Janus Kinase-2 V617F Mutation and Antiphospholipid Syndrome in Cerebral Sinus Venous Thrombosis: Natural History and Retrospective Bicenter Analysis.

Background: Cerebral sinus venous thrombosis (CSVT) is a rare neurovascular entity, usually associated with acquired or genetic hypercoagulable states. In up to 30% of the cases it remains idiopathic. Bone marrow proliferation disorders that are associated with Janus Kinase 2 V617F mutation (JAK-2) are known causes of the systemic and cerebral thrombosis-at times despite normal blood counts-for which hematologic treatment exists. However, JAK-2 prevalence in the CSVT cases is not clear. Methods: In this retrospective analysis, data of 236 patients with CSVT admitted to two tertiary centers between 2010 and 2020 were analyzed, with emphasis on laboratory and imaging data and clinical and interventional outcomes. Results: A total of 236 patients were included in the analysis. The patients' median age was 42 years and the average age was 44 years (±19 years), with 59% female patients. JAK-2 positivity rate was 18% (among 77 patients tested for the mutation). Patients with normal blood counts on presentation comprised 36% of the JAK-2 positive cases. Other hypercoagulability states were also investigated, with the antiphospholipid syndrome (APLA) showing the highest prevalence (11%) followed by other etiologies including oral contraceptive use, Factor V Leiden, prothrombin mutation, and malignancy. Selected JAK-2, APLA, and prothrombin mutation cases showed a more severe clinical course. Conclusion: JAK-2 mutation is underdiagnosed and its screening may be warranted in the cases of idiopathic CSVT, even despite normal blood counts, to allow disease-modifying treatment and blood cell count monitoring. JAK-2, APLA, and prothrombin mutation may be associated with a more complicated clinical course.

Comparison of Frame-Based Versus Frameless Image-Guided Intracranial Stereotactic Brain Biopsy: A Retrospective Analysis of Safety and Efficacy.

BACKGROUND: A definitive diagnosis of brain lesions not amenable to surgery is mainly made by stereotactic needle biopsy. The diagnostic yield and safety of the frameless versus frame-based image-guided stereotactic techniques is unclear. Our objective was to evaluate the safety and accuracy of frameless versus frame-based stereotactic brain biopsy techniques. METHODS: A total of 278 patients (153 men; mean age: 65.5 years) with intra-axial brain lesions underwent frame-based (n = 148) or frameless image-guided stereotactic brain biopsy (n = 130) using a minimally invasive twist drill technique during 2010-2016 at Sheba Medical Center. Demographic, imaging, and clinical data were retrospectively analyzed. RESULTS: The diagnostic yield (>90%) did not differ significantly between groups. Overall morbidity (6.8% vs. 8.5%), incidence of permanent neurologic deficits (2.1% vs. 1.6%), mortality rate (0.7% vs. 0.8%), and postoperative computed tomography-detected asymptomatic (14.2% vs. 16.1%) and symptomatic (2.0% vs. 1.6%) bleeding also did not differ significantly between the frame-based and frameless cohorts, respectively. The diagnostic yield and complication rates related to the biopsy technique were not significantly associated with sex, age, entry angle to the skull and skull thickness, lesion location or depth, or radiologic characteristics. Diagnostic yield was significantly associated with the mean lesion volume. Smaller lesions were less diagnostic than larger lesions in both techniques (P = 0.043 frame-based and P = 0.048 frameless). CONCLUSIONS: The frameless biopsy technique is as efficient as the frame-based brain biopsy technique with a low complication rate. Lesion volume was the only predictive factor of diagnostic yield. The minimally invasive twist drill technique is safe and efficient.

Neuro-ophthalmologic outcomes of standard versus hypo-fractionated stereotactic radiotherapy of AVPM.

BACKGROUND: Most anterior visual pathway meningiomas (AVPM) are benign and slow-growing, but these tumors may affect visual functions, including visual acuity (VA) and visual field (VF). Due to location, most are treated non-surgically by fractionated stereotactic radiotherapy (FSRT), aiming to prevent tumor progression and visual functions deterioration. Unfortunately, FSRT in itself may affect visual functions. The current preferred treatment regimen (in terms of safety and effectiveness) is undetermined. While most cases are treated with conventional fractionation (cFSRT)-50.4-54 Gy in 28-30 fractions of 1.8-2 Gy, advances in technology have allowed shortening of total treatment length to hypofractionation (hSRT)-25-27 Gy in 3-5 fractions of 5-9 Gy. Our aim was to evaluate the association of radiotherapy regimen for treating AVPM (cFSRT vs. hSRT) with visual function outcomes (VA, VF) at the last neuro-ophthalmologic evaluation. METHODS: We conducted a retrospective cohort study of AVPM cases treated at Sheba Medical Center during 2004-2015. We compared cFSRT and hSRT regimens regarding visual function (VA, VF) outcomes at the last neuro-ophthalmologic evaluation. VA was determined by the logarithm of the minimum angle of resolution (LogMAR). VF was determined by the mean deviation (MD). A clinically relevant change in VA was defined as 0.2 LogMAR. RESULTS: 48 patients (13 receiving hSRT, 35 receiving cFSRT) were included, with a median follow-up of 55 months. No significant difference was evident regarding LogMAR or MD of involved eyes at the last evaluation. Six (17%) patients in the cFSRT group experienced clinically relevant VA deterioration in the involved eye, compared with six (46%) in hSRT (p = 0.06). CONCLUSION: Our findings, using comprehensive and meticulous investigation of visual outcomes, suggest that hSRT may be associated with higher risk for VA and VF deterioration in AVPM especially in ONSM. We recommend the use of cFSRT for ONSM.

Utility of the Polestar N30 low-field MRI system for resecting non-enhancing intra-axial brain lesions.

BACKGROUND: To determine the utility of an intraoperative magnetic resonance imaging (iMRI) system, the Polestar N30, for enhancing the resection control of non-enhancing intra-axial brain lesions. MATERIALS AND METHODS: Seventy-three patients (60 males [83.3%], mean age 37 years) with intra-axial brain lesions underwent resection at Sheba Medical Centre using the Polestar between February 2012 and the end of August 2018. Demographic and imaging data were retrospectively analysed. Thirty-five patients had a non-enhancing lesion (48%). RESULTS: Complete resection was planned for 60/73 cases after preoperative imaging. Complete resection was achieved in 59/60 (98.3%) cases. After iMRI, additional resection was performed in 24/73 (32.8%) cases, and complete resection was performed in 17/60 (28.8%) cases in which a complete resection was intended. In 6/13 (46%) patients for whom incomplete resection was intended, further resection was performed. The extent of resection was extended mainly for non-enhancing lesions: 16/35 (46%) as opposed to only 8/38 (21%) for enhancing lesions. Further resection was not significantly associated with sex, age, intended resection, recurrence, or affected side. Univariate analysis revealed non-eloquent area, intended complete resection, and enhancing lesions to be predictive factors for complete resection, and non-enhancing lesions and scan time to be predictive factors for an extended resection. Non-enhancement was the only independent factor for extended resection. CONCLUSIONS: The Polestar N30 is useful for evaluating residual non-enhancing intra-axial brain lesions and achieving maximal resection.

Linear accelerator stereotactic radiosurgery can modulate the clinical course of Hemangioblastoma: Case series and review of the literature.

Hemangioblastomas (HB) are benign low grade vascular tumors most frequently occurring in the cerebellum, brain stem, and spinal cord. Often associated with Von Hippel Lindau disease (VHL), the lesions are often multifocal requiring complex resection and are difficult to control. Linear Accelerator (LINAC) Stereotactic Radiosurgery (SRS) has been demonstrated to provide additional tumor control. In this case series, we present our multi-center experience utilizing LINAC SRS in fourteen patients with 23 lesions. We observed a tumor control rate of 87% and found interval changes in the peritumoral enhancement to correlate with treatment outcome. In our study, SRS treatment was also well-tolerated in both cystic and noncystic patients with multifocal disease. Disease control was achieved in all but three patients post-resection and no longitudinal radiation-induced secondary malignancy was observed. SRS response correlated highly with lesion size and radiation dose. We conclude that LINAC SRS is safe and effective for patients with HB and should be considered in addition to surgery in asymptomatic, VHL patients, deep seated lesions and isolated lesions.

Do Not Give Up on Ossified Tuberculum Sellae Meningioma - Vision Restored.

This case report accompanies a video of the treatment of a Tuberculum sellae meningioma (TSM) in a woman that presented with left eye near-blindness. The senior author conducted the operation via a pterional retractorless approach, and the patient had a full recovery. This case report discusses the unique anatomy of conchal sphenoid sinus, ossified TSM with very calcified consistency, and retractorless brain microsurgery. The resection of ossified TSM is still safe and viable with adequate microsurgical techniques and skull base instruments without compromising the neurovascular structure and with good neurological and visual outcomes for the patient.

miR-504 modulates the stemness and mesenchymal transition of glioma stem cells and their interaction with microglia via delivery by extracellular vesicles.

Glioblastoma (GBM) is a highly aggressive tumor with poor prognosis. A small subpopulation of glioma stem cells (GSCs) has been implicated in radiation resistance and tumor recurrence. In this study we analyzed the expression of miRNAs associated with the functions of GSCs using miRNA microarray analysis of these cells compared with human neural stem cells. These analyses identified gene clusters associated with glioma cell invasiveness, axonal guidance, and TGF-ß signaling. miR-504 was significantly downregulated in GSCs compared with NSCs, its expression was lower in GBM compared with normal brain specimens and further decreased in the mesenchymal glioma subtype. Overexpression of miR-504 in GSCs inhibited their self-renewal, migration and the expression of mesenchymal markers. The inhibitory effect of miR-504 was mediated by targeting Grb10 expression which acts as an oncogene in GSCs and GBM. Overexpression of exogenous miR-504 resulted also in its delivery to cocultured microglia by GSC-secreted extracellular vesicles (EVs) and in the abrogation of the GSC-induced polarization of microglia to M2 subtype. Finally, miR-504 overexpression prolonged the survival of mice harboring GSC-derived xenografts and decreased tumor growth. In summary, we identified miRNAs and potential target networks that play a role in the stemness and mesenchymal transition of GSCs and the miR-504/Grb10 pathway as an important regulator of this process. Overexpression of miR-504 exerted antitumor effects in GSCs as well as bystander effects on the polarization of microglia via delivery by EVs.

Spinal intradural extramedullary tumors: the value of intraoperative neurophysiologic monitoring on surgical outcome.

Nerve sheath tumors and meningiomas account for most intradural extramedullary (IDEM) tumors. These tumors are benign and amenable to complete surgical resection. In recent years, these surgeries are performed with intraoperative neurophysiologic monitoring (IONM) in order to minimize neurological injury, but the evidence for the statistical efficacy of this utility is lacking. This paper evaluates IONM benefits in IDEM tumor resection. Data of patients treated surgically for spinal intradural tumors from 1998 to 2003 was previously collected and analyzed. We retrospectively evaluated patients' charts operated in the years 2011 to 2013. Patients' medical files were reviewed including radiological examinations and electrophysiological reports. The data was collected and evaluated. Forty-one cases of meningioma or nerve sheath tumor resection surgery were performed in the study period. The surgical results were compared to 70 cases of historical controls. Demographic data was similar in these two groups. Sensitivity, specificity, and positive and negative predicted values of IONM were 75, 100, 100, and 97%, respectively. New neurological deficit rate was evident in 10 and 14% for the study and control groups, respectively (not significant). While IONM predicts neurological deficits with high accuracy level, this study does not suggest that there is a significant global benefit of IONM in these cases. As reported by others, in this series, the rate of new neurological deficits in non-monitored cases is similar to the monitored cases series; hence, IONM role in preventing new neurological deficits has yet to be proven.

Uncal herniation in a fully conscious patient-The sliding uncus syndrome.

Uncal herniation is accompanied by a decreased level of consciousness. We describe a patient who remained fully alert despite the uncal herniation. The computed tomography (CT) scans allowed us to visualize the uncus and its spatial relation to the cerebral peduncle. We describe the sliding uncus syndrome.

Endoscopic endonasal transsphenoidal "above and below" approach to the retroinfundibular area and interpeduncular cistern--cadaveric study and case illustrations.

OBJECTIVE: To evaluate the feasibility of reaching the interpeduncular cistern (IC) through an endoscopic endonasal approach that leaves the pituitary gland in place. METHODS: In a series of 10 injected cadaver heads, the transtuberculum ("above") and transclival ("below") approaches were combined, without pituitary transposition. Using 0-degree, 30-degree, and 45-degree endoscopes, the extent of overlap and if a blind spot occurred were determined. Also, the visualization of the IC was compared with the transposition of the pituitary gland approach. Nonparametric statistics were used to evaluate the results. The approach was implemented in 2 patients. RESULTS: For both the "above" and "below" views, there was a statistically significant increase in field of view when comparing the 0-degree endoscope with either the 30-degree endoscope (P < 0.05) or the 45-degree endoscope (P < 0.05). There was no difference between the 30-degree endoscope and the 45-degree endoscope (P > 0.05) in the "below" approach, but there was a difference (P < 0.05) in the "above" approach. There was no blind spot with any combination of endoscopes. There was no practical statistically significant difference between the transposition approach and the "above and below" approach. The "above and below" approach was used successfully in 2 surgeries. CONCLUSIONS: It is possible to work both "above" and "below" the pituitary gland to reach the IC through an endoscopic endonasal approach. The advantages are the maintenance of normal pituitary and parasellar anatomy and the minimization of the size of the skull base defect. There is no blind spot using this approach that would be revealed with a pituitary transposition. The feasibility of this approach has been confirmed in 2 patients.

Incidence and significance of intraoperative cerebrospinal fluid leak in endoscopic pituitary surgery using intrathecal fluorescein.

OBJECTIVE: The true rate of intraoperative cerebrospinal fluid (iCSF) leak during pituitary surgery is not well known because small iCSF leaks are easily missed. Our objective is to determine the rate and significance of iCSF leak in endoscopic pituitary surgery with intrathecal (IT) fluorescein administration and determine factors predictive of iCSF leak. METHODS: IT fluorescein was administered in 203 consecutive endoscopic, endonasal pituitary surgeries. The rate of iCSF leak was noted prospectively and correlated with tumor diameter and volume, gross total resection, and the learning curve. Postoperative CSF leak rate, complications, and nasoseptal flap utility were also investigated. RESULTS: The rate of iCSF leak was 61% overall, 44% for tumors<2 cm compared to 72% for tumors≥2 cm and 35% for tumors<1.5 cm3 compared to 68% for those≥1.5 cm3 (P<0.001). Postoperative CSF leak was significantly lower after the first 50 cases (0.7% vs. 10%; P<0.005) with overall leak of 3%. For tumors>2 cm, the introduction of nasoseptal flap reduced the rate of postoperative CSF leak from 5.6% to 1.4%. We did not find any complications clearly related with the use of IT fluorescein. CONCLUSION: The rate of iCSF leak during endoscopic pituitary surgery using IT fluorescein is higher than previously reported. Tumor diameter and volume are best predictors of the risk of iCSF leak. Based on this knowledge and a closure algorithm that includes a lumbar drain and nasoseptal flap for larger tumors (>2.5 cm), we can conclude that the postoperative CSF leak rate remains exceptionally low, particularly once the learning curve is overcome.

Combined cranionasal surgery for spheno-orbital meningiomas invading the paranasal sinuses, pterygopalatine, and infratemporal fossa.

OBJECTIVE: To evaluate the efficacy of combining an endonasal endoscopic skull-base approach and repair with a transcranial orbitozygomatic approach for spheno-orbital meningiomas (SOMs). METHODS: Three patients with recurrent SOMs underwent combined orbitozygomatic and endonasal endoscopic surgery. In 2 patients both procedures were done in 1 operation and in 1 patient the endonasal surgery was done 2.5 months after the craniotomy. Extent of resection, complications, morbidity, and mortality were evaluated. RESULTS: Gross total resection was achieved in 1 patient and near total resection in the other 2 patients with tumor left in the cavernous sinus and parapharyngeal space. Two patients suffered cranial neuropathy from the transcranial surgery and the other developed a pseudomeningocele. There were no complications from the endonasal surgery. Patients having combined single setting cranionasal surgery were discharged on day 6 and 8, whereas the patient having only the endonasal component on a later date was discharged on day 2. CONCLUSIONS: A combined cranionasal approach involving transcranial orbitozygomatic and endonasal endoscopic approaches is an effective 2-stage surgery for resecting SOMs invading into the sinuses and paranasal compartments. The ability to perform a multilayer closure involving a vascularized nasoseptal flap additionally decreases the risk of postoperative cerebrospinal fluid leak.

Giant anterior clinoidal meningiomas: surgical technique and outcomes.

OBJECT: Surgery for giant anterior clinoidal meningiomas that invade vital neurovascular structures surrounding the anterior clinoid process is challenging. The authors present their skull base technique for the treatment of giant anterior clinoidal meningiomas, defined here as globular tumors with a maximum diameter of 5 cm or larger, centered around the anterior clinoid process, which is usually hyperostotic. METHODS: Between 2000 and 2010, the authors performed 23 surgeries in 22 patients with giant anterior clinoidal meningiomas. They used a skull base approach with extradural unroofing of the optic canal, extradural clinoidectomy (Dolenc technique), transdural debulking of the tumor, early optic nerve decompression, and early identification and control of key neurovascular structures. RESULTS: The mean age at surgery was 53.8 years. The mean tumor diameter was 59.2 mm (range 50-85 mm) with cavernous sinus involvement in 59.1% (13 of 22 patients). The tumor involved the prechiasmatic segment of the optic nerve in all patients, invaded the optic canal in 77.3% (17 of 22 patients), and caused visual impairment in 86.4% (19 of 22 patients). Total resection (Simpson Grade I or II) was achieved in 30.4% of surgeries (7 of 23); subtotal and partial resections were each achieved in 34.8% of surgeries (8 of 23). The main factor precluding total removal was cavernous sinus involvement. There were no deaths. The mean Glasgow Outcome Scale score was 4.8 (median 5) at a mean of 56 months of follow-up. Vision improved in 66.7% (12 of 18 patients) with consecutive neuroophthalmological examinations, was stable in 22.2% (4 of 18), and deteriorated in 11.1% (2 of 18). New deficits in cranial nerve III or IV remained after 8.7% of surgeries (2 of 23). CONCLUSIONS: This modified surgical protocol has provided both a good extent of resection and a good neurological and visual outcome in patients with giant anterior clinoidal meningiomas.

Endoscopic endonasal posterior clinoidectomy.

BACKGROUND: Posterior clinoidectomy is a useful procedure for maximizing exposure to the interpeduncular cistern via transcranial approaches for basilar tip aneurysms and select intracranial tumors. The value of posterior clinoidectomy during endonasal endoscopic transclival surgery is not well described. METHODS: We performed endoscopic endonasal transsphenoidal extradural bilateral posterior clinoidectomy and dorsum sella removal on five silicon-injected cadaveric heads. The dorsum sella was split in the midline and removed from medial to lateral until the posterior clinoids were encountered. The posterior clinoid was dissected from the medial wall of the cavernous sinus and mobilized medially in order to detach it from the ligaments and carefully fractured it from the bony attachment to the petrous apex and carotid canal. Following this, the clival and dorsum sella dura was opened to expose the interpeduncular cistern and its contents. RESULTS: The technical feasibility of endoscopic endonasal extradural posterior clinoidectomy was reproduced in all five cadaveric specimens. This technique was performed without damaging the vital structures, including preservation of the pituitary gland. After performing bilateral posterior clinoidectomy, the retrosellar dura was opened, allowing good visualization of the contents of the prepontine and interpeduncular cistern. CONCLUSION: We describe the technique of endoscopic endonasal extradural posterior clinoidectomy. We believe this approach is best suited for retrosellar pathology located in the interpeduncular cistern and is a useful adjunct to the transclival approach to increase the field of view and maximize the extent of resection.

The importance and timing of optic canal exploration and decompression during endoscopic endonasal resection of tuberculum sella and planum sphenoidale meningiomas.

BACKGROUND: Suprasellar meningiomas often invade the optic canals (OCs). The feasibility of removing these tumors through a minimal-access endonasal route has been demonstrated, but the importance, safety, and timing of OC exploration and decompression are not well described. OBJECTIVE: To create a simple decision-tree algorithm for OC exploration and decompression in the endonasal endoscopic surgery for planum sphenoidale and tuberculum sella meningiomas. METHODS: We identified a consecutive series of 8 planum sphenoidale and tuberculum sella meningiomas resected endonasally. "Late" OC exploration and decompression was performed in 4 of 8 patients. The extent of resection, visual outcome, and complications were recorded. RESULTS: Five patients had OC invasion on magnetic resonance imaging. Endoscopic inspection did not reveal additional OC invasion. The OC was opened bilaterally in 2 patients and unilaterally in 2 patients. Gross total resection was achieved in 6 of 7 patients in whom it was the goal. Vision improved in 3 patients (3 of 3 OCs opened) and was stable in 4 (1 of 4 OCs opened). In 1 patient, the bitemporal hemianopsia improved, but there was unilateral deterioration (no OC invasion) because the tumor was extremely adherent to 1 optic nerve. After an average follow-up of 20.9 months, all patients had an Glasgow Outcome Scale score of 5, and there were no cerebrospinal fluid leaks. CONCLUSION: Exploration and decompression of the OC are feasible, safe, and important to optimize visual outcome and to minimize recurrence in planum sphenoidale and tuberculum sella meningiomas resected endonasally. It may not be important to open the canal early during surgery because tumor debulking can be performed without manipulating the optic nerves. Early decompression, however, is technically feasible.

Postembolization perianeurysmal edema as a cause of uncinate seizures.

We report a patient with a giant unruptured supraclinoid aneurysm treated by endovascular embolization by means of bare coils and implantation of a flow diverterstent. Eight weeks after the embolization, she presented with uncinate seizures. Neuroradiological examination revealed de novo postembolization perianeurysmal edema, which has been described only rarely. A brief course of oral steroids successfully controlled the seizures. Perianeurysmal edema must be considered a potential complication after embolization of large aneurysms with coils and other means, and needs to be considered as a differential diagnosis in patients with unusual neurological symptoms at either the acute or delayed stages. To our knowledge, this is the first report of postembolization perianeurysmal edema occurring after successful occlusion by means of bare coils and a flow diverterstent. This report contributes to the growing evidence on adverse post-coiling inflammatory reactions, and specifically on perianeurysmal edema.

Stent-based mechanical thrombectomy in acute basilar artery occlusion.

Stent-based mechanical thrombectomy was recently proposed as an effective alternative to other mechanical techniques to achieve recanalization of large-vessel embolic occlusions in the anterior circulation. To our knowledge, there are no reports of the use of this technique in acute basilar artery occlusion (ABAO). We present a patient with complete endovascular recanalization of ABAO using a stent-based thrombectomy technique. Advantages and limitations of this technique in the management of ABAO are discussed. The stent-thrombectomy technique is promising, and will need further evaluation in posterior circulation stroke.