Endoscopic endonasal transclival clipping of a cerebellar arteriovenous malformation feeding vessel and associated aneurysm; a 2D operative video.

Positioned along the ventral surface of the pons, proximal superior cerebellar artery (SCA) aneurysms account for only 1.7% of all intracranial aneurysms [1]. Unlike more commonly encountered basilar artery aneurysms, patients often experience good outcomes when treated via endovascular coiling or surgical clipping [1,2]. These lesions frequently have a lateral projection and paucity of perforator arteries [2]. With further development of endoscopic endonasal techniques, access to this region is possible via a direct frontal exposure to the ventral brainstem, basilar artery and branching vessels. To date, there are only a limited number of reports describing an endoscopic endonasal transclival (EETC) approach for surgical clipping [3-5]. In this operative video, we detail the surgical clipping of a cerebellar arteriovenous malformation feeding vessel and an associated aneurysm using the EETC approach in a 59-year-old woman who presented with sudden onset of a severe headache. The feeding vessel and aneurysm's midline location, just below the take-off of the SCA made it a good candidate for this surgery. Major steps included in this video include 1) transsphenoidal exposure of and subsequent drilling of the clivus, 2) dural opening into the pre-pontine cistern and dissection of the aneurysm, 3) clipping of the aneurysm, and 4) multi-layered closure of the skull base defect. Overall, the patient tolerated the procedure well and was found to have no residual filling of the aneurysm or the AVM feeding vessel at 2-year follow-up. EETC is a viable surgical option for the treatment of aneurysm located along the midline of the pre-pontine cistern.

Tandem cranial and spinal cerebrospinal fluid leaks presenting with otogenic tension pneumocephalus: illustrative case.

BACKGROUND: Cranial and spinal cerebrospinal fluid (CSF) leaks are associated with opposite CSF fluid dynamics. The differing pathophysiology between spontaneous cranial and spinal CSF leaks are, therefore, mutually exclusive in theory. OBSERVATIONS: A 66-year-old female presented with tension pneumocephalus. The patient underwent computed tomography (CT) scanning, which demonstrated left-sided tension pneumocephalus, with an expanding volume of air directly above a bony defect of the tegmen tympani and mastoideum. The patient underwent a left middle fossa craniotomy for repair of the tegmen CSF leak. In the week after discharge, she developed a recurrence of positional headaches and underwent head CT. Further magnetic resonance imaging of the brain and thoracic spine showed bilateral subdural hematomas and multiple meningeal diverticula. LESSONS: Cranial CSF leaks are caused by intracranial hypertension and are not associated with subdural hematomas. Clinicians should maintain a high index of suspicion for intracranial hypotension due to spinal CSF leak whenever "otogenic" pneumocephalus is found. Close postoperative follow-up and clinical monitoring for symptoms of intracranial hypotension in any patients who undergo repair of a tegmen defect for otogenic pneumocephalus is recommended.

Malignant progression of cerebellopontine angle solitary fibrous tumors following radiation: illustrative case.

BACKGROUND: Intracranial solitary fibrous tumors (ISFTs) are rare mesenchymal tumors originating in the meninges and constitute a heterogeneous group of clinical and biological behavior. Benign histotypes, such as hemangiopericytomas are now considered as a cellular phenotypic variant of this heterogenous group of rare spindle-cell tumors. IFSTs are poorly recognized and remain a diagnostic challenge due to rarity and resemblance to other brain tumors. Previously, IFSTs were thought to pursue a slow, indolent, and nonaggressive course, however, a growing body of literature based on longer follow-up demonstrates an unpredictable clinical course and an uncertain diagnosis. OBSERVATIONS: A rare case report of malignant transformation of IFST following radiation therapy is reported. In this case a 60-year-old female who underwent gross total resection of the cerebellopontine angle tumor with histopathology consistent with solitary fibrous tumor followed by salvage stereotactic radiosurgery, presented with another recurrence after 2 years of surgery. The authors performed complete removal of the tumor with pathology now consistent with malignant solitary fibrous tumor. A recent follow-up magnetic resonance imaging did not show any recurrence or residual tumor, and the patient reports a generalized well-being. LESSONS: This report will help to understand the natural history and unusual clinical behavior of these intracranial tumors.

Safety and Efficacy of Hypofractionated Stereotactic Radiosurgery in Facial Nerve Schwannoma.

OBJECTIVE: In the current era of modern neurosurgery, the treatment strategies have been shifted to "nerve-preservation approaches" for achieving a higher facial and hearing function preservation rate following facial nerve tumors. We have conducted this novel report on determining the outcome of patients with facial nerve schwannomas (FNS) treated with hypofractionated stereotactic radiosurgery (hfSRS). PATIENTS: Retrospective chart review of a prospectively maintained database search was conducted. INTERVENTION: Patients who underwent hfSRS CyberKnife (Accuray Inc, Sunnyvale, CA, U.S.A.) for FNS were included. MAIN OUTCOME MEASURES: Outcomes consisted of tumor control, facial and hearing nerve function as graded by House-Brackmann and American Academy of Otolaryngology-Head and Neck Surgery recommendations, and adverse radiation effects. RESULTS: With an institutional board review approval, we retrospectively identified five patients with FNS (four intracranial [80%] and one extracranial [20%]) treated with hfSRS (2011-2019). Patients received definitive SRS in three patients (60.0%), whereas adjuvant to surgical resection in two patients (40.0%). A median tumor volume of 7.5 cm 3 (range, 1.5-19.6 cm 3 ) received a median prescription dose of 23.2 Gy (range, 21-25 Gy) administered in median of three fractions (range, three to five sessions). With a median radiographic follow-up of 31.4 months (range, 13.0-71.0 mo) and clinical follow-up of 32.6 months (range, 15.1-72.0 mo), the local tumor control was 100.0%. At the last clinical follow-up, the facial nerve function improved or remained unchanged House-Brackmann I-II in 80.0% of the patients, whereas the hearing nerve function improved or remained stable in 100.0% of the patients. Temporary clinical toxicity was observed in three patients (60.0%), which resolved. None of the patients developed adverse radiation effect. CONCLUSION: From our case series, hfSRS in FNS seems to be safe and efficacious in terms of local tumor control, and improved facial and hearing nerve function.

The Role of Intra-Operative Duplex Ultrasonography Following Translabyrinthine Approach for Vestibular Schwannoma.

Objective: Sigmoid sinus (SS) stenosis is a complication of translabyrinthine approach. Velocity changes in the SS measured by intra-operative doppler ultrasound may help in identifying patients at risk for sinus occlusion. Patients: SS velocity was measured using doppler ultrasound prior to opening dura and again prior to placement of the abdominal fat graft. Intervention: Data collected included: patient age, surgical side, sinus dominance, tumor volume, intra-operative doppler ultrasound measurements, post-operative venous sinus imaging, anticoagulation, and morbidities and mortalities. Main Outcome Measure: SS patency and velocity. Results: Eight patients were included in the analysis (22 to 69 years). Four had left-sided and four had right-sided craniotomies. Sigmoid sinuses were either right-side dominant or co-dominant. The mean velocity ± standard deviation (SD) prior to dura opening and abdominal fat packing was 23.2 ± 11.3 and 25.5 ± 13.9 cm/s, respectively, p = 0.575. Post-operative Magnetic Resonance Venography (MRV) imaging showed four sigmoid sinus occlusions; seven patients showed sigmoid sinus stenosis, and one internal jugular vein occlusion. One patient had post-operative Computed Tomography Venography (CTV) only. Of the four patients with MRV occlusions, CTVs were performed with three showing occlusion and all four-showing stenosis. One patient with internal jugular vein occlusion on MRV received warfarin anticoagulation. There was one cerebrospinal fluid leak requiring ear closure, one small cerebellar infarct, and one with facial nerve palsy (House-Brackman Grade 3). Conclusion: SS velocity changes before and after tumor resection were not predictive of sinus occlusion. We hypothesize that sinus occlusion may be caused by related factors other than thrombosis, such as external compression of the sinus secondary to abdominal fat grafting.

Segmental spinal neurofibromatosis 1: a novel phenotype.

INTRODUCTION: Segmental neurofibromatosis (SNF) is a rare subtype of neurofibromatosis (NF). The disease is characterized by features circumscribed to one or more body cutaneous and/or subcutaneous segments. This is a classic example of somatic mosaicism which occurs by postzygotic mut ation of the NF1 gene late in the course of embryonic development affecting localized neural crest lines in the fetus. Spinal neurofibromatosis, on the other hand, is characterized by histologically proven bilateral neurofibromas of the spinal roots. METHODS: Hereby we describe a novel manifestation of spinal SNF. RESULTS: Our case report demonstrated one patient who had segmental spinal expression of the disease classified as true mosaic/segmental NF1 along with its management plan treated at one of the largest NF1 centers to exist. CONCLUSION: This will aid in understanding the rare clinical presentation and treatment options for this novel phenotype.

Predictors of hearing functional outcome following surgery for cerebellopontine angle meningioma.

OBJECTIVE: Cerebellopontine angle (CPA) meningiomas can affect hearing function and require expeditious treatment to prevent permanent hearing loss. The authors sought to determine the factors associated with functional hearing outcome in CPA meningioma patients treated with surgery and/or radiation therapy in the form of either stereotactic radiosurgery or stereotactic radiation therapy. METHODS: Consecutive patients with CPA meningiomas who had presented at our hospital from 2008 to 2018 were identified through retrospective chart review. Hearing function (as defined by pure tone average (PTA) and speech discrimination score (SDS) on Audiogram) was assessed before and after surgery for CPA meningioma. Audiograms with PTA > 50 dB and SDS < 69% were defined as poor hearing functional outcome. Multivariable Cox Proportional Hazards Regression Model was used to assess the associations between pre-operative hearing functional assessment and post-operative hearing functional outcomes. RESULTS: The study cohort included 31 patients (80.6% females, with a mean age of 61.3 ± 15.2 years) with a median clinical follow-up of 5 months (range: 1 week-98 months). The mean pre-operative PTA and SDS were 23.8 ± 11.2 dB and 64.4 ± 22.2% respectively. At the last visit, there was significant hearing recovery, with an improvement of 29.7 ± 18.0 dB (p < 0.001) and 87.6 ± 17.8% (p < 0.001) in PTA and SDS respectively. After adjusting for age, gender, tumor volume, location, and tumor classification, Multivariable Cox Proportional Hazards Regression Model was conducted which revealed that patients undergoing surgery through retro sigmoid approach [Hazards Ratio (HR): 32.1, 95% Confidence Interval (CI): 2.11-491.0, p = 0.01] and gross total resection (GTR) (HR: 2.99, 95% CI: 1.09-9.32, p = 0.05) had significantly higher risk of poor hearing functional outcome compared to petrosal approach and near/subtotal resection. Moreover, patients with poor preoperative hearing had 85% higher chance of poor hearing functional outcome postoperatively (HR: 0.15, 95%CI: 0.03-0.59, p = 0.007). CONCLUSION: Postoperative improvement in hearing is a reasonable expectation following surgery for CPA meningioma. Preoperative hearing, surgical approach and extent of surgical resection are predictive factors of postoperative hearing function outcome and can therefore aid in identification of patients at higher risk of hearing loss.

Encephaloduroarteriosynangiosis Operative Technique and Intraoperative Anesthesia Management: Treatment From Both Sides of the Curtain.

BACKGROUND: Encephaloduroarteriosynangiosis (EDAS) is a form of indirect revascularization for cerebral arterial steno-occlusive disorders. EDAS has gained growing interest as a technique applicable to pediatric and adult populations for several types of ischemic cerebral steno-occlusive conditions. OBJECTIVE: To present a team-oriented, multidisciplinary update of the EDAS technique for application in challenging adult cases of cerebrovascular stenosis/occlusion, successfully implemented in more than 200 cases. METHODS: We describe and demonstrate step-by-step a multidisciplinary-modified EDAS technique, adapted to maintain uninterrupted intensive medical management of patients' stroke risk factors and anesthesia protocols to maintain strict hemodynamic control. RESULTS: A total of 216 EDAS surgeries were performed in 164 adult patients, including 65 surgeries for patients with intracranial atherosclerotic disease and 151 operations in 99 patients with moyamoya disease. Five patients with intracranial atherosclerotic disease had recurrent strokes (3%), and there was one perioperative death. The mean clinical follow-up was 32.9 mo with a standard deviation of 31.1. There was one deviation from the surgical protocol. There were deviations from the anesthesia protocol in 3 patients (0.01%), which were promptly corrected and did not have any clinical impact on the patients' condition. CONCLUSION: The EDAS protocol described here implements a team-oriented, multidisciplinary adaptation of the EDAS technique. This adaptation resides mainly in 3 points: (1) uninterrupted administration of intensive medical management, (2) strict hemodynamic control during anesthesia, and (3) meticulous standardized surgical technique.

Role of cerebral digital subtraction angiography in the evaluation of pulse synchronous tinnitus.

OBJECTIVES: The aim of this study was to evaluate the value of digital subtraction angiography (DSA) in the diagnostic evaluation of a highly selected patient population presenting with pulse-synchronous tinnitus (PST). METHODS: We retrospectively reviewed the charts of all patients referred for evaluation of possible vascular etiology of pulsatile tinnitus. Patients were evaluated with regards to presenting signs, comorbidities, non-invasive imaging results, angiographic findings and outcomes. RESULTS: Fifteen patients underwent cerebral DSA. Dural arteriovenous fistula (dAVF) was identified in six patients, and five patients had other significant vascular pathology identified on DSA. Seven patients with 'negative' non-invasive imaging were found to have significant pathology on DSA. CONCLUSIONS: Catheter angiography may have a significant yield in appropriately selected patients presenting with pulse synchronous tinnitus.

Hypercoagulability in Vestibular Schwannoma Surgery.

OBJECTIVE: Patients with vestibular schwannoma who harbor a genetic predisposition for venous thromboembolism require special consideration when determining optimal therapeutic management. The primary objective of the current study was to provide recommendations on treatment of hypercoagulable patients with vestibular schwannoma through a case series and review of the literature. PATIENTS: Two patients who underwent resection of vestibular schwannomas. INTERVENTIONS: Surgical resection and diagnostic testing. MAIN OUTCOME MEASURES: Postoperative venous thromboses. RESULTS: One patient who underwent resection of vestibular schwannoma and suffered several postoperative thrombotic complications consistent with a clinical thrombophilia. One patient with known Factor V Leiden deficiency who underwent resection of vestibular schwannoma followed by postoperative chemoprophylaxis with a direct factor Xa inhibitor and experienced an uneventful postoperative course. CONCLUSIONS: In patients with a known propensity for venous thromboembolism, the skull base surgeon should consider nonsurgical management. If the patient undergoes surgical resection, we recommend careful effort to minimize trauma to the sigmoid sinus. In addition, the surgeon may consider retrosigmoid or middle fossa approaches. Best practice recommendations include the use of pneumatic compression devices, early ambulation, and consideration of postoperative prophylactic anticoagulation in patients with a known genetic predisposition.

Update in the treatment of intracranial atherosclerotic disease.

This review highlights the recent evolution of the imaging, medical management, surgical options and endovascular therapies for symptomatic intracranial atherosclerotic disease (ICAD). Recent imaging developments including optical coherence tomography and other modalities to assess the intracranial arteries for symptomatic ICAD are reviewed, not only to diagnose ICAD but to determine if ICAD plaques have any high-risk features for treatment. Potential future developments in the treatment of ICAD are discussed, including the development of trackable drug-coated balloons for the cerebral circulation to treat primary or restenotic arteries, new iterations of self-expanding intracranial stents with easier delivery systems, and the re-examination of indirect surgical bypass techniques for revascularisation. In addition to these important technological developments, however, is the evolving evidence regarding the best treatment window for these techniques and additional factors in medical management which can improve patient outcomes in this devastating pathology.

Hypofractionated Robotic Stereotactic Radiosurgery for Vagal Paragangliomas: A Novel Treatment Strategy for Cranial Nerve Preservation.

OBJECTIVE: To provide the first description of hypofractionated stereotactic radiosurgery (SRS) and evaluate tumor control and safety for vagal paragangliomas (VPs), which begin at the skull base but often have significant extracranial extension. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary-referral neurotology and neurosurgery practice. SUBJECTS AND METHODS: Five VPs in 4 patients (all male, ages 15-56 years) underwent SRS between 2010 and 2018. Outcome measures included tumor dimensions on serial imaging, cranial nerve function, and radiation side effects. RESULTS: CyberKnife hypofractionated SRS was performed. The prescription dose was 24 or 27 Gy (maximum dose 33.4 Gy; range, 29.3-35.5 Gy) delivered in 3 equal fractions. The mean isodose line was 79% (range, 76%-82%). Four VPs were treated primarily, and 1 tumor underwent SRS to treat regrowth 2 years after microsurgical subtotal resection via the modified infratemporal fossa approach. The treatment volume ranged from 8.81 to 86.3 cm3 (mean, 35.7 cm3). All demonstrated stable size (n = 3) or regression (n = 2) at last follow-up, 63 to 85 months after SRS (mean, 76 months). One patient had stable premorbid vocal fold paralysis from a prior ipsilateral glomus jugulare tumor resection. All others demonstrated normal vagal function following SRS. Treatment-related side effects, including dysgeusia (n = 1), mucositis (n = 1), and neck soft-tissue edema (n = 2), were self-limited. CONCLUSIONS: Hypofractionated SRS appears to be both safe and effective for treating VPs, including large-volume and predominantly extracranial tumors, while preserving vagal function. SRS should be considered as a cranial nerve preservation option, especially in settings of contralateral lower cranial nerve deficits or in those with multiple paragangliomas risking both vagal nerves.

Device profile of the Wingspan Stent System for the treatment of intracranial atherosclerotic disease: overview of its safety and efficacy.

Introduction: This Wingspan Stent is a self-expanding, laser-cut, nitinol stent designed for the treatment of severe symptomatic intracranial artery stenosis to be used in conjunction with the Gateway angioplasty balloon. This review will describe the technical features of the stent, its composition, design, and functional characteristics, as well as an overview of its safety and efficacy.Areas covered: The engineering and manufacturing specifications are described for the stent. A systematic review of the literature from 2005 to 2019 is performed to define the safety profile of the stent as an implant for cerebral artery revascularization, stroke prophylaxis, and acute stroke treatment. These reports are compared to the published reports of patients with similar characteristics treated with medical therapy alone.Expert opinion: Although prior off-label studies have shown variable results, recent on-label studies have shown that the Wingspan stent itself is very safe, with low complication rates, and that it may confer long-term benefits in stroke prevention compared to medical therapy alone. Provided that established guidelines are followed, the Wingspan stent is effective in cerebral artery revascularization, and improves clinical outcomes in acute large vessel occlusive stroke with underlying intracranial atherosclerotic stenosis.

Growth hormone-secreting pituitary macroadenoma presenting concurrently with non-Hodgkin's lymphoma and responding to doxorubicin treatment: case report and review of the literature.

We present a case report of a patient who presented with nausea and vomiting, as well as acromegalic features. Following testing, a pituitary adenoma and mediastinal non-Hodgkin's lymphoma were diagnosed. Following two cycles of R-CHOP chemotherapy, imaging showed significant decrease in size of the sellar tumor. Following resection of tumor, both frozen and permanent section revealed only necrotic material. Further research into the potential utility of doxorubicin for the treatment of recurrent or refractory pituitary adenomas may be warranted.

Behavioral Variant Frontotemporal Dementia as a Serious Complication of Spontaneous Intracranial Hypotension.

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is a devastating early onset dementia. Symptoms of bvFTD may be caused by spontaneous intracranial hypotension (SIH), a treatable disorder, but no comprehensive study of such patients has been reported. OBJECTIVE: To describe detailed characteristics of a large cohort of patients with SIH and symptoms of bvFTD. METHODS: We identified patients with SIH who met clinical criteria for bvFTD. Patients were compared to a cohort of SIH patients without bvFTD. RESULTS: The mean age for the 21 men and 8 women was 52.9 yr (range, 37-65 yr). All 29 patients with bvFTD symptoms had hypersomnolence. Magnetic resonance imaging showed brain sagging in all patients, cerebrospinal fluid (CSF) opening pressure low in about half of patients, but a spinal CSF leak could not be detected in any patient. All patients underwent epidural blood patching, but 26 patients eventually underwent 1 or more surgical procedures. Overall, a good outcome was obtained in 21 patients (72%); 20 (91%) of 22 patients who had not undergone prior Chiari surgery compared to 1 (14%) of 7 patients who did undergo Chiari surgery (P < .003). Compared to SIH patients without symptoms of bvFTD (n = 547), those with bvFTD symptoms were older, more often male, less often demonstrated CSF leak on spinal imaging, and more often underwent surgery (P < .02). CONCLUSION: bvFTD in SIH is rare and associated with brain sagging and hypersomnolence. Spinal CSF leaks are rarely detected. bvFTD symptoms are often refractory to the usual percutaneous procedures but most patients can be cured.

Limit Crystalloid Resuscitation after Traumatic Brain Injury.

Patients with traumatic brain injury (TBI) are often resuscitated with crystalloids in the emergency department (ED) to maintain cerebral perfusion. The purpose of this study was to evaluate whether crystalloid resuscitation volume impacts mortality in TBI patients. This was a retrospective study of trauma patients with head abbreviated injury scale score ≥2, who received crystalloids during ED resuscitation between 2004 and 2013. Clinical characteristics and volume of crystalloids received in the ED were collected. Patients who received <2 L of crystalloids were categorized as low volume (LOW), whereas those who received ≥2 L were considered high volume (HIGH). Mortality and outcomes were compared. Multivariable regression analysis was used to determine the odds of mortality while controlling for confounders. Over 10 years, 875 patients met inclusion criteria. Overall mortality was 12.5 per cent. Seven hundred and forty-two (85%) were in the LOW cohort and 133 (15%) in the HIGH cohort. Gender and age were similar between the groups. The HIGH cohort had lower admission systolic blood pressure (128 vs 138 mm Hg, P = 0.001), lower Glasgow coma scale score (10 vs 12, P < 0.001), higher head abbreviated injury scale (3.8 vs 3.3, P < 0.001), and higher injury severity score (25 vs 18, P < 0.001). The LOW group had a lower unadjusted mortality (10 vs 26%, P < 0.001). Multivariable analysis adjusting for confounders demonstrated that those resuscitated with ≥2 L of crystalloids had increased odds of mortality (adjusted odds ratio 2.25, P = 0.005). Higher volume crystalloid resuscitation after TBI is associated with increased mortality, thus limited resuscitation for TBI patients may be indicated.

Adult Brainstem Glioblastoma Multiforme: Long-term Survivor.

Adult, malignant brainstem gliomas are rare entities that often cause treatment conundrums due to the difficulty of surgical resection and, therefore, the absence of pathological diagnosis. This leads to a reliance on radiological imaging for diagnosis, which can often be unreliable. These shortcomings have made the treatment of brainstem gliomas challenging with unpredictable outcomes. The mainstay of treatment consists of chemotherapy and radiation; however, recurrence is inevitable. Predicting outcomes has been the major difficulty in treating these patients as adult malignant brainstem gliomas Grade II have a median survival between five to seven years while Grades III and IV are between 10-17 months (with some studies showing significantly longer survival in Grade III). Here, we present the case of a patient with the pathologic diagnosis of a right brachium pontis glioblastoma who had a remarkable survival of 73 months, whereas the expected median survival for these patients is 10-17 months.

Robotics and the spine: a review of current and ongoing applications.

OBJECT: Robotics in the operating room has shown great use and versatility in multiple surgical fields. Robot-assisted spine surgery has gained significant favor over its relatively short existence, due to its intuitive promise of higher surgical accuracy and better outcomes with fewer complications. Here, the authors analyze the existing literature on this growing technology in the era of minimally invasive spine surgery. METHODS: In an attempt to provide the most recent, up-to-date review of the current literature on robotic spine surgery, a search of the existing literature was conducted to obtain all relevant studies on robotics as it relates to its application in spine surgery and other interventions. RESULTS: In all, 45 articles were included in the analysis. The authors discuss the current status of this technology and its potential in multiple arenas of spinal interventions, mainly spine surgery and spine biomechanics testing. CONCLUSIONS: There are numerous potential advantages and limitations to robotic spine surgery, as suggested in published case reports and in retrospective and prospective studies. Randomized controlled trials are few in number and show conflicting results regarding accuracy. The present limitations may be surmountable with future technological improvements, greater surgeon experience, reduced cost, improved operating room dynamics, and more training of surgical team members. Given the promise of robotics for improvements in spine surgery and spine biomechanics testing, more studies are needed to further explore the applicability of this technology in the spinal operating room. Due to the significant cost of the robotic equipment, studies are needed to substantiate that the increased equipment costs will result in significant benefits that will justify the expense.

Hyponatremia associated with Ipilimumab-induced hypophysitis.

A 75-year-old woman with a history of stage IV metastatic melanoma underwent treatment with the CTLA-4 blocking agent Ipilimumab. She presented 2 months after initiating treatment with a severe headache. Laboratories were consistent with severe hyponatremia. MRI of the brain revealed enlargement of the pituitary gland, enhancement of the infundibulum, and an enhancing, centrally necrotic foci in the anterior pituitary. Based on the clinical and radiographic findings, she was diagnosed with treatment-related syndrome of inappropriate antidiuretic hormone secretion (SIADH). Effective treatment consisted of fluid restriction, hyperosmolar therapy, and steroids.

Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells.

The clinicopathological heterogeneity of glioblastoma (GBM) and the various genetic and phenotypic subtypes in GBM stem cells (GSCs) are well described. However, the relationship between GSCs and the corresponding primary tumor from which they were isolated is poorly understood. We have established GSC-enriched neurosphere cultures from 15 newly diagnosed GBM specimens and examined the relationship between the histopathological and genomic features of GSC-derived orthotopic xenografts and those of the respective patient tumors. GSC-initiated xenografts recapitulate the distinctive cytological hallmarks and diverse histological variants associated with the corresponding patient GBM, including giant cell and gemistocytic GBM, and primitive neuroectodermal tumor (PNET)-like components. This indicates that GSCs generate tumors that preserve patient-specific disease phenotypes. The majority of GSC-derived intracerebral xenografts (11 of 15) demonstrated a highly invasive behavior crossing the midline, whereas the remainder formed discrete nodular and vascular masses. In some cases, GSC invasiveness correlated with preoperative MRI, but not with the status of PI3-kinase/Akt pathways or O(6)-methylguanine methyltransferase expression. Genome-wide screening by array comparative genomic hybridization and fluorescence in situ hybridization revealed that GSCs harbor unique genetic copy number aberrations. GSCs acquiring amplifications of the myc family genes represent only a minority of tumor cells within the original patient tumors. Thus, GSCs are a genetically distinct subpopulation of neoplastic cells within a GBM. These studies highlight the value of GSCs for preclinical modeling of clinically relevant, patient-specific GBM and, thus, pave the way for testing novel anti-GSC/GBM agents for personalized therapy.