's neuroprotective effects and downregulation of neuroinflammatory and the resulting translational therapeutic development strategy for an apoE-based therapeutic are reviewed.

Masson's tumor presenting as a left frontal intraparenchymal hemorrhage resulting in severe expressive aphasia during pregnancy: case report.

Intravascular papillary endothelial hyperplasia (IPEH), commonly known as Masson's tumor, is a benign lesion that manifests as an excessive proliferation of endothelial cells within a vessel wall. IPEH is extremely rare in the brain, with only 36 intracranial cases previously described in the literature. It is commonly mistaken for more malignant pathologies, such as angiosarcoma. Careful histopathological examination is required for diagnosis, as no clinical or radiographic features are characteristic of this lesion. In this first published case of intracranial IPEH presenting during pregnancy, the authors describe a 32-year-old female with a left frontal intraparenchymal hemorrhage resulting in complete expressive aphasia at 28 weeks 6 days' gestation. An MRI scan obtained at a local hospital demonstrated an area of enhancement within the hemorrhage. The patient underwent a left frontoparietal craniotomy for hematoma evacuation and gross-total resection (GTR) of an underlying hemorrhagic mass at 29 weeks' gestation. This case illustrates the importance of multidisciplinary patient care and the feasibility of intervention in the early third trimester with subsequent term delivery. While GTR of IPEH is typically curative, the decision to proceed with surgical treatment of any intracranial lesion in pregnancy must balance maternal stability, gestational age, and suspected pathology.

Cortical stimulation mapping for localization of visual and auditory language in pediatric epilepsy patients.

OBJECTIVE: To determine resection margins near eloquent tissue, electrical cortical stimulation (ECS) mapping is often used with visual naming tasks. In recent years, auditory naming tasks have been found to provide a more comprehensive map. Differences in modality-specific language sites have been found in adult patients, but there is a paucity of research on ECS language studies in pediatric patients. The goals of this study were to evaluate word-finding distinctions between visual and auditory modalities and identify which cortical subregions most often contain critical language function in a pediatric population. METHODS: Twenty-one pediatric patients with epilepsy or temporal lobe pathology underwent ECS mapping using visual (n = 21) and auditory (n = 14) tasks. Fisher's exact test was used to determine whether the frequency of errors in the stimulated trials was greater than the patient's baseline error rate for each tested modality and subregion. RESULTS: While the medial superior temporal gyrus was a common language site for both visual and auditory language (43.8% and 46.2% of patients, respectively), other subregions showed significant differences between modalities, and there was significant variability between patients. Visual language was more likely to be located in the anterior temporal lobe than was auditory language. The pediatric patients exhibited fewer parietal language sites and a larger range of sites overall than did adult patients in previously published studies. CONCLUSIONS: There was no single area critical for language in more than 50% of patients tested in either modality for which more than 1 patient was tested (n > 1), affirming that language function is plastic in the setting of dominant-hemisphere pathology. The high rates of language function throughout the left frontal, temporal, and anterior parietal regions with few areas of overlap between modalities suggest that ECS mapping with both visual and auditory testing is necessary to obtain a comprehensive language map prior to epileptic focus or tumor resection.

The assassination of Robert F. Kennedy: an analysis of the senator's injuries and neurosurgical care.

On June 5, 1968, having won the Democratic Party presidential primary in California, Senator Robert F. Kennedy delivered a victory speech to supporters at the Ambassador Hotel in downtown Los Angeles. Just after 12:15 am (Pacific daylight savings time), a lone assassin shot Kennedy 3 times at point-blank range. One of the bullets struck Kennedy in the right posterior auricular region. Within the ensuing 26 hours, Kennedy was transported to 2 hospitals, underwent emergency surgery, and eventually died of severe brain injury. Although this story has been repeated in the press and recounted in numerous books, this is the first analysis of the senator's injuries and subsequent surgical care to be reported in the medical literature. The authors review eyewitness reports on the mechanism of injury, the care rendered for 3 hours prior to the emergency craniotomy, the clinical course, and, ultimately, the autopsy.

Masson's tumor of the pineal region: case report.

Intracranial intravascular papillary endothelial hyperplasia (IPEH), also referred to as Masson's tumor, is a condition that rarely occurs in the nervous system. IPEH most frequently occurs extracranially in the skin of the face, skull, neck, and trunk and can easily be mistaken clinically, radiologically, and histologically for angiosarcoma, organizing hematoma, or other vascular malformations. IPEH accounts for roughly 2% of all vascular tumors and is extremely rare intracranially, with only 23 reported cases compared with more than 300 cases of IPEH occurring in the skin and subcutaneous tissue. To date, it has never been reported to occur in the pineal region. The authors report the case of a patient with an IPEH in the pineal region who underwent complex resection and experienced reversal of neurological symptoms.

Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival.

OBJECTIVE: The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. METHODS: A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. RESULTS: A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02-1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95-0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31-0.83]; p = 0.0067) to be significantly associated with survival. CONCLUSION: This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.

Symptomatic Rathke's cleft cyst with a co-existing pituitary tumor; Brief review of the literature.

Pituitary adenomas and Rathke's cleft cysts (RCCs) share a common embryological origin. Occasionally, these two lesions can present within the same patient. We present a case of a 39-year-old male who was found to have a large sellar lesion after complaints of persistent headaches and horizontal nystagmus. Surgical resection revealed components of a RCC co-existing with a pituitary adenoma. A brief review of the literature was performed revealing 38 cases of co-existing Rathke's cleft cysts and pituitary adenomas. Among the cases, the most common symptoms included headache and visual changes. Rathke's cleft cysts and pituitary adenomas are rarely found to co-exist, despite having common embryological origins. We review the existing literature, discuss the common embryology to these two lesions and describe a unique case from our institution of a co-existing Rathke's cleft cyst and pituitary adenoma.

Reorganization and stability for motor and language areas using cortical stimulation: case example and review of the literature.

The cerebral organization of language in epilepsy patients has been studied with invasive procedures such as Wada testing and electrical cortical stimulation mapping and more recently with noninvasive neuroimaging techniques, such as functional MRI. In the setting of a chronic seizure disorder, clinical variables have been shown to contribute to cerebral language reorganization underscoring the need for language lateralization and localization procedures. We present a 14-year-old pediatric patient with a refractory epilepsy disorder who underwent two neurosurgical resections of a left frontal epileptic focus separated by a year. He was mapped extraoperatively through a subdural grid using cortical stimulation to preserve motor and language functions. The clinical history and extensive workup prior to surgery is discussed as well as the opportunity to compare the cortical maps for language, motor, and sensory function before each resection. Reorganization in cortical tongue sensory areas was seen concomitant with a new zone of ictal and interictal activity in the previous tongue sensory area. Detailed neuropsychological data is presented before and after any surgical intervention to hypothesize about the extent of reorganization between epochs. We conclude that intrahemispheric cortical plasticity does occur following frontal lobe resective surgery in a teenager with medically refractory seizures.

RIP-Chip: the isolation and identification of mRNAs, microRNAs and protein components of ribonucleoprotein complexes from cell extracts.

RNA targets of multitargeted RNA-binding proteins (RBPs) can be studied by various methods including mobility shift assays, iterative in vitro selection techniques and computational approaches. These techniques, however, cannot be used to identify the cellular context within which mRNAs associate, nor can they be used to elucidate the dynamic composition of RNAs in ribonucleoprotein (RNP) complexes in response to physiological stimuli. But by combining biochemical and genomics procedures to isolate and identify RNAs associated with RNA-binding proteins, information regarding RNA-protein and RNA-RNA interactions can be examined more directly within a cellular context. Several protocols--including the yeast three-hybrid system and immunoprecipitations that use physical or chemical cross-linking--have been developed to address this issue. Cross-linking procedures in general, however, are limited by inefficiency and sequence biases. The approach outlined here, termed RNP immunoprecipitation-microarray (RIP-Chip), allows the identification of discrete subsets of RNAs associated with multi-targeted RNA-binding proteins and provides information regarding changes in the intracellular composition of mRNPs in response to physical, chemical or developmental inducements of living systems. Thus, RIP-Chip can be used to identify subsets of RNAs that have related functions and are potentially co-regulated, as well as proteins that are associated with them in RNP complexes. Using RIP-Chip, the identification and/or quantification of RNAs in RNP complexes can be accomplished within a few hours or days depending on the RNA detection method used.