Altering biomolecular condensates as a potential mechanism that mediates cannabidiol effect on glioblastoma.

Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2α (eIF2α). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2α expression and p-eIF2α in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.

Endoscopic-Assisted Microsurgical Resection of a Recurrent Conus Medullaris Dermoid Tumor.

Surgery for intramedullary spinal cord tumors presents multiple unique challenges, including the need to operate through a very narrow myelotomy window. In this operative video, we demonstrate the use of the surgical endoscope in an operation performed on a 35-year-old woman. She has a history of conus medullaris dermoid tumor resection, and she presented to us with worsening lower extremity sensory and motor symptoms. Magnetic resonance imaging showed a 4-cm recurrence of her tumor. After consenting to surgery, she underwent reoperative posterior lumbar approach to resection of her tumor. In our video we demonstrate our use of a surgical endoscope, which allowed us to minimize the extent of our myelotomy and resect tumor rostral and caudal to our myelotomy, thus minimizing the risk of damage to normal spinal cord that is displaced by tumor (Video 1).

Endoscope-assisted far lateral craniotomy for resection of posterior fossa neurocysticercosis: illustrative case.

BACKGROUND: Neurocysticercosis is a parasitic infection that commonly affects the ventricles, subarachnoid spaces, and spinal cord of the central nervous system. The authors report an unusual manifestation of purely posterior fossa neurocysticercosis treated with endoscope-assisted open craniotomy for resection. OBSERVATIONS: A 67-year-old male presented with 2 months of progressive dizziness, gait ataxia, headaches, decreased hearing, and memory impairment. Imaging revealed an extra-axial cystic lesion occupying the foramen magnum and left cerebellopontine angle with significant mass effect and evidence of early hydrocephalus. Gross-total resection was accomplished via a left far lateral craniotomy with open endoscopic assistance, and pathological findings were consistent with neurocysticercosis. Postoperatively, he was noted to have a sixth nerve palsy, and adjuvant therapy included albendazole. By 9 months postoperatively, he exhibited complete resolution of an immediate postoperative sixth nerve palsy in addition to all preoperative symptoms. His hydrocephalus resolved and did not require permanent cerebrospinal fluid (CSF) diversion. LESSONS: When combined with traditional skull base approaches, open endoscopic techniques allow for enhanced visualization and resection of complex lesions otherwise inaccessible under the microscope alone. Recognition and obliteration of central nervous system neurocysticercosis can facilitate excellent neurological recovery without the need for CSF diversion.

Pretemporal Transcavernous Approach for Resection of an Orbito-Cavernous Oculomotor Schwannoma.

The following operative video demonstrates surgical tenets and nuances of the pretemporal transcavernous approach in an unusual case of a 33-year-old patient suffering new onset diplopia and a third nerve palsy due to an orbito-cavernous oculomotor schwannoma. Near total resection was accomplished through an extended pterional craniotomy with pretemporal transcavernous exposure of her lesion, resulting in resolution of her preoperative oculomotor palsy and visual dysfunction. When combined with extended pterional and modified frontotemporal orbitozygomatic approaches, the pretemporal transcavernous approach provides excellent surgical access to the parasellar region including the superior orbital fissure and cavernous sinus. Meticulous dissection and early identification of tissue planes, including cranial nerve and vascular anatomy, allows for safe removal of tumors arising in this region. The link to the video can be found at: https://youtu.be/EuIRTP7wWBQ .

Treatment strategies for giant pituitary adenomas in the era of endoscopic transsphenoidal surgery: a multicenter series.

OBJECTIVE: Given the anatomical complexity and frequently invasive growth of giant pituitary adenomas (GPAs), individually tailored approaches are required. The aim of this study was to assess the treatment strategies and outcomes in a large multicenter series of GPAs in the era of endoscopic transsphenoidal surgery (ETS). METHODS: This was a retrospective case-control series of 64 patients with GPAs treated at two tertiary care centers by surgeons with experience in ETS. GPAs were defined by a maximum diameter of ≥ 4 cm and a volume of ≥ 10 cm3 on preoperative isovoxel contrast-enhanced MRI. RESULTS: The primary operation was ETS in all cases. Overall gross-total resection rates were 64% in round GPAs, 46% in dumbbell-shaped GPAs, and 8% in multilobular GPAs (p < 0.001). Postoperative outcomes were further stratified into two groups based on extent of resection: group A (gross-total resection or partial resection with intracavernous remnant; 21/64, 33%) and group B (partial resection with intracranial remnant; 43/64, 67%). Growth patterns of GPAs were mostly round (11/14, 79%) in group A and multilobular (33/37, 89%) in group B. In group A, no patients required a second operation, and 2/21 (9%) were treated with adjuvant radiosurgery. In group B, early transcranial reoperation was required in 6/43 (14%) cases due to hemorrhagic transformation of remnants. For the remaining group B patients with remnants, 5/43 (12%) underwent transcranial surgery and 12/43 (28%) underwent delayed second ETS. There were no deaths in this series. Severe complications included stroke (6%), meningitis (6%), hydrocephalus requiring shunting (6%), and loss or distinct worsening of vision (3%). At follow-up (mean 3 years, range 0.5-16 years), stable disease was achieved in 91% of cases. CONCLUSIONS: ETS as a primary treatment modality to relieve mass effect in GPAs and extent of resection are dependent on GPA morphology. The pattern of residual pituitary adenoma guides further treatment strategies, including early transcranial reoperation, delayed endoscopic transsphenoidal/transcranial reoperation, and adjuvant radiosurgery.

Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

OBJECTIVE: Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. METHODS: The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. RESULTS: The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. CONCLUSIONS: Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

Development and clinical validation of a grading system for pituitary adenoma consistency.

OBJECTIVE: Pituitary adenoma (PA) consistency, or texture, is an important intraoperative characteristic that may dictate operative dissection techniques and/or instruments used for tumor removal during endoscopic endonasal approaches (EEAs). The impact of PA consistency on surgical outcomes has yet to be elucidated. METHODS: The authors developed an objective 5-point grading scale for PA consistency based on intraoperative characteristics, including ease of tumor debulking, manipulation, and instrument selection, ranging from cystic/hemorrhagic tumors (grade 1) to calcified tumors (grade 5). The proposed grading system was prospectively assessed in 306 consecutive patients who underwent an EEA for PAs, and who were subsequently analyzed for associations with surgical outcomes, including extent of resection (EOR) and complication profiles. RESULTS: Institutional database review identified 306 patients who underwent intraoperative assessment of PA consistency, of which 96% were macroadenomas, 70% had suprasellar extension, and 44% had cavernous sinus invasion (CSI). There were 214 (69.9%) nonfunctional PAs and 92 functional PAs (31.1%). Distribution of scores included 15 grade 1 tumors (4.9%), 112 grade 2 tumors (36.6%), 125 grade 3 tumors (40.8%), 52 grade 4 tumors (17%), and 2 grade 5 tumors (0.7%). Compared to grade 1/2 and grade 3 PAs, grade 4/5 PAs were significantly larger (22.5 vs 26.6 vs 27.4 mm, p < 0.01), more likely to exhibit CSI (39% vs 42% vs 59%, p < 0.05), and trended toward nonfunctionality (67% vs 68% vs 82%, p = 0.086). Although there was no association between PA consistency and preoperative headaches or visual dysfunction, grade 4/5 PAs trended toward preoperative (p = 0.058) and postoperative panhypopituitarism (p = 0.066). Patients with preoperative visual dysfunction experienced greater improvement if they had a grade 1/2 PA (p < 0.05). Intraoperative CSF leaks were noted in 32% of cases and were more common with higher-consistency-grade tumors (p = 0.048), although this difference did not translate to postoperative CSF leaks. Gross-total resection (%) was more likely with lower PA consistency score as follows: grade 1/2 (60%), grade 3 (50%), grade 4/5 (44%; p = 0.045). Extracapsular techniques were almost exclusively performed in grade 4/5 PAs. Assignment of scores showed low variance and high reproducibility, with an intraclass correlation coefficient of 0.905 (95% CI 0.815-0.958), indicating excellent interrater reliability. CONCLUSIONS: These findings demonstrate clinical validity of the proposed intraoperative grading scale with respect to PA subtype, neuroimaging features, EOR, and endocrine complications. Future studies will assess the relation of PA consistency to preoperative MRI findings to accurately predict consistency, thereby allowing the surgeon to tailor the exposure and prepare for varying resection strategies.

Transblepharo-Preseptal Modified Orbitozygomatic Approach for Resection of Giant Frontal Cavernous Malformation: 3-Dimensional Operative Video.

A previously healthy 44-year-old woman presented with a first-time seizure. Magnetic resonance imaging (MRI) revealed a right frontal intraaxial mass extending from the orbitofrontal gyri and gyrus rectus to the head of the caudate (Video 1). The mass demonstrated heterogeneous signal intensity on precontrast T1-weighted MRI, minimal contrast enhancement, and mixed intensity on gradient echo MRI sequence consistent with a likely cavernous malformation. Given the location above the orbital roof with cranial-caudal extension to the level of the caudate, a transblepharo-preseptal modified orbitozygomatic craniotomy was recommended. With the assistance of plastic surgery, the lesion was approached through an eyelid incision that extended laterally to expose the keyhole. A McCarty burr hole was made, followed by a tailored orbitozygomatic craniotomy with osteotomies extending through the superolateral orbit and greater sphenoid wing to expose the proximal sylvian fissure. Dura was opened in a C-shaped fashion over the periorbital fat to allow for mild downward retraction of the globe, exposing the subfrontal trajectory. The opticocarotid cistern was opened to allow for cerebrospinal fluid egress and relaxation, and the lesion was readily identified through the use of stereotactic neuronavigation and presence of a faint hemosiderin blush within the underlying parenchyma. The standard microsurgical technique was used to perform a gross total resection of the pathologically confirmed cavernous malformation. The orbitozygomatic bone flap was replaced and plated, and the wound was closed in multiple layers. The patient was seen at a 3-month follow-up without further seizures.

Differential Clinical Presentation, Intraoperative Management Strategies, and Surgical Outcomes After Endoscopic Endonasal Treatment of Cystic Sellar Masses.

BACKGROUND: Cystic sellar masses (CSMs) pose diagnostic and therapeutic challenges associated with subtotal cyst wall resection, cerebrospinal fluid (CSF) leak repair, and disease recurrence. Current magnetic resonance imaging (MRI) interpretation often cannot reliably differentiate CSMs, mandating adaptable intraoperative strategies. We reviewed our diagnostic and therapeutic experience after endoscopic endonasal approaches (EEAs) for CSMs. METHODS: A retrospective record review of patients with CSM managed via EEA at the University of Southern California from 2011 to 2018 was conducted. Patient demographics, preoperative characteristics, surgical details, pathologic findings, and postoperative outcomes were assessed. RESULTS: Analysis included 47 patients (mean age, 43.2 years); of these, 78.7% were women. Preoperative symptoms included headache (76.6%) and vision loss (42.6%). Histologically verified sellar pathology included 27 Rathke cleft cysts (RCCs) (57.4%), 17 cystic pituitary adenomas (CPAs) (36.2%), 2 arachnoid cysts (4.3%), and 1 xanthogranuloma (2.1%). Twelve patients (70.6%) with CPAs underwent complete resection and 5 (29.4%) underwent subtotal resection. All 27 patients with RCC and 2 patients with arachnoid cyst underwent complete fenestration and drainage. One xanthogranuloma was completely resected. There were 14 intraoperative (29.8%) and 4 postoperative CSF leaks (8.5%). Headaches, vision, and endocrinopathy improved in 69.2%, 80.0%, and 33.3% of patients with CPA and 73.9%, 71.4%, and 40.9% of patients with RCC, respectively. There were 2 RCC recurrences and 1 CPA recurrence over the follow-up period. CONCLUSIONS: Surgeons must prepare for versatile management strategies of CSMs based on pretest probability associated with MRI and intraoperative findings. Outcomes after EEA for CSMs show low complication profiles and excellent rates of headache and visual improvement, albeit lower rates of endocrine normalization.

Sporadic and Von-Hippel Lindau disease-associated spinal hemangioblastomas: institutional experience on their similarities and differences.

INTRODUCTION: Hemangioblastomas are uncommon tumors of the central nervous system that can be seen in Von Hippel-Lindau (VHL) disease. Despite their benign histology, hemangioblastomas can cause substantial morbidity due to involvement of critical structures. In order to better understand the clinical behavior of spinal cord hemangioblastomas, we have analyzed the clinical, pathologic, radiologic characteristics and management of sporadic and VHL-associated cases at our institution. METHODS: We performed a database search to identify all spinal hemangioblastomas at our institution between 1997 and 2016. Tumor characteristics were analyzed for sporadic and VHL-associated tumors separately in order to understand the differences in groups. RESULTS: We included 20 patients with VHL-associated spinal hemangioblastomas, and 22 patients with sporadic spinal hemangioblastomas. VHL-associated patients were significantly younger at time of presentation compared to sporadic patients (p < 0.0025). Thirty-two patients (76.2%) presented with focal weakness, 34 (81.0%) with sensory loss, and 22 (52.4%) with pain. VHL patients were more likely to present with multiple symptoms (p < 0.001). Median follow-up time was 20.9 months, during which 17 tumors recurred. The median recurrence free interval was 44 months. There were no differences in gross total resection rates between sporadic and VHL-associated cases (p = 0.197). VHL-associated cases had a higher rate of repeat surgery for recurrence (14 patients-73.6%) compared to sporadic cases (3 patients-13.6%; p < 0.001). CONCLUSION: VHL-associated spinal hemangioblastomas differ from sporadic tumors in terms of age, presenting symptoms, multifocality, and rate of recurrence. Recurrences seem to be unrelated to the extent of resection, indicating the need for life-long follow up for VHL patients.

Medical versus surgical treatment of prolactinomas: an analysis of treatment outcomes.

INTRODUCTION: Prolactinomas are unique tumors that may go into both hormonal and radiographic remission with dopamine agonist therapy or transsphenoidal surgery. Regardless of modality, the goals of therapy remain the same: (1) biochemical remission, including reduction of prolactin and normalization of sex hormones; (2) radiographic tumor control, with a range including prevention of tumor growth, tumor regression, or complete tumor resolution; (3) resolution of preoperative symptoms, including those that are hormonal or neurologic; and (4) prevention of new hypopituitarism or new neurologic symptoms. AREAS COVERED: In the following review, we performed a search of the literature using keywords 'prolactinoma,' 'dopamine agonist,' 'surgery,' 'cost-effectiveness,' 'recurrence,' and 'complication' to compare the relative merits of medical versus surgical therapy for prolactinoma, including special circumstances such as cystic tumors, pregnant patients, and the cost-effectiveness of different strategies. EXPERT COMMENTARY: Medical therapy can offer a cure, but surgery provides an important adjunct to patients with resistance or intolerance to dopamine agonists, and offers excellent outcomes including when combined with continued postoperative medical therapy. Further head to head comparisons will benefit patients and practitioners weighing the relative risks and benefits of medical and surgical intervention, including the issue of their relative cost-effectiveness.

Surgical intervention for pituitary apoplexy: an analysis of functional outcomes.

OBJECTIVE Pituitary apoplexy is a clinical syndrome consisting of neurological and endocrine abnormalities secondary to hemorrhage or ischemia of an underlying pituitary adenoma. The authors investigated whether there was a significant difference in neurological, endocrine, and nonneuroendocrine outcomes for patients with pituitary apoplexy, based on the time between symptom onset and surgical intervention. METHODS The authors retrospectively analyzed the medical records of 32 patients who had presented to their institution with acute pituitary apoplexy and subsequently undergone endonasal transsphenoidal resection in the period from 2003 to 2014. All patients had undergone preoperative MRI demonstrating evidence of apoplexy in the form of intratumoral hemorrhage, ischemia, and necrosis. Neurological deficits, partial or complete endocrinopathy, and nonneuroendocrine abnormalities were analyzed both pre- and postoperatively. RESULTS Preoperatively, neurological deficits including visual loss and cranial nerve palsies were found in 31 (97%) of the 32 patients, endocrinopathy in the form of partial or panhypopituitarism was seen in 28 patients (88%), and nonneuroendocrine signs and symptoms were seen in 32 patients (100%). Thirteen patients (41%) underwent surgery within 72 hours of symptom onset ("early"), whereas 19 patients (59%) underwent surgery more than 72 hours from symptom onset ("delayed"). Early versus delayed resection did not appear to significantly improve visual deficits, total visual loss, resolution of oculomotor palsy, recovery from hypopituitarism, or nonneuroendocrine signs and symptoms such as headache and encephalopathy. Overall, visual improvement was seen in 77% of patients, complete restoration of normal vision in 38% of patients, and resolution of preoperative oculomotor palsies in 81% of patients. Only 6 (21%) of 28 patients showed evidence of partial hormone recovery following preoperative hypopituitarism. An absence of benefit for early surgery held true even when considering time to surgery from symptom onset as a continuous variable. CONCLUSIONS Neurological deficits such as visual loss and cranial neuropathies show moderate improvement following surgical decompression, as does preoperative hypopituitarism. The timing of surgical intervention relative to the onset of symptoms does not appear to significantly affect the resolution of neurological or endocrinological deficits.

Before and after the veterans affairs cooperative program 468 study: Deep brain stimulator target selection for treatment of Parkinson's disease.

INTRODUCTION: The Veterans Affairs Cooperative Study Program 468 study (CSP 468) produced significant findings regarding deep brain stimulation (DBS) target selection for Parkinson's Disease (PD) treatment, yet its impact on clinical practices has not been described. Here we assess how CSP 468 influenced target selection at a high-volume movement disorders treatment center. METHODS: We compared DBS target site selection between 4-year periods that immediately preceded and followed CSP 468 publication. Additionally, we examined how baseline clinical features influenced target selection following CSP 468. RESULTS: The STN was the predominant site of DBS implantation before and after CSP 468 publication (93.2% of cases, and 60.4%, respectively), but GPi targeting increased significantly following CSP 468 publication (from 5.3% to 37.4%; p < .001). Patients who underwent GPi stimulation following CSP 468 exhibited worse indices of depression (p < .001), less responsiveness to medications (p < .05), and a trend towards worse pre-operative cognitive performance (p = .06). In multi-variate analysis, advanced patient age and depression were independent predictors of GPi targeting (p < .01). CONCLUSIONS: Key findings of CSP 468 were reflected in our target selection of DBS for Parkinson's Disease. Following CSP 468, GPi targeting increased, and it was selected for patients with poorer cognitive and mood indices.

Atypical pituitary adenoma: a clinicopathologic case series.

OBJECTIVE In 2004, the WHO classified atypical pituitary adenoma as a distinct adenoma subtype. However, the clinical significance of this distinction remains undetermined. The authors sought to define patient characteristics, tumor features, and treatment outcomes associated with atypical pituitary adenoma. METHODS The authors reviewed records of patients who underwent resection of pituitary adenoma at the University of California, San Francisco, between 2007 and 2014. Per institutional protocol, adenomas exhibiting mitotic activity underwent evaluation for all 3 markers of atypicality (mitotic index, extensive p53 staining, and MIB-1 index ≥ 3%). Statistical analyses were performed using χ2, Fisher's exact test, t-test, log-rank, and logistic regression. RESULTS Between 2007 and 2014, 701 patients underwent resection for pituitary adenoma. Among these patients, 122 adenomas exhibited mitotic activity and therefore were evaluated for all 3 markers of atypicality, with 36 tumors (5%) proving to be atypical. There were 21 female patients (58%) and 15 male patients (42%) in the atypical cohort, and 313 female patients (47%) and 352 male patients (53%) in the nonatypical cohort (p = 0.231). The mean age of patients in the atypical cohort was 37 years (range 10-65 years), which was significantly lower than the mean age of 49 years (range 10-93 years) for patients in the nonatypical cohort (p < 0.001). The most common presenting symptoms for patients with atypical adenomas were headaches (42%) and visual changes (33%). Atypical adenomas were more likely to be functional (78%) than nonatypical adenomas (42%; p < 0.001). Functional atypical adenomas were significantly larger than functional nonatypical adenomas (mean diameter 2.2 vs 1.4 cm; p = 0.009), as were nonfunctional atypical adenomas compared with nonfunctional nonatypical adenomas (mean diameter 3.3 vs 2.3 cm; p = 0.01). Among the entire adenoma cohort, larger presenting tumor size was associated with cavernous sinus invasion (p < 0.001), and subtotal resection was associated with cavernous sinus invasion (p < 0.001) and larger size (p < 0.001) on binomial multivariate regression. The median time until recurrence was 56 months for atypical adenomas, 129 months for functional nonatypical adenomas, and 204 months for nonfunctional nonatypical adenomas (p < 0.001). Functional atypical adenomas recurred more frequently and significantly earlier than functional nonatypical adenomas (p < 0.001). When accounting for extent of resection, cavernous sinus invasion, size, age, sex, and functional subtype, atypicality remained a significant predictor of earlier recurrence among functional adenomas (p = 0.002). CONCLUSIONS When compared with nonatypical pituitary adenomas, atypical adenomas are more likely to present in younger patients at a larger size, are more often hormonally hypersecretory, and are associated with earlier recurrence. These features lend credence to atypical pituitary adenomas being a distinct clinical entity in addition to a discrete pathological diagnosis.

Surgical management of cerebral dural arteriovenous fistulae.

Dural arteriovenous fistulae are high flow, low resistance intracranial vascular malformations defined by an aberrant connection between an artery and dural vein or sinus. Symptomatology and presentation are highly dependent on location, generally categorized as supratentorial, tentorial, or infratentorial, and consist primarily of sequelae secondary to local venous hypertension, insufficiency, and cortical venous reflux. Surgery is generally reserved for high risk or persistently symptomatic lesions that are unamenable or unresponsive to endovascular therapy. For surgical lesions, familiarity with skull base approaches, specific fistula anatomy, and technical nuances based on fistula location offer patients the best chance of a favorable outcome.

Metastatic clival chordoma: a case report of multiple extraneural metastases following resection and proton beam radiotherapy in a 5-year old boy.

The authors report the case of a 5-year-old boy in whom extraneural metastases developed 5 years after he underwent an occipitocervical fusion and transoral approach to treat a clival chordoma without local recurrence. Following primary resection, the patient's postoperative course was complicated by recurrent meningitis secondary to CSF leak, which responded to antibiotics, and communicating hydrocephalus, for which a ventriculoperitoneal shunt was placed. The patient then underwent postoperative proton beam radiotherapy. Five years following his initial presentation, surveillance imaging revealed a new asymptomatic lung mass for which the patient underwent thoracotomy and resection of the mass. Histological examination of the lung mass revealed findings consistent with a de-differentiated chordoma, confirming extraneural metastasis from the original tumor without evidence of local recurrence. Chest wall and scalp metastases subsequently developed, and the patient was started on an adjuvant chemotherapy regimen that included imatinib and rapamycin followed by subsequent nivolumab and an EZH2 inhibitor for recurrent, disseminated disease. Despite this patient's remote and distant metastases, primary gross-total resection for chordoma remains a critical treatment objective, followed by proton beam radiotherapy. This case illustrates the importance of interval posttreatment imaging and the emerging potential to treat chordoma with molecularly targeted therapies.

Pleomorphic Xanthoastrocytoma with Anaplastic Features: Retrospective Case Series.

OBJECTIVE: Pleomorphic xanthoastrocytoma (PXA) is a unique meningocerebral glioma with a relatively favorable prognosis. PXA also possesses a variant with anaplastic features (aPXA), which is associated with poor outcomes. To date, few studies have examined the clinicopathologic importance of these anaplastic features. METHODS: From 1999-2012, 8 patients with aPXA were treated at the University of California, San Francisco, California, United States. Cases were reconfirmed by neuropathology, and clinical information regarding patient demographics, tumor characteristics, and treatment outcomes was assembled. Tumors were classified as aPXA according to the World Health Organization diagnostic criteria established in 2007. RESULTS: There were 5 female and 3 male patients in our cohort, ranging in age from 4-74 years at initial diagnosis. Seizure was the most common presenting symptom (50%), and the majority of tumors arose in the frontal or temporal lobes (88%). Six patients received subtotal resection (STR), and all suffered from progression despite adjuvant radiotherapy and chemotherapy. Median time to progression was 20 months, with a 1-year progression-free survival rate of 57%. Three aPXA patients expired with a median survival of 87 months. Four patients developed disseminated disease. Three of 8 (38%) showed BRAFv600 mutation. CONCLUSION: aPXA is associated with poorer clinical outcomes compared with PXA. Gross total resection should be the goal of initial treatment. It remains unclear whether adjuvant radiation and chemotherapy are able to prevent progression or dissemination. Long-term monitoring of all patients is a critical step in management due to the potential for tumors to transform into higher-grade lesions.

Surgical Management of Intracranial Neuroenteric Cysts: The UCSF Experience.

Objective Modern surgical experience with intracranial neuroenteric cysts is limited in the literature. We review our 15-year institutional experience with these rare lesions. Design Single-institution retrospective study. Setting Large North American tertiary care center. Participants Histologically confirmed cases of intracranial neuroenteric cyst from January 2000 to September 2014. Main Outcome Measures Pre- and postoperative modified Rankin Scale (mRS) scores, extent of resection, and postoperative complications are reported. Clinical presentation, imaging features, pathology, and operative approach are discussed. Results Five spinal and six intracranial neuroenteric cysts were surgically treated over a 15-year period. Median age at presentation for the intracranial cysts was 38.5 years. Mean cyst diameter was 3.8 cm. Five cysts were located in the pre-pontomedullary cistern, and one was located in the third ventricle. Gross total resection was achieved in four of the five posterior fossa cysts through a far lateral transcondylar approach. Postoperative complications included aseptic meningitis (one), transient abducens palsy (one), and pseudomeningocele requiring reoperation (three). Postoperative mRS scores improved to ≤1 by 6.5 months median follow-up. Conclusions Intracranial neuroenteric cysts are rare lesions with a variable imaging appearance. Complete surgical resection through a far lateral transcondylar approach is possible and usually results in symptom improvement or resolution.

Meningiomas of the Anterior Clinoid Process: Is It Wise to Drill Out the Optic Canal?

INTRODUCTION:  Meningiomas of the anterior clinoid process are uncommon tumors, acknowledged by most experienced surgeons to be among the most challenging meningiomas to completely remove. In this article, we summarize our institutional experience removing these uncommon and challenging skull base meningiomas. METHODS:  We analyzed the clinical outcomes of patients undergoing surgical removal of anterior at our institution over an 18-year period. We characterized the radiographic appearance of these tumors and related tumor features to symptoms and ability to obtain a gross total resection. We also analyzed visual outcomes in these patients, focusing on visual outcomes with and without optic canal unroofing. RESULTS:  We identified 29 patients with anterior clinoid meningiomas who underwent surgical resection at our institution between 1991 and 2007. The median length of follow-up was 7.5 years (range: 2.0 to 18.6 years). Similar to others, we found gross total resection was seldom safely achievable in these patients. Despite this, only 1/20 of patients undergoing subtotal resection without immediate postoperative radiosurgery experienced tumor progression. The optic canal was unroofed in 18/29 patients in this series, while in 11/29 patients it was not. Notably, all five patients experiencing visual improvement underwent optic canal unroofing, while three of four patients experiencing visual worsening did not. CONCLUSIONS:   These data provide some evidence suggesting that unroofing the optic canal in anterior clinoid meningiomas might improve visual outcomes in these patients.