Augmented expression of TSPO after intracerebral hemorrhage: a role in inflammation?

BACKGROUND: Intracerebral hemorrhage (ICH) is a potentially fatal stroke subtype accounting for 10-15 % of all strokes. Despite neurosurgical intervention and supportive care, the 30-day mortality rate remains 30-50 % with ICH survivors frequently displaying neurological impairment and requiring long-term assisted care. Although accumulating evidence demonstrates the role of neuroinflammation in secondary brain injury and delayed fatality after ICH, the molecular regulators of neuroinflammation remain poorly defined after ICH. METHODS: In the present study, ICH was induced in CD1 male mice by collagenase injection method and given the emerging role of TSPO (18-kDa translocator protein) in neuroinflammation, immunofluorescence staining of brain sections was performed to characterize the temporal expression pattern and cellular and subcellular localization of TSPO after ICH. Further, both genetic and pharmacological studies were employed to assess the functional role of TSPO in neuroinflammation. RESULTS: The expression of TSPO was found to be increased in the peri-hematomal brain region 1 to 7 days post-injury, peaking on day 3 to day 5 in comparison to sham. Further, the TSPO expression was mostly observed in microglia/macrophages, the inflammatory cells of the central nervous system, suggesting an unexplored role of TSPO in neuroinflammatory responses after ICH. Further, the subcellular localization studies revealed prominent perinuclear expression of TSPO after ICH. Moreover, both genetic and pharmacological studies revealed a regulatory role of TSPO in the release of pro-inflammatory cytokines in a macrophage cell line, RAW 264.7. CONCLUSIONS: Altogether, the data suggest that TSPO induction after ICH could be an intrinsic mechanism to prevent an exacerbated inflammatory response and raise the possibility of targeting TSPO for the attenuation of secondary brain injury after ICH.

Overexpression of Nrf2 attenuates Carmustine-induced cytotoxicity in U87MG human glioma cells.

BACKGROUND: Malignant glioma is one of the most devastating tumors in adults with poor patient prognosis. Notably, glioma often exhibits resistance to conventional chemotherapeutic approaches, complicating patient treatments. However, the molecular mediators involved in tumor chemoresistance remain poorly defined, creating a barrier to the successful management of glioma. In the present study, we hypothesized that the antioxidant transcription factor, Nrf2 (nuclear factor erythroid-derived 2 like 2), attenuates glioma cytotoxicity to Carmustine (BCNU), a widely used chemotherapeutic agent known to modulate cellular oxidative balance. METHODS: To test the hypothesis, we employed human malignant glioma cell line, U87MG and overexpression of Nrf2 in glioma cells was achieved using both pharmacological and genetic approaches. RESULTS: Notably, induction of Nrf2 was associated with increased expression of heme oxygenase-1 (HO-1), a stress inducible enzyme involved in anti-oxidant defense. In addition, over expression of Nrf2 in U87MG cells significantly attenuated the cytotoxicity of Carmustine as evidenced by both cellular viability assay and flow cytometry analysis. Consistent with this, antioxidants such as glutathione and N-acetyl cysteine significantly reduced Carmustine mediated glioma cytotoxicity. CONCLUSIONS: Taken together, these data strongly implicate an unexplored role of Nrf2 in glioma resistance to Carmustine and raise the possible use of Nrf2 inhibitors as adjunct to Carmustine for the treatment of malignant glioma.

Cavernous malformations of the central nervous system: An international consensus statement.

Introduction: Cavernous malformations (CM) of the central nervous system constitute rare vascular lesions. They are usually asymptomatic, which has allowed their management to become quite debatable. Even when they become symptomatic their optimal mode and timing of treatment remains controversial. Research question: A consensus may navigate neurosurgeons through the decision-making process of selecting the optimal treatment for asymptomatic and symptomatic CMs. Material and methods: A 17-item questionnaire was developed to address controversial issues in relation to aspects of the treatment, surgical planning, optimal surgical strategy for specific age groups, the role of stereotactic radiosurgery, as well as a follow-up pattern. Consequently, a three-stage Delphi process was ran through 19 invited experts with the goal of reaching a consensus. The agreement rate for reaching a consensus was set at 70%. Results: A consensus for surgical intervention was reached on the importance of the patient's age, symptomatology, and hemorrhagic recurrence; and the CM's location and size. The employment of advanced MRI techniques is considered of value for surgical planning. Observation for asymptomatic eloquent or deep-seated CMs represents the commonest practice among our panel. Surgical resection is considered when a deep-seated CM becomes symptomatic or after a second bleeding episode. Asymptomatic, image-proven hemorrhages constituted no indication for surgical resection for our panelists. Consensus was also reached on not resecting any developmental venous anomalies, and on resecting the associated hemosiderin rim only in epilepsy cases. Discussion and conclusion: Our Delphi consensus provides an expert common practice for specific controversial issues of CM patient management.

Age-dependent lethality in novel transgenic mouse models of central nervous system arteriovenous malformations.

BACKGROUND AND PURPOSE: The lack of an appropriate animal model has been a limitation in studying hemorrhage from arteriovenous malformations (AVMs) in the central nervous system. METHODS: Novel mouse central nervous system AVM models were generated by conditionally deleting the activin receptor-like kinase (Alk1; Acvrl1) gene with the SM22-Cre transgene. All mice developed AVMs in their brain and/or spinal cord, and >80% of them showed a paralysis or lethality phenotype due to internal hemorrhages during the first 10 to 15 weeks of life. The mice that survived this early lethal period, however, showed significantly reduced lethality rates even though they carried multiple AVMs. RESULTS: The age-dependent change in hemorrhage rates allowed us to identify molecular factors uniquely upregulated in the rupture-prone AVM lesions. CONCLUSIONS: Upregulation of angiopoietin 2 and a few inflammatory genes were identified in the hemorrhage-prone lesions, which may be comparable with human pathology. These models will be an exceptional tool to study pathophysiology of AVM hemorrhage.

Critical Appraisal of Randomized Controlled Trials on Unruptured Brain Arteriovenous Malformations.

OBJECTIVE: Brain arteriovenous malformations management remains controversial despite the numerous, available treatment options. Randomized controlled trials (RCTs) theoretically provide the strongest evidence for the assessment of any therapeutic intervention. However, poorly designed RCTs may be associated with biases, inaccuracies, and misleading conclusions. The purpose of our study is to assess reporting transparency and methodological quality of the existing RCTs. METHODS: A search was performed in the PubMed, Scopus, Embase, clinicaltrials.gov, and Cochrane databases. The search was limited to English literature. We included all published RCTs reporting on the management of unruptured brain arteriovenous malformations. The eligible studies were evaluated by 5 blinded raters with the CONsolidated Standards of Reporting Trials 2010 statement and the risk-of-bias 2 tool. The inter-rater agreement was assessed with the Fleiss' Kappa. RESULTS: A randomized trial of unruptured brain arteriovenous malformations (ARUBA) and treatment of brain arteriovenous malformations (TOBAS) trials were evaluated. ARUBA achieved high CONsolidated standards of reporting trials compliance, while TOBAS showed a moderate one. In ARUBA the introduction, discussion, and other information sections reached the highest compliance rate (80%-86%). The lowest rates were recorded in the results and the methods (62% and 73%, respectively). The inter-rater agreement was moderate to substantial (54.1% to 78.4%). All the examined studies demonstrated a high risk of bias, mainly related to ill-defined intended interventions, missing outcome data, and selection of the reported results. CONCLUSIONS: Our study confirmed the high risk of bias mainly attributed to several protocol violations, deviations, minimal external validity and selection, attrition, and allocation biases of the ARUBA trial. Analysis of the TOBAS trial revealed a moderate overall reporting clarity and a high risk of bias.

Astrocyte-derived glutathione attenuates hemin-induced apoptosis in cerebral microvascular cells.

Intracerebral hemorrhage (ICH) induces neurovascular injury via poorly defined mechanisms. The aim of this study was to determine whether gliovascular communication may restrict hemorrhagic vascular injury. Hemin, a hemoglobin by-product, concentration- and time-dependently increased apoptotic cell death in mouse bEnd.3 cells and in primary human brain microvascular endothelial cells, at least in part, via a caspase-3 dependent pathway. Cell death was preceded by a NFκB-mediated increase in inflammatory gene expression, including upregulation of inducible nitric oxide synthase (iNOS) expression and activity. Functionally, inhibition of iNOS or the addition of a peroxynitrite decomposition catalyst reduced cell death. Interestingly, co-treatment with astrocyte-conditioned media (ACM) reversed hemin-induced NFκB activation, nitrotyrosine formation, and apoptotic cell death, at least in part, via the release of the endogenous antioxidant, reduced glutathione (GSH). Prior treatment of astrocytes with the GSH-depleting agent, DL-buthionine (S,R)-sulfoximine or direct addition of diethyl maleate, a thiol-depleting agent, to ACM reversed the observed protection. In contrast, neither exogenous GSH nor the GSH precursor, N-acetylcysteine, was protective in bEnd.3 cells. Together, these data support an important role for astrocyte-derived GSH in the maintenance of oxidative balance in the vasculature and suggest therapeutic targeting of the GSH system may reduce neurological injury following ICH.

Elucidating novel mechanisms of brain injury following subarachnoid hemorrhage: an emerging role for neuroproteomics.

Subarachnoid hemorrhage (SAH) is a devastating neurological injury associated with significant patient morbidity and death. Since the first demonstration of cerebral vasospasm nearly 60 years ago, the preponderance of research has focused on strategies to limit arterial narrowing and delayed cerebral ischemia following SAH. However, recent clinical and preclinical data indicate a functional dissociation between cerebral vasospasm and neurological outcome, signaling the need for a paradigm shift in the study of brain injury following SAH. Early brain injury may contribute to poor outcome and early death following SAH. However, elucidation of the complex cellular mechanisms underlying early brain injury remains a major challenge. The advent of modern neuroproteomics has rapidly advanced scientific discovery by allowing proteome-wide screening in an objective, nonbiased manner, providing novel mechanisms of brain physiology and injury. In the context of neurosurgery, proteomic analysis of patient-derived CSF will permit the identification of biomarkers and/or novel drug targets that may not be intuitively linked with any particular disease. In the present report, the authors discuss the utility of neuroproteomics with a focus on the roles for this technology in understanding SAH. The authors also provide data from our laboratory that identifies high-mobility group box protein-1 as a potential biomarker of neurological outcome following SAH in humans.

A simple and cost-effective model for ventricular catheter placement training: technical note.

OBJECTIVE: External ventricular drain (EVD) placement is one of first cranial procedures neurosurgery residents are expected to perform independently. While proper training improves patient outcomes, there are few options for practicing EVD placement prior to placing the EVD in patients in a clinical setting. Proposed solutions to this include using cadaveric models and virtual simulations, but barriers exist with these as well in regard to authenticity. EVD simulators using virtual reality technologies are a promising new technique for training, but the cost of these devices poses a barrier to general/widespread accessibility among smaller programs or underserved hospitals. The authors desribe a novel, yet simple, and cost-effective technique (less than $5 per mold) for developing a brain model constructed of homemade ballistics gelatin that can be used for teaching and practicing the placement of EVD. METHODS: A brain model is made with ballistics gelatin using an anatomically correct skull model as a mold. A 3D-printed ventricular system model is used to create a mold of an anatomically correct ventricular system in the brain model. A group of medical students (n = 10) were given a basic presentation about EVD placement, including standard landmarks and placement techniques, and were also shown a demonstration of EVD placement on the brain model. They were then allowed to perform an EVD placement using the brain model. The students were surveyed on their experience with using the brain model, including usability and practicality of the model. Accuracy of EVD placement by each student was also assessed, with adequate position of catheter tip being in the ipsilateral frontal horn. RESULTS: The final product is fairly inexpensive and easy to make. It is soft enough to pass a catheter through, but it is also firm enough to maintain its shape, including a cavity representing the lateral ventricles. The dense gelatin holds the catheter in its final resting position, while the two halves are separated and inspected. All participants in the test group of medical students reported that the brain model was easy to use, helped them understand the steps and technique of EVD placement, and provided good feedback on the ideal position of ventricular catheters. All of the participants in the group had adequate positioning of their ventricular catheters after one attempt. CONCLUSIONS: The presented brain model is easy to replicate, inexpensive, anatomically accurate, and provides a medium for neurosurgeons to teach and practice ventricular catheter placement in a risk-free environment.

Arteriovenous Malformations: Congenital or Acquired Lesions?

OBJECTIVE: Arteriovenous malformations (AVMs) were believed to be congenital. However, an increasing number of de novo AVM cases have questioned this doctrine. METHODS: A consensus meeting of international experts attempted to establish a consensus on the nature of these relatively rare but challenging vascular lesions. In addition, an extensive search of the subject was performed using the PubMed medical database. RESULTS: All participants agreed that genetic factors may play a role in the pathogenesis of AVMs. All but 1 participant believed that an underlying genetic predisposition may be detected later on in a patient's life, whereas genetic variations may contribute to sporadic AVM formation. The presence of genetic variations alone may not be enough for an AVM formation. A second hit is probably required. This consensus opinion is also supported by our literature search. CONCLUSIONS: We discuss the literature on the genetics of AVMs and compare it with the consensus meeting outcomes. The congenital or noncongenital character of intracranial AVMs has an impact on the understanding their biological behavior, as well as their efficient short-term and long-term management.

Sellar/Suprasellar Ganglioglioma: Clinical Image.

BACKGROUND: This report presents a rare presentation of a ganglioglioma in the sellar/suprasellar region. On the basis of the patient's presentation and imaging characteristics, the initial diagnosis was craniopharyngioma. While gangliogliomas are already rare brain tumors that are usually found in the frontal and temporal lobes of young patients, the presentation of this tumor in the sellar region is exceedingly rare. CASE DESCRIPTION: A 25-year-old male presented to the emergency department with headache, agitation, and combativeness. A head computed tomography scan showed a sellar/suprasellar mass with mixed solid and cystic components and peripheral calcifications. The mass compressed the third ventricle and cerebral aqueduct, resulting in obstructive hydrocephalus. The patient was intubated for decline in mental status and combativeness. A ventricular drain was placed emergently. A pituitary function panel did not show endocrine dysfunction. Magnetic resonance imaging showed a 3.6 cm × 4.2 cm solid mass in the sellar/suprasellar region with a cystic component. The mass displaced the adenohypophysis and extended into the prepontine and interpedicular cisterns. The clinical presentation and radiologic characteristics led to an initial diagnosis of craniopharyngioma. The patient underwent a right pterional craniotomy and transsylvian approach for resection of mass without complication, although a subtotal resection was achieved due to adherence of the tumor to optic nerves and carotid arteries. The resected specimen was diagnosed as ganglioglioma. CONCLUSIONS: This case is a reminder of how much the field of neurosurgery relies on imaging modalities but also emphasizes the importance of histopathology in the field of brain tumors.

A Retrospective Cohort Analysis of Hemorrhagic Arteriovenous Malformations Treated with Combined Endovascular Embolization and Gamma Knife Stereotactic Radiosurgery.

BACKGROUND: The management of brain arteriovenous malformations (AVMs) remains a controversial topic. Given the relatively low incidence, high heterogeneity, and high morbidity and mortality of these lesions, consensus on treatment strategies is an issue of concern to organized neurosurgery. The present retrospective analysis examined and quantified the outcomes of patients with an initial presentation of intracranial hemorrhage from a Spetzler-Martin grade III or IV AVM, later ruled out as surgical candidates. METHODS: A total of 16 patients (5 females; 11 males) had presented with symptomatic hemorrhage confirmed by non-contrast-enhanced computed tomography and were deemed to not be surgical candidates owing to AVM location and/or architecture. The patients underwent combined endovascular embolization and gamma knife stereotactic radiosurgery (SRS). The modified Rankin scale was used to measure the clinical outcomes, comparing the scores at presentation, gamma knife treatment, and the last known follow-up examination. A radiographic evaluation was used to determine the level of AVM nidus involution after the procedure. RESULTS: The present study identified 16 patients with ruptured high-grade AVMs of high surgical risk. All the patients had undergone immediate embolization with delayed SRS for treatment of the hemorrhage and nidus of the AVM. A statistically significant proportion of patients showed marked improvement in the modified Rankin scale scores. No subsequent repeat hemorrhage or any associated complications after embolization occurred in any patient. CONCLUSION: These findings warrant consideration of endovascular embolization with adjuvant SRS as a powerful treatment option for cases with high surgical morbidity due to AVM characteristics.

Hemin-induced necroptosis involves glutathione depletion in mouse astrocytes.

Intracerebral hemorrhage (ICH) is a devastating neurological injury associated with significant mortality. Astrocytic inflammation may contribute to the pathogenesis of ICH, although the underlying cellular mechanisms remain unclear. In this study, the hemoglobin oxidation by-product, hemin, concentration dependently induced necroptotic cell death in cortical astrocytes within 5 h of treatment. Hemin-induced cell death was preceded by increased inflammatory gene expression (COX-2, IL-1beta, TNF-alpha, iNOS). Inhibition of the NF-kappaB transcription factor reversed inflammatory gene expression and attenuated cell death after hemin treatment, suggesting a possible role for inflammatory mediators in astrocytic injury. Superoxide production paralleled the increase in iNOS expression, and inhibition of either iNOS (aminoguanidine or iminopiperdine) or superoxide (apocynin) significantly reduced cell death. Similarly, reduced formation of peroxynitrite, the damaging product of nitric oxide and superoxide, significantly reduced hemin injury. Hemin-induced peroxidative injury was associated with a rapid depletion of intracellular glutathione (GSH), culminating in lipid peroxidation and cell death, effects that were reduced by cotreatment with exogenous GSH, N-acetyl-L-cysteine, or the glutathione peroxidase mimetic ebselen. Together, these studies suggest a novel role for GSH depletion in necroptotic astrocyte injury after a hemorrhagic injury and indicate that therapeutic targeting of GSH may exert a beneficial effect after ICH.

Cephalad Migration of Intradural Bullet from Thoracic Spine to Cervical Spine.

BACKGROUND: There are few reported instances of intraspinal migration of a bullet fragment. The majority of these migrations occur caudally, typically below the level of T10. Even fewer cases demonstrate cephalad migration from the sacral spine to the lumbar spine. We report here for the first time a case of a cephalad migration intradurally from the thoracic spine to cervical spine. CASE DESCRIPTION: A 31-year old man presented to the emergency department with a suspected spinal cord injury following a GSW sustained to the left shoulder. A penetrating gunshot injury to the thoracic spine at the level of T2 was observed, and CT angiography revealed a cephalad migration of the bullet fragment to the level of C6. The patient had marked weakness of the bilateral upper extremities, with paraplegia of the lower extremities. There was a sensory deficit beginning at a level 1 cm below the clavicle, as well as a decrease in rectal tone. We performed a laminectomy at C6 with dural incision and removal of the main bullet fragment. Following the surgery, significant improvement in strength and sensation in the bilateral upper extremities was noted, but paraplegia and sensory loss below the level of T2 persisted. CONCLUSIONS: In this report, we review the previously reported cases in which intraspinal migration of bullets have occurred, and discuss the unique finding in this study of cephalad migration of a bullet within the dura. In addition, we detail considerations in the management of such injuries.

[125 I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging.

Intracerebral hemorrhage (ICH) is a fatal stroke subtype with significant public health impact. Although neuroinflammation is a leading cause of neurological deficits after ICH, no imaging tool is currently available to monitor brain inflammation in ICH patients. Given the role of TSPO in neuroinflammation, herein we investigate whether a second-generation TSPO ligand, [125 I]IodoDPA-713 can be used to monitor the changes in TSPO expression in a preclinical model of intracerebral hemorrhage. Male CD1 mice were subjected to ICH/Sham. The brain sections, collected at different time points were incubated with [125 I]IodoDPA-713 and the brain uptake of [125 I]IodoDPA-713 was estimated using autoradiography. The specificity of [125 I]IodoDPA-713 binding was confirmed by a competitive displacement study with an unlabeled TSPO ligand, PK11195. [125 I]IodoDPA-713 binding was higher in the ipsilateral striatum with an enhanced binding observed in the peri-hematomal brain region after ICH, whereas the brain sections from sham as well as contralateral brain areas of ICH exhibited marginal binding of [125 I]IodoDPA-713. PK11195 completely reversed the [125 I] IodoDPA-713 binding to brain sections suggesting a specific TSPO-dependent binding of [125 I]IodoDPA-713 after ICH. This was further confirmed with immunohistochemistry analysis of adjacent sections, which revealed a remarkable expression of TSPO in the areas of high [125 I]IodoDPA-713 binding after ICH. The specific as well as enhanced binding of [125 I]IodoDPA-713 to the ipsilateral brain areas after ICH as assessed by autoradiography analysis provides a strong rationale for testing the applicability of [125 I]IodoDPA-713 for non-invasive neuroimaging in preclinical models of ICH.

Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent immune regulation.

Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality and worst outcomes of all stroke subtypes. Hematoma volume is an independent determinant of ICH patient outcomes, making clot resolution a primary goal of clinical management. Herein, remote-limb ischemic post-conditioning (RIC), the repetitive inflation-deflation of a blood pressure cuff on a limb, accelerated hematoma resolution and improved neurological outcomes after ICH in mice. Parabiosis studies revealed RIC accelerated clot resolution via a humoral-mediated mechanism. Whereas RIC increased anti-inflammatory macrophage activation, myeloid cell depletion eliminated the beneficial effects of RIC after ICH. Myeloid-specific inactivation of the metabolic regulator, AMPKα1, attenuated RIC-induced anti-inflammatory macrophage polarization and delayed hematoma resolution, providing a molecular link between RIC and immune activation. Finally, chimera studies implicated myeloid CD36 expression in RIC-mediated neurological recovery after ICH. Thus, RIC, a clinically well-tolerated therapy, noninvasively modulates innate immune responses to improve ICH outcomes. Moreover, immunometabolic changes may provide pharmacodynamic blood biomarkers to clinically monitor the therapeutic efficacy of RIC.

Carotid-Falciform Optic Neuropathy: Microsurgical Treatment.

BACKGROUND: Several recent reports have implicated vascular ectasia and vessel contact in dysfunction of the visual apparatus. A subset of patients with prechiasmatic visual deterioration have an ectatic internal carotid artery (ICA) that displaces and flattens the optic nerve (ON) rostrally as the ON exits the skull base. We describe a proposed pathophysiologic mechanism and a straightforward surgical technique for dealing with this problem. METHODS: Via an ipsilateral pterional craniotomy, the bony roof of the optic canal is removed. The falciform ligament is opened in parallel to the ON. Adhesions between the ICA and ON are then dissected, and a Teflon pledget is placed between the ICA and ON to complete the decompression. RESULTS: Patients both in the literature and in this series experienced an improvement in their vision postoperatively. CONCLUSIONS: We propose that 3 mechanisms contribute to this caroticofalciform optic neuropathy: 1) mass effect from ICA ectasia, 2) ON irritation from vessel pulsatility, and 3) indirect compression by the falciform ligament from above. This disease process can be treated safely using standard microsurgical techniques with excellent outcomes.

Resveratrol Attenuates Neurodegeneration and Improves Neurological Outcomes after Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a devastating type of stroke with a substantial public health impact. Currently, there is no effective treatment for ICH. The purpose of the study was to evaluate whether the post-injury administration of Resveratrol confers neuroprotection in a pre-clinical model of ICH. To this end, ICH was induced in adult male CD1 mice by collagenase injection method. Resveratrol (10 mg/kg) or vehicle was administered at 30 min post-induction of ICH and the neurobehavioral outcome, neurodegeneration, cerebral edema, hematoma resolution and neuroinflammation were assessed. The Resveratrol treatment significantly attenuated acute neurological deficits, neurodegeneration and cerebral edema after ICH in comparison to vehicle treated controls. Further, Resveratrol treated mice exhibited improved hematoma resolution with a concomitant reduction in the expression of proinflammatory cytokine, IL-1ß after ICH. Altogether, the data suggest the efficacy of post-injury administration of Resveratrol in improving acute neurological function after ICH.

Anterior Gray Matter Pituicytic Heterotopia with Monomorphic Anterior Pituitary Cells: A Variant of Nonsecretory Pituitary Adenoma Neuronal Choristoma? Report of a Rare Case and Review of the Literature.

BACKGROUND: Mixed tumors of adenomatous and neuronal cells in the sellar region are an uncommon finding. The origins of these heterogeneous tumors are unknown, and management remains unsettled. We report a very rare case of anterior gray matter pituicytic heterotopia with monomorphic anterior pituitary cells that likely represents a variant of nonsecreting pituitary adenoma neuronal choristoma (PANCH) with no ganglion cells. We also review the current literature for the various clinical presentations of PANCH. CASE DESCRIPTION: A 49-year-old female complaining of headache, blurred vision, and hair loss was found to have a nonsecretory sellar mass with compression of the optic chiasm on magnetic resonance imaging (MRI). The mass was excised via a transsphenoidal procedure. Histological analysis of tissue sections revealed heterotopic gray matter with reactive gliosis without ganglion cells or Herring bodies. Only 1 smear exhibited characteristics of a pituitary adenoma. CONCLUSIONS: The overall findings were most consistent with a variant of PANCH. At a postoperative follow-up of 4.5 years, there was resolution of visual symptoms, and the residual sellar mass was stable on MRI. Neuronal choristoma is hypothesized to originate from embryonal pituitary or hypothalamus, or by differentiation from pituitary adenoma cells. Surgery is the cornerstone of management, and the clinical course appears to be similar to that of nonfunctioning pituitary adenoma in reported cases.

Evolution of the treatment of cerebral vasospasm.

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a disease process for which the lack of effective treatments has plagued neurosurgeons for decades. Historically, successful treatment after SAH in the acute setting was often followed by a rapid, uncontrollable deterioration in the subacute interval. Little was known regarding the nature and progression of this condition until the mid-1800s, when the disease was first described by Gull. Insight into the origin and natural history of cerebral vasospasm came slowly over the next 100 years, until the 1950s. Over the past five decades our understanding of cerebral vasospasm has expanded exponentially. This newly discovered information has been used by neurosurgeons worldwide for successful treatment of complications associated with vasospasm. Nevertheless, although great strides have been made toward elucidating the causes of cerebral vasospasm, a lasting cure continues to elude experts and the disease continues to wreak havoc on patients after aneurysmal SAH.

Post-Injury Administration of Tert-butylhydroquinone Attenuates Acute Neurological Injury After Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a severe form of stroke with substantial public health impact. Notably, there is no effective treatment for ICH. Given the role of transcription factor Nrf2 (NF-E2-related factor 2) in antioxidant signaling, herein, we tested the efficacy of tert-butylhydroquinone (TBHQ), a selective inducer of Nrf2 in a preclinical model of ICH. Male CD1 mice were subjected to experimental intracerebral hemorrhage and administered intraperitoneally with TBHQ. The administration of TBHQ enhanced the DNA-binding activity of Nrf2 in the brain and reduced oxidative brain damage in comparison to vehicle-treated ICH. In addition, TBHQ treatment reduced microglial activation with concomitant reduction in the release of proinflammatory cytokine interleukin-1ß (IL-1 ß). Furthermore, TBHQ treatment attenuated neurodegeneration and improved neurological outcomes after ICH. Altogether, the data demonstrate the efficacy of post-injury administration of TBHQ in attenuating acute neurological injury after ICH.